diff --git a/models/synSynth7.xml b/models/synSynth7.xml index 9a8a495..197d37d 100644 --- a/models/synSynth7.xml +++ b/models/synSynth7.xml @@ -1,10 +1,10 @@ - + 2000.0 - + ee 0.001 1.0 /kinetics[0]/MAPK[0]/MAPK_p_p[0]; /kinetics[0]/PKA[0]/PKA_active[0]; /kinetics[0]/CaMKII[0]/tot_CaM_CaMKII[0]; /kinetics[0]/CaMKII[0]/tot_autonomous_CaMKII[0]; /kinetics[0]/PKC[0]/PKC_active[0]; /kinetics[0]/MAPK[0]/Raf_p_GTP_Ras[0]; /kinetics[0]/MAPK[0]/craf_1_p[0]; /kinetics[0]/Ca[0]/Ca[0]; /kinetics[0]/CaM[0]/CaM_Ca4[0]; /kinetics[0]/PLCbeta[0]/DAG[0]; /kinetics[0]/PLCbeta[0]/IP3[0]; /kinetics[0]/PLA2[0]/Arachidonic_Acid[0]; /kinetics[0]/Ras[0]/GTP_Ras[0] @@ -63,90 +63,113 @@ - + + + + CubeMesh + False + + + - + 0.0 0.0 red 0 + 0.0 + 0.0 - + 14.7058823529 0.0 cyan 0 + 0.0 + 0.0 - + 29.4117647059 0.0 orange 0 + 0.0 + 0.0 - + 44.1176470588 0.0 pink 0 + 0.0 + 0.0 - + 58.8235294118 0.0 yellow 0 + 0.0 + 0.0 - + 73.5294117647 0.0 pink 0 + 0.0 + 0.0 - + 88.2352941176 0.0 cyan 0 + 0.0 + 0.0 - + 102.941176471 0.0 white 0 + 0.0 + 0.0 - + CoInit was .0624 @@ -158,20 +181,24 @@ 0.0 white 0 + 0.0 + 0.0 - + 7.35294117647 - -144.578313253 + 144.578313253 white 0 + 0.0 + 0.0 - + Marquez et al J. Immun 149,2560(92) est 1e6/cell for chromaffin cells We will use 1 uM as our initial concen @@ -180,29 +207,33 @@ 22.0588235294 - -144.578313253 + 144.578313253 white 0 + 0.0 + 0.0 - + 66.1764705882 - -144.578313253 + 144.578313253 red 0 + 0.0 + 0.0 - - - - - - - + + + + + + + Calculated cytosolic was 20 nm from Wijkander and Sundler However, Leslie and Channon use about 400 nM. Need to confirm, but this is the value I use here. Another recalc of W_andS gives 1uM @@ -214,54 +245,64 @@ 0.0 yellow 1 + 0.0 + 0.0 - + 161.764705882 0.0 yellow 1 + 0.0 + 0.0 - - + + 176.470588235 0.0 cyan 1 + 0.0 + 0.0 - - + + 191.176470588 0.0 cyan 1 + 0.0 + 0.0 - - + + 205.882352941 0.0 pink 1 + 0.0 + 0.0 - - + + arachodonylphosphatidylcholine is the favoured substrate from Wijkander and Sundler, JBC 202 pp 873-880, 1991. Their assay used 30 uM substrate, which is what the kinetics in this model are based on. For the later model we should locate a more realistic value for APC. @@ -273,10 +314,12 @@ 0.0 yellow 1 + 0.0 + 0.0 - + Phosphorylated form of PLA2. Still need to hook it up using kinases. PKA: Wightman et al JBC 257 pp6650 1982 PKC: Many refs, eg Gronich et al JBC 263 pp 16645, 1988 but see Lin etal MAPK: Lin et al, Cell 72 pp 269, 1993. Show 3x with MAPK but not PKC alone Do not know if there is a Ca requirement for active phosphorylated state. @@ -288,31 +331,37 @@ 0.0 orange 1 + 0.0 + 0.0 - - + + 250.0 0.0 orange 1 + 0.0 + 0.0 - + 154.411764706 - -144.578313253 + 144.578313253 darkgreen 1 + 0.0 + 0.0 - + Total PLC = 0.8 uM see Ryu et al JBC 262 (26) pp 12511 1987 @@ -324,31 +373,37 @@ 0.0 cyan 2 + 0.0 + 0.0 - + 308.823529412 0.0 green 2 + 0.0 + 0.0 - + 323.529411765 0.0 cyan 2 + 0.0 + 0.0 - - + + This should really be labelled PLC-G*GTP-Ca. This is the activated form of the enzyme. Mahama and Linderman assume that the IP3 precursors are not rate-limiting, but I will include those for completeness as they may be needed later. @@ -360,21 +415,25 @@ 0.0 cyan 2 + 0.0 + 0.0 - - + + 352.941176471 0.0 cyan 2 + 0.0 + 0.0 - + Phosphatidylcholine is the main (around 55%) metabolic product of DAG, follwed by PE (around 25%). Ref is Welsh and Cabot, JCB35:231-245(1987) @@ -386,20 +445,24 @@ 0.0 green 2 + 0.0 + 0.0 - + 323.529411765 - -144.578313253 + 144.578313253 green 2 + 0.0 + 0.0 - + Peak IP3 is perhaps 15 uM, basal _lessthan_= 0.2 uM. @@ -408,23 +471,27 @@ 338.235294118 - -144.578313253 + 144.578313253 pink 2 + 0.0 + 0.0 - + 382.352941176 0.0 green 2 + 0.0 + 0.0 - + I am implementing this as acting only on the Rec-Gq complex, based on a more complete model PLC_Gq48.g which showed that the binding to the rec alone contributed only a small amount. @@ -436,36 +503,42 @@ 0.0 seagreen 3 + 0.0 + 0.0 - + 455.882352941 0.0 seagreen 3 + 0.0 + 0.0 - + 588.235294118 0.0 orange 4 + 0.0 + 0.0 - - - - - - - + + + + + + + Couldn't find any ref to the actual conc of craf-1 but I should try Strom et al Oncogene 5 pp 345 In line with the other kinases in the cascade, I estimate the conc to be 0.2 uM. To init we use 0.15, which is close to equil @@ -477,22 +550,26 @@ 0.0 pink 4 + 0.0 + 0.0 - + 617.647058824 0.0 pink 4 + 0.0 + 0.0 - - - + + + Conc is from Seger et al JBC 267:20 pp14373 (1992) mwt is 45/46 Kd We assume that phosphorylation on both ser and thr is needed for activiation. See Kyriakis et al Nature 358 417 1992 Init conc of total is 0.18 @@ -504,10 +581,12 @@ 0.0 pink 4 + 0.0 + 0.0 - + conc is from Sanghera et al JBC 265 pp 52 (1990) A second calculation gives 3.1 uM, from same paper. They est MAPK is 1e-4x total protein, and protein is 15% of cell wt, so MAPK is 1.5e-5g/ml = 0.36uM. which is closer to our first estimate. Lets use this. @@ -519,10 +598,12 @@ 0.0 pink 4 + 0.0 + 0.0 - + Negative feedback by MAPK* by hyperphosphorylating craf-1* gives rise to this pool. Ueki et al JBC 269(22):15756-15761, 1994 @@ -534,10 +615,12 @@ 0.0 hotpink 4 + 0.0 + 0.0 - + Haystead et al FEBS Lett. 306(1) pp 17-22 show that phosphorylation is strictly sequential, first tyr185 then thr183. @@ -549,10 +632,12 @@ 0.0 orange 4 + 0.0 + 0.0 - + MAPKK phosphorylates MAPK on both the tyr and thr residues, first tyr then thr. Refs: Seger et al JBC267:20 pp 14373 1992 The MAPKK itself is phosphorylated on ser as well as thr residues. Let us assume that the ser goes first, and that the sequential phosphorylation is needed. See Kyriakis et al Nature 358 417-421 1992 @@ -564,12 +649,14 @@ 0.0 pink 4 + 0.0 + 0.0 - - - + + + Intermediately phophorylated, assumed inactive, form of MAPKK @@ -581,32 +668,38 @@ 0.0 pink 4 + 0.0 + 0.0 - + 595.588235294 - -144.578313253 + 144.578313253 red 4 + 0.0 + 0.0 - - - + + + 610.294117647 - -144.578313253 + 144.578313253 27 4 + 0.0 + 0.0 - + Guanine nucleotide exchange factor. This activates raf by exchanging bound GDP with GTP. I have left the GDP/GTP out of this reaction, it would be trivial to put them in. See Boguski _and McCormick. Possible candidate molecules: RasGRF, smgGDS, Vav (in dispute). rasGRF: Kcat= 1.2/min Km = 680 nM smgGDS: Kcat: 0.37 /min, Km = 220 nM. vav: Turnover up over baseline by 10X, @@ -618,11 +711,13 @@ 0.0 hotpink 5 + 0.0 + 0.0 - - + + Assume that SoS is present only at 50 nM. Revised to 100 nM to get equil to experimentally known levels. @@ -634,11 +729,13 @@ 0.0 hotpink 5 + 0.0 + 0.0 - - + + phosphorylated and thereby activated form of GEF. See, e.g. Orita et al JBC 268:34 25542-25546 1993, Gulbins et al. It is not clear whether there is major specificity for tyr or ser/thr. @@ -650,11 +747,13 @@ 0.0 hotpink 5 + 0.0 + 0.0 - - + + Only a very small fraction (7% unstim, 15% stim) of ras is GTP-bound. Gibbs et al JBC 265(33) 20437 @@ -666,10 +765,12 @@ 0.0 orange 5 + 0.0 + 0.0 - + GDP bound form. See Rosen et al Neuron 12 1207-1221 June 1994. the activation loop is based on Boguski and McCormick Nature 366 643-654 93 Assume Ras is present at about the same level as craf-1, 0.2 uM. Hallberg et al JBC 269:6 3913-3916 1994 estimate upto 5-10% of cellular Raf is assoc with Ras. Given that only 5-10% of Ras is GTP-bound, we need similar amounts of Ras as Raf. @@ -681,20 +782,24 @@ 0.0 pink 5 + 0.0 + 0.0 - + 808.823529412 0.0 red 5 + 0.0 + 0.0 - + GTPase-activating proteins. See Boguski and McCormick. Turn off Ras by helping to hydrolyze bound GTP. This one is probably NF1, ie., Neurofibromin as it is inhibited by AA and lipids, and expressed in neural cells. p120-GAP is also a possible candidate, but is less regulated. Both may exist at similar levels. See Eccleston et al JBC 268(36) pp27012-19 Level=.002 @@ -706,11 +811,13 @@ 0.0 red 5 + 0.0 + 0.0 - - + + Phosphorylation-inactivated form of GEF. See Hordijk et al JBC 269:5 3534-3538 1994 and Buregering et al EMBO J 12:11 4211-4220 1993 @@ -722,10 +829,12 @@ 0.0 hotpink 5 + 0.0 + 0.0 - + See Farnsworth et al Nature 376 524-527 1995 @@ -737,11 +846,13 @@ 0.0 pink 5 + 0.0 + 0.0 - - + + Berkers et al JBC 266 say 22K hi aff recs. Sherrill and Kyte Biochemistry 35 use range 4-200 nM. These match, lets use them. @@ -753,10 +864,12 @@ 0.0 red 6 + 0.0 + 0.0 - + This is terribly simplified: there are many interesting intermediate stages, including dimerization and assoc with adapter molecules like Shc, that contribute to the activation of the EGFR. @@ -768,43 +881,51 @@ 0.0 red 6 + 0.0 + 0.0 - - - + + + 911.764705882 0.0 red 6 + 0.0 + 0.0 - + 926.470588235 0.0 red 6 + 0.0 + 0.0 - + 0.0 - -192.771084337 + 192.771084337 brown 7 + 0.0 + 0.0 - - + + There are 2 isoforms: 52 KDa and 46 KDa (See Okada et al JBC 270:35 pp 20737 1995). They are acted up on by the EGFR in very similar ways, and apparently both bind Grb2 similarly, so we'll bundle them together here. Sasaoka et al JBC 269:51 pp 32621 1994 show immunoprecs where it looks like there is at least as much Shc as Grb2. So we'll tentatively say there is 1 uM of Shc. @@ -813,33 +934,39 @@ 14.7058823529 - -192.771084337 + 192.771084337 orange 7 + 0.0 + 0.0 - + 29.4117647059 - -192.771084337 + 192.771084337 orange 7 + 0.0 + 0.0 - + 44.1176470588 - -192.771084337 + 192.771084337 orange 7 + 0.0 + 0.0 - + There is probably a lot of it in the cell: it is also known as Ash (abundant src homology protein I think). Also Waters et al JBC 271:30 18224 1996 say that only a small fraction of cellular Grb is precipitated out when SoS is precipitated. As most of the Sos seems to be associated with Grb2, it would seem like there is a lot of the latter. Say 1 uM. I haven't been able to find a decent.... @@ -848,33 +975,39 @@ 58.8235294118 - -192.771084337 + 192.771084337 orange 7 + 0.0 + 0.0 - + 73.5294117647 - -192.771084337 + 192.771084337 orange 7 + 0.0 + 0.0 - + 88.2352941176 - -192.771084337 + 192.771084337 red 7 + 0.0 + 0.0 - + I have tried using low (0.02 uM) initial concs, but these give a very flat response to EGF stim although the overall activation of Ras is not too bad. I am reverting to 0.1 because we expect a sharp initial response, followed by a decline. Sep 17 1997: The transient activation curve looks better with [Sos] = 0.05. Apr 26 1998: Some error there, it is better where it was at 0.1 @@ -883,23 +1016,27 @@ 102.941176471 - -192.771084337 + 192.771084337 red 7 + 0.0 + 0.0 - + 117.647058824 - -192.771084337 + 192.771084337 42 7 + 0.0 + 0.0 - + Amount from Homma et al JBC 263:14 6592-6598 1988 @@ -908,54 +1045,64 @@ 147.058823529 - -192.771084337 + 192.771084337 pink 8 + 0.0 + 0.0 - + 161.764705882 - -192.771084337 + 192.771084337 pink 8 + 0.0 + 0.0 - + 176.470588235 - -192.771084337 + 192.771084337 pink 8 + 0.0 + 0.0 - + 191.176470588 - -192.771084337 + 192.771084337 pink 8 + 0.0 + 0.0 - + 205.882352941 - -192.771084337 + 192.771084337 33 8 + 0.0 + 0.0 - - + + Huge conc of CaMKII. In PSD it is 20-40% of protein, so we assume it is around 2.5% of protein in spine as a whole. This level is so high it is unlikely to matter much if we are off a bit. This comes to about 70 uM. @@ -964,23 +1111,27 @@ 294.117647059 - -192.771084337 + 192.771084337 palegreen 9 + 0.0 + 0.0 - + 308.823529412 - -192.771084337 + 192.771084337 palegreen 9 + 0.0 + 0.0 - + From Hanson and Schulman, the thr286 is responsible for autonomous activation of CaMKII. @@ -989,13 +1140,15 @@ 323.529411765 - -192.771084337 + 192.771084337 palegreen 9 + 0.0 + 0.0 - + From Hanson and Schulman, the CaMKII does a lot of autophosphorylation just after the CaM is released. This prevents further CaM binding and renders the enzyme quite independent of Ca. @@ -1004,13 +1157,15 @@ 338.235294118 - -192.771084337 + 192.771084337 cyan 9 + 0.0 + 0.0 - + I am not sure if we need to endow this one with a lot of enzs. It is likely to be a short-lived intermediate, since it will be phosphorylated further as soon as the CAM falls off. @@ -1019,13 +1174,15 @@ 352.941176471 - -192.771084337 + 192.771084337 red 9 + 0.0 + 0.0 - + This forms due to basal autophosphorylation, but I think it has to be considered as a pathway even if some CaM is floating around. In either case it will tend to block further binding of CaM, and will not display any enzyme activity. See Hanson and Schulman JBC 267:24 pp17216-17224 1992 @@ -1034,47 +1191,55 @@ 367.647058824 - -192.771084337 + 192.771084337 palegreen 9 + 0.0 + 0.0 - + 316.176470588 - -289.156626506 + 289.156626506 green 9 + 0.0 + 0.0 - - - + + + 375.0 - -289.156626506 + 289.156626506 green 9 + 0.0 + 0.0 - - - + + + 441.176470588 - -192.771084337 + 192.771084337 blue 10 + 0.0 + 0.0 - + There is a LOT of this in the cell: upto 1% of total protein mass. (Alberts et al) Say 25 uM. Meyer et al Science 256 1199-1202 1992 refer to studies saying it is comparable to CaMK levels. @@ -1083,23 +1248,27 @@ 455.882352941 - -192.771084337 + 192.771084337 pink 10 + 0.0 + 0.0 - + 470.588235294 - -192.771084337 + 192.771084337 red 10 + 0.0 + 0.0 - + The phosph form does not bind CaM (Huang et al ABB 305:2 570-580 1993) @@ -1108,13 +1277,15 @@ 485.294117647 - -192.771084337 + 192.771084337 red 10 + 0.0 + 0.0 - + Also known as RC3 and p17 and BICKS. Conc in brain _greaterthan__greaterthan_ 2 uM from Martzen and Slemmon J neurosci 64 92-100 1995 but others say less without any #s. Conc in dend spines is much higher than overall, so it could be anywhere from 2 uM to 50. We will estimate 10 uM as a starting point. Gerendasy et al JBC 269:35 22420-22426 1994 have a skeleton model (no numbers) indicating CaM-Ca(n) binding .... @@ -1123,47 +1294,55 @@ 500.0 - -192.771084337 + 192.771084337 red 10 + 0.0 + 0.0 - + 514.705882353 - -192.771084337 + 192.771084337 hotpink 10 + 0.0 + 0.0 - + 544.117647059 - -192.771084337 + 192.771084337 darkblue 10 + 0.0 + 0.0 - - - - + + + + 558.823529412 - -192.771084337 + 192.771084337 tan 10 + 0.0 + 0.0 - - + + This is the intermediate where the TR2 end (the high-affinity end) has bound the Ca but the TR1 end has not. @@ -1172,13 +1351,15 @@ 448.529411765 - -337.34939759 + 337.34939759 pink 10 + 0.0 + 0.0 - + This is the intermediate where the TR2 end (the high-affinity end) has bound the Ca but the TR1 end has not. @@ -1187,13 +1368,15 @@ 463.235294118 - -337.34939759 + 337.34939759 pink 10 + 0.0 + 0.0 - + Cohen et al Meth Enz 159 390-408 is main source of info conc = 1.8 uM @@ -1202,18 +1385,20 @@ 588.235294118 - -192.771084337 + 192.771084337 cyan 11 + 0.0 + 0.0 - - - - - - + + + + + + I1 is a 'mixed' inhibitor, but at high enz concs it looks like a non-compet inhibitor (Foulkes et al Eur J Biochem 132 309-313 9183). We treat it as non-compet, so it just turns the enz off without interacting with the binding site. Cohen et al ann rev bioch refer to results where conc is 1.5 to 1.8 uM. In order to get complete inhib of PP1, which is at 1.8 uM, we need _greaterthan_= 1.8 uM. @@ -1222,13 +1407,15 @@ 602.941176471 - -192.771084337 + 192.771084337 orange 11 + 0.0 + 0.0 - + Dephosph is mainly by PP2B @@ -1237,33 +1424,39 @@ 617.647058824 - -192.771084337 + 192.771084337 orange 11 + 0.0 + 0.0 - + 632.352941176 - -192.771084337 + 192.771084337 brown 11 + 0.0 + 0.0 - + 647.058823529 - -192.771084337 + 192.771084337 brown 11 + 0.0 + 0.0 - + We assume that the A and B subunits of PP2B are always bound under physiol conditions. Up to 1% of brain protein = 25 uM. I need to work out how it is distributed between cytosolic and particulate fractions. Tallant and Cheung '83 Biochem 22 3630-3635 have conc in many species, average for mammalian brain is around 1 uM. @@ -1272,66 +1465,78 @@ 735.294117647 - -192.771084337 + 192.771084337 tan 12 + 0.0 + 0.0 - + 750.0 - -192.771084337 + 192.771084337 tan 12 + 0.0 + 0.0 - + 764.705882353 - -192.771084337 + 192.771084337 blue 12 + 0.0 + 0.0 - + 779.411764706 - -192.771084337 + 192.771084337 blue 12 + 0.0 + 0.0 - + 794.117647059 - -192.771084337 + 192.771084337 blue 12 + 0.0 + 0.0 - + 882.352941176 - -192.771084337 + 192.771084337 yellow 13 + 0.0 + 0.0 - - - - + + + + This is the R2C2 complex, consisting of 2 catalytic (C) subunits, and the R-dimer. See Taylor et al Ann Rev Biochem 1990 59:971-1005 for a review. The Doskeland and Ogreid review is better for numbers. Amount of PKA is about .5 uM. @@ -1340,13 +1545,15 @@ 897.058823529 - -192.771084337 + 192.771084337 white 13 + 0.0 + 0.0 - + CoInit was .0624 @@ -1355,53 +1562,63 @@ 911.764705882 - -192.771084337 + 192.771084337 white 13 + 0.0 + 0.0 - + 926.470588235 - -192.771084337 + 192.771084337 white 13 + 0.0 + 0.0 - + 941.176470588 - -192.771084337 + 192.771084337 white 13 + 0.0 + 0.0 - + 955.882352941 - -192.771084337 + 192.771084337 white 13 + 0.0 + 0.0 - + 970.588235294 - -192.771084337 + 192.771084337 white 13 + 0.0 + 0.0 - + Starts at 0.15 for the test of fig 6 in Smith et al, but we aren't using that paper any more. @@ -1410,13 +1627,15 @@ 985.294117647 - -192.771084337 + 192.771084337 white 13 + 0.0 + 0.0 - + About 25% of PKA C subunit is dissociated in resting cells without having any noticable activity. Doskeland and Ogreid Int J biochem 13 pp1-19 suggest that this is because there is a corresponding amount of inhibitor protein. @@ -1425,23 +1644,27 @@ 1000.0 - -192.771084337 + 192.771084337 cyan 13 + 0.0 + 0.0 - + 889.705882353 - -337.34939759 + 337.34939759 cyan 13 + 0.0 + 0.0 - + The conc of this has been a problem. Schaecter and Benowitz use 50 uM, but Shinomura et al have _lessthan_ 5. So I have altered the cAMP-dependent rates in the PKA model to reflect this. @@ -1450,13 +1673,15 @@ 0.0 - -385.542168675 + 385.542168675 green 14 + 0.0 + 0.0 - + ATP is present in all cells between 2 and 10 mM. See Lehninger. @@ -1465,13 +1690,15 @@ 14.7058823529 - -385.542168675 + 385.542168675 red 14 + 0.0 + 0.0 - + This version of cyclase is Calmodulin activated. Gs stims it but betagamma inhibits. @@ -1480,13 +1707,15 @@ 29.4117647059 - -385.542168675 + 385.542168675 orange 14 + 0.0 + 0.0 - + Starting conc at 20 nM. @@ -1495,13 +1724,15 @@ 44.1176470588 - -385.542168675 + 385.542168675 orange 14 + 0.0 + 0.0 - + This version is activated by Gs and by a betagamma and phosphorylation. @@ -1510,23 +1741,27 @@ 58.8235294118 - -385.542168675 + 385.542168675 yellow 14 + 0.0 + 0.0 - + 73.5294117647 - -385.542168675 + 385.542168675 yellow 14 + 0.0 + 0.0 - + Starting at 0.015 uM. @@ -1535,33 +1770,39 @@ 88.2352941176 - -385.542168675 + 385.542168675 yellow 14 + 0.0 + 0.0 - + 102.941176471 - -385.542168675 + 385.542168675 orange 14 + 0.0 + 0.0 - + 117.647058824 - -385.542168675 + 385.542168675 green 14 + 0.0 + 0.0 - + The levels of the PDE are not known at this time. However, enough kinetic info and info about steady-state levels of cAMP etc are around to make it possible to estimate this. @@ -1570,14 +1811,16 @@ 7.35294117647 - -530.120481928 + 530.120481928 green 14 + 0.0 + 0.0 - - + + This form has about 2X activity as plain PDE. See Sette et al JBC 269:28 18271-18274 1994. @@ -1586,14 +1829,16 @@ 22.0588235294 - -530.120481928 + 530.120481928 green 14 + 0.0 + 0.0 - - + + CaM-Dependent PDE. Amount calculated from total rate in brain vs. specific rate. @@ -1602,14 +1847,16 @@ 36.7647058824 - -530.120481928 + 530.120481928 green 14 + 0.0 + 0.0 - - + + Activity up 6x following Ca-CaM binding. @@ -1618,24 +1865,28 @@ 51.4705882353 - -530.120481928 + 530.120481928 green 14 + 0.0 + 0.0 - - + + 66.1764705882 - -530.120481928 + 530.120481928 pink 14 + 0.0 + 0.0 - + Varying the amount of (steady state) glu between .01 uM and up, the final amount of G*GTP complex does not change much. This means that the system should be reasonably robust wr to the amount of glu in the synaptic cleft. It would be nice to know how fast it is removed. @@ -1644,13 +1895,15 @@ 147.058823529 - -385.542168675 + 385.542168675 green 15 + 0.0 + 0.0 - + From M_andL, Total # of receptors/cell = 1900 Vol of cell = 1e-15 (10 um cube). Navogadro = 6.023e23 so conversion from n to conc in uM is n/vol*nA * 1e3 = 1.66e-6 However, for typical synaptic channels the density is likely to be very high at the synapse. Use an estimate of 0.1 uM for now. this gives a total of about 60K receptors/cell, which is in line with Fay et at. @@ -1659,13 +1912,15 @@ 161.764705882 - -385.542168675 + 385.542168675 green 15 + 0.0 + 0.0 - + This acts like an enzyme to activate the g proteins Assume cell has vol 1e-15 m^3 (10 uM cube), conversion factor to conc in uM is 6e5 @@ -1674,13 +1929,15 @@ 176.470588235 - -385.542168675 + 385.542168675 green 15 + 0.0 + 0.0 - + Fraction of Rec-Gq is 44% of rec, from Fay et al. Since this is not the same receptor, this value is a bit doubtful. Still, we adjust the rate consts in Rec-bind-Gq to match. @@ -1689,23 +1946,27 @@ 191.176470588 - -385.542168675 + 385.542168675 green 15 + 0.0 + 0.0 - + 205.882352941 - -385.542168675 + 385.542168675 orange 15 + 0.0 + 0.0 - + These exist in a nebulous sense in this model, basically only to balance the conservation equations. The details of their reassociation with G-GDP are not modeled Resting level =0.0094, stim level =.0236 from all42.g ish. @@ -1714,13 +1975,15 @@ 294.117647059 - -385.542168675 + 385.542168675 yellow 16 + 0.0 + 0.0 - + Activated G protein. Berstein et al indicate that about 20-40% of the total Gq alpha should bind GTP at steady stim. This sim gives more like 65%. @@ -1729,23 +1992,27 @@ 308.823529412 - -385.542168675 + 385.542168675 red 16 + 0.0 + 0.0 - + 323.529411765 - -385.542168675 + 385.542168675 yellow 16 + 0.0 + 0.0 - + From M_andL, total Gprot = 1e5molecules/cell At equil, 92340 are here, 400 are in G*GTP, and another 600 are assoc with the PLC and 6475 are as G*GDP. This is OK. From Pang and Sternweis JBC 265:30 18707-12 1990 we get conc est 1.6 uM to 0.8 uM. A number of other factors are involved too. @@ -1754,23 +2021,27 @@ 338.235294118 - -385.542168675 + 385.542168675 yellow 16 + 0.0 + 0.0 - + 352.941176471 - -385.542168675 + 385.542168675 red 16 + 0.0 + 0.0 - + MKP-1 dephosphoryates and inactivates MAPK in vivo: Sun et al Cell 75 487-493 1993. Levels of MKP-1 are regulated, and rise in 1 hour. Kinetics from Charles et al PNAS 90:5292-5296 1993. They refer to Charles et al Oncogene 7 187-190 who show that half-life of MKP1/3CH134 is 40 min. 80% deph of MAPK in 20 min Sep 17 1997: CoInit now 0.4x to 0.0032. See parm searches from jun96 on. @@ -1779,15 +2050,17 @@ 441.176470588 - -385.542168675 + 385.542168675 hotpink 17 + 0.0 + 0.0 - - - + + + Refs: Pato et al Biochem J 293:35-41(93); Takai_andMieskes Biochem J 275:233-239 k1=1.46e-4, k2=1000,k3=250. these use kcat values for calponin. Also, units of kcat may be in min! revert to Vmax base: k3=6, k2=25,k1=3.3e-6 or 6,6,1e-6 CoInit assumed 0.1 uM. See NOTES for MAPK_Ras50.g. CoInit now 0.08 Sep 17 1997: Raise CoInt 1.4x to 0.224, see parm searches from jun 96 on. @@ -1796,51 +2069,57 @@ 455.882352941 - -385.542168675 + 385.542168675 hotpink 17 + 0.0 + 0.0 - - - - - - + + + + + + 470.588235294 - -385.542168675 + 385.542168675 red 17 + 0.0 + 0.0 - - - - - - - - - - - - - - + + + + + + + + + + + + + + 588.235294118 - -385.542168675 + 385.542168675 red 18 + 0.0 + 0.0 - + This isn't explicitly present in the M_andL model, but is obviously needed. I assume its conc is fixed at 1uM for now, which is a bit high. PLA2 is stim 7x by PIP2 @ 0.5 uM (Leslie and Channon BBA 1045:261(1990) Leslie and Channon say PIP2 is present at 0.1 - 0.2mol% range in membs, which comes to 50 nM. Ref is Majerus et al Cell 37 pp 701-703 1984 Lets use a lower level of 30 nM, same ref.... @@ -1849,150 +2128,178 @@ 735.294117647 - -385.542168675 + 385.542168675 green 19 + 0.0 + 0.0 - + 779.411764706 - -385.542168675 + 385.542168675 43 19 + 0.0 + 0.0 - + 794.117647059 - -385.542168675 + 385.542168675 37 19 + 0.0 + 0.0 - - + + 808.823529412 - -385.542168675 + 385.542168675 brown 19 + 0.0 + 0.0 - - + + 823.529411765 - -385.542168675 + 385.542168675 cyan 19 + 0.0 + 0.0 - + 838.235294118 - -385.542168675 + 385.542168675 10 19 + 0.0 + 0.0 - - + + 852.941176471 - -385.542168675 + 385.542168675 44 19 + 0.0 + 0.0 - + 742.647058824 - -530.120481928 + 530.120481928 50 19 + 0.0 + 0.0 - + 757.352941176 - -530.120481928 + 530.120481928 37 19 + 0.0 + 0.0 - - + + 794.117647059 - -530.120481928 + 530.120481928 31 19 + 0.0 + 0.0 - - + + 882.352941176 - -385.542168675 + 385.542168675 53 20 + 0.0 + 0.0 - + 897.058823529 - -385.542168675 + 385.542168675 9 20 + 0.0 + 0.0 - - + + 911.764705882 - -385.542168675 + 385.542168675 39 20 + 0.0 + 0.0 - - + + 926.470588235 - -385.542168675 + 385.542168675 60 20 + 0.0 + 0.0 - + aaa @@ -2001,234 +2308,278 @@ 941.176470588 - -385.542168675 + 385.542168675 25 20 + 0.0 + 0.0 - - - + + + 955.882352941 - -385.542168675 + 385.542168675 4 20 + 0.0 + 0.0 - + 0.0 - -578.313253012 + 578.313253012 yellow 21 + 0.0 + 0.0 - + 14.7058823529 - -578.313253012 + 578.313253012 3 21 + 0.0 + 0.0 - + 29.4117647059 - -578.313253012 + 578.313253012 38 21 + 0.0 + 0.0 - + 44.1176470588 - -578.313253012 + 578.313253012 45 21 + 0.0 + 0.0 - + 58.8235294118 - -578.313253012 + 578.313253012 red 21 + 0.0 + 0.0 - - - + + + 147.058823529 - -578.313253012 + 578.313253012 28 22 + 0.0 + 0.0 - + 161.764705882 - -578.313253012 + 578.313253012 39 22 + 0.0 + 0.0 - + 176.470588235 - -578.313253012 + 578.313253012 25 22 + 0.0 + 0.0 - + 191.176470588 - -578.313253012 + 578.313253012 44 22 + 0.0 + 0.0 - - - - + + + + 294.117647059 - -578.313253012 + 578.313253012 46 23 + 0.0 + 0.0 - + 308.823529412 - -578.313253012 + 578.313253012 Pink 23 + 0.0 + 0.0 - + 323.529411765 - -578.313253012 + 578.313253012 48 23 + 0.0 + 0.0 - - + + 338.235294118 - -578.313253012 + 578.313253012 6 23 + 0.0 + 0.0 - - - + + + 352.941176471 - -578.313253012 + 578.313253012 45 23 + 0.0 + 0.0 - - + + 441.176470588 - -578.313253012 + 578.313253012 47 24 + 0.0 + 0.0 - + 455.882352941 - -578.313253012 + 578.313253012 59 24 + 0.0 + 0.0 - + 470.588235294 - -578.313253012 + 578.313253012 52 24 + 0.0 + 0.0 - + 485.294117647 - -578.313253012 + 578.313253012 56 24 + 0.0 + 0.0 - + 500.0 - -578.313253012 + 578.313253012 39 24 + 0.0 + 0.0 - + 514.705882353 - -578.313253012 + 578.313253012 60 24 + 0.0 + 0.0 - + Q.R= Quaternary complex.Ribosome @@ -2237,23 +2588,27 @@ 588.235294118 - -578.313253012 + 578.313253012 blue 25 + 0.0 + 0.0 - + 602.941176471 - -578.313253012 + 578.313253012 pink 25 + 0.0 + 0.0 - + Q= Quaternary complex @@ -2262,13 +2617,15 @@ 617.647058824 - -578.313253012 + 578.313253012 28 25 + 0.0 + 0.0 - + 40S_complex consist of Quaternary complex, mRNA complex, 40S Ribosomes. @@ -2277,267 +2634,319 @@ 632.352941176 - -578.313253012 + 578.313253012 hotpink 25 + 0.0 + 0.0 - + 735.294117647 - -578.313253012 + 578.313253012 cyan 26 + 0.0 + 0.0 - + 750.0 - -578.313253012 + 578.313253012 brown 26 + 0.0 + 0.0 - + 764.705882353 - -578.313253012 + 578.313253012 white 26 + 0.0 + 0.0 - + 779.411764706 - -578.313253012 + 578.313253012 red 26 + 0.0 + 0.0 - + 794.117647059 - -578.313253012 + 578.313253012 45 26 + 0.0 + 0.0 - + 808.823529412 - -578.313253012 + 578.313253012 1 26 + 0.0 + 0.0 - + 823.529411765 - -578.313253012 + 578.313253012 47 26 + 0.0 + 0.0 - + 838.235294118 - -578.313253012 + 578.313253012 2 26 + 0.0 + 0.0 - + 882.352941176 - -578.313253012 + 578.313253012 44 27 + 0.0 + 0.0 - + 0.0 - -771.084337349 + 771.084337349 32 28 + 0.0 + 0.0 - + 14.7058823529 - -771.084337349 + 771.084337349 58 28 + 0.0 + 0.0 - - + + 29.4117647059 - -771.084337349 + 771.084337349 45 28 + 0.0 + 0.0 - - + + 44.1176470588 - -771.084337349 + 771.084337349 57 28 + 0.0 + 0.0 - + 147.058823529 - -771.084337349 + 771.084337349 42 29 + 0.0 + 0.0 - + 161.764705882 - -771.084337349 + 771.084337349 cyan 29 + 0.0 + 0.0 - + 176.470588235 - -771.084337349 + 771.084337349 pink 29 + 0.0 + 0.0 - + 191.176470588 - -771.084337349 + 771.084337349 21 29 + 0.0 + 0.0 - + 205.882352941 - -771.084337349 + 771.084337349 6 29 + 0.0 + 0.0 - + 220.588235294 - -771.084337349 + 771.084337349 60 29 + 0.0 + 0.0 - + 235.294117647 - -771.084337349 + 771.084337349 59 29 + 0.0 + 0.0 - + 294.117647059 - -771.084337349 + 771.084337349 27 30 + 0.0 + 0.0 - + 308.823529412 - -771.084337349 + 771.084337349 white 30 + 0.0 + 0.0 - + 323.529411765 - -771.084337349 + 771.084337349 46 30 + 0.0 + 0.0 - + 338.235294118 - -771.084337349 + 771.084337349 52 30 + 0.0 + 0.0 - - - + + + 352.941176471 - -771.084337349 + 771.084337349 blue 30 + 0.0 + 0.0 - + It will contribute to mTOR independent translation. @@ -2546,15 +2955,17 @@ 367.647058824 - -771.084337349 + 771.084337349 53 30 + 0.0 + 0.0 - - - + + + Inactivated form of S6K @@ -2563,13 +2974,15 @@ 441.176470588 - -771.084337349 + 771.084337349 3 31 + 0.0 + 0.0 - + Activated form of S6 @@ -2578,96 +2991,114 @@ 455.882352941 - -771.084337349 + 771.084337349 7 31 + 0.0 + 0.0 - + 470.588235294 - -771.084337349 + 771.084337349 44 31 + 0.0 + 0.0 - - + + 588.235294118 - -771.084337349 + 771.084337349 40 32 + 0.0 + 0.0 - + 602.941176471 - -771.084337349 + 771.084337349 51 32 + 0.0 + 0.0 - - + + 735.294117647 - -771.084337349 + 771.084337349 45 33 + 0.0 + 0.0 - + 750.0 - -771.084337349 + 771.084337349 61 33 + 0.0 + 0.0 - + 764.705882353 - -771.084337349 + 771.084337349 46 33 + 0.0 + 0.0 - + 779.411764706 - -771.084337349 + 771.084337349 52 33 + 0.0 + 0.0 - + 794.117647059 - -771.084337349 + 771.084337349 59 33 + 0.0 + 0.0 - - + + Bychkov et al., 2011. 150ng/mg *0.5mg/ml /65000g/mol = 1.155385nM (which is too low, therefore increasing the concentration arbitrarily by 1000 fold) @@ -2676,24 +3107,28 @@ 882.352941176 - -771.084337349 + 771.084337349 42 34 + 0.0 + 0.0 - - + + 897.058823529 - -771.084337349 + 771.084337349 24 34 + 0.0 + 0.0 - + Bychkov et al., 2011. 30ng/mg *0.5mg/ml /40000g/mol = 0.375nM (which is too low, therefore increasing the concentration arbitrarily by 1000 fold) @@ -2702,108 +3137,120 @@ 911.764705882 - -771.084337349 + 771.084337349 19 34 + 0.0 + 0.0 - + 926.470588235 - -771.084337349 + 771.084337349 0 34 + 0.0 + 0.0 - + 941.176470588 - -771.084337349 + 771.084337349 53 34 + 0.0 + 0.0 - + 955.882352941 - -771.084337349 + 771.084337349 61 34 + 0.0 + 0.0 - + 970.588235294 - -771.084337349 + 771.084337349 39 34 + 0.0 + 0.0 - + 985.294117647 - -771.084337349 + 771.084337349 50 34 + 0.0 + 0.0 - + - PKC_DAG_AA_p_489_0_ - PKC_Ca_memb_p_493_0_ - PKC_Ca_AA_p_491_0_ - PKC_DAG_memb_p_495_0_ - PKC_basal_p_497_0_ - PKC_AA_p_499_0_ + PKC_DAG_AA_p_462_0_ + PKC_Ca_memb_p_466_0_ + PKC_Ca_AA_p_464_0_ + PKC_DAG_memb_p_468_0_ + PKC_basal_p_470_0_ + PKC_AA_p_472_0_ - + - CaMKII_CaM_843_0_ - CaMKII_thr286_p_CaM_845_0_ + CaMKII_CaM_816_0_ + CaMKII_thr286_p_CaM_818_0_ - + - CaMKII_thr286_849_0_ - CaMKII_p_p_p_847_0_ + CaMKII_thr286_822_0_ + CaMKII_p_p_p_820_0_ - + - CaMCa4_CaNAB_964_0_ - CaMCa3_CaNAB_960_0_ - CaMCa2_CaNAB_962_0_ + CaMCa4_CaNAB_937_0_ + CaMCa3_CaNAB_933_0_ + CaMCa2_CaNAB_935_0_ - + Need est of rate of assoc of Ca and PKC. Assume it is fast The original parameter-searched kf of 439.4 has been scaled by 1/6e8 to account for change of units to n. Kf now 8.16e-7, kb=.6085 Raised kf to 1e-6 to match Ca curve, kb to .5 @@ -2812,22 +3259,22 @@ 7.35294117647 - -19.2771084337 + 19.2771084337 white 0 - - + + - + - kinetics_479_0_ * PKC_act_by_Ca_529_0__Kf * PKC_cytosolic_507_0_*Ca_1197_0_-kinetics_479_0_ * PKC_act_by_Ca_529_0__Kb * PKC_Ca_487_0_ + kinetics_451_0_ * PKC_act_by_Ca_502_0__Kf * PKC_cytosolic_480_0_*Ca_1170_0_-kinetics_451_0_ * PKC_act_by_Ca_502_0__Kb * PKC_Ca_460_0_ @@ -2835,26 +3282,26 @@ - kinetics_479_0_ - PKC_act_by_Ca_529_0__Kf - PKC_cytosolic_507_0_ - Ca_1197_0_ + kinetics_451_0_ + PKC_act_by_Ca_502_0__Kf + PKC_cytosolic_480_0_ + Ca_1170_0_ - kinetics_479_0_ - PKC_act_by_Ca_529_0__Kb - PKC_Ca_487_0_ + kinetics_451_0_ + PKC_act_by_Ca_502_0__Kb + PKC_Ca_460_0_ - - + + - + Need est of rate. Assume it is fast Obtained from param search kf raised 10 X : see Shinomura et al PNAS 88 5149-5153 1991. kf changed from 3.865e-7 to 2.0e-7 in line with closer analysis of Shinomura data. 26 June 1996: Corrected DAG data: reduce kf 15x from 2e-7 to 1.333e-8 @@ -2863,22 +3310,22 @@ 22.0588235294 - -19.2771084337 + 19.2771084337 white 0 - - + + - + - kinetics_479_0_ * PKC_act_by_DAG_531_0__Kf * DAG_632_0_*PKC_Ca_487_0_-kinetics_479_0_ * PKC_act_by_DAG_531_0__Kb * PKC_Ca_DAG_501_0_ + kinetics_451_0_ * PKC_act_by_DAG_504_0__Kf * PKC_Ca_460_0_*DAG_605_0_-kinetics_451_0_ * PKC_act_by_DAG_504_0__Kb * PKC_Ca_DAG_474_0_ @@ -2886,44 +3333,44 @@ - kinetics_479_0_ - PKC_act_by_DAG_531_0__Kf - DAG_632_0_ - PKC_Ca_487_0_ + kinetics_451_0_ + PKC_act_by_DAG_504_0__Kf + PKC_Ca_460_0_ + DAG_605_0_ - kinetics_479_0_ - PKC_act_by_DAG_531_0__Kb - PKC_Ca_DAG_501_0_ + kinetics_451_0_ + PKC_act_by_DAG_504_0__Kb + PKC_Ca_DAG_474_0_ - - + + - + 36.7647058824 - -19.2771084337 + 19.2771084337 white 0 - + - + - kinetics_479_0_ * PKC_Ca_to_memb_533_0__Kf * PKC_Ca_487_0_-kinetics_479_0_ * PKC_Ca_to_memb_533_0__Kb * PKC_Ca_memb_p_493_0_ + kinetics_451_0_ * PKC_Ca_to_memb_506_0__Kf * PKC_Ca_460_0_-kinetics_451_0_ * PKC_Ca_to_memb_506_0__Kb * PKC_Ca_memb_p_466_0_ @@ -2931,25 +3378,25 @@ - kinetics_479_0_ - PKC_Ca_to_memb_533_0__Kf - PKC_Ca_487_0_ + kinetics_451_0_ + PKC_Ca_to_memb_506_0__Kf + PKC_Ca_460_0_ - kinetics_479_0_ - PKC_Ca_to_memb_533_0__Kb - PKC_Ca_memb_p_493_0_ + kinetics_451_0_ + PKC_Ca_to_memb_506_0__Kb + PKC_Ca_memb_p_466_0_ - - + + - + Raise kb from .087 to 0.1 to match data from Shinomura et al. Lower kf from 1.155 to 1.0 to match data from Shinomura et al. @@ -2958,21 +3405,21 @@ 51.4705882353 - -19.2771084337 + 19.2771084337 white 0 - + - + - kinetics_479_0_ * PKC_DAG_to_memb_535_0__Kf * PKC_Ca_DAG_501_0_-kinetics_479_0_ * PKC_DAG_to_memb_535_0__Kb * PKC_DAG_memb_p_495_0_ + kinetics_451_0_ * PKC_DAG_to_memb_508_0__Kf * PKC_Ca_DAG_474_0_-kinetics_451_0_ * PKC_DAG_to_memb_508_0__Kb * PKC_DAG_memb_p_468_0_ @@ -2980,25 +3427,25 @@ - kinetics_479_0_ - PKC_DAG_to_memb_535_0__Kf - PKC_Ca_DAG_501_0_ + kinetics_451_0_ + PKC_DAG_to_memb_508_0__Kf + PKC_Ca_DAG_474_0_ - kinetics_479_0_ - PKC_DAG_to_memb_535_0__Kb - PKC_DAG_memb_p_495_0_ + kinetics_451_0_ + PKC_DAG_to_memb_508_0__Kb + PKC_DAG_memb_p_468_0_ - - + + - + Schaechter and Benowitz We have to increase Kf for conc scaling Changed kf to 2e-9 on Sept 19, 94. This gives better match. @@ -3007,22 +3454,22 @@ 66.1764705882 - -19.2771084337 + 19.2771084337 white 0 - - + + - + - kinetics_479_0_ * PKC_act_by_Ca_AA_537_0__Kf * Arachidonic_Acid_596_0_*PKC_Ca_487_0_-kinetics_479_0_ * PKC_act_by_Ca_AA_537_0__Kb * PKC_Ca_AA_p_491_0_ + kinetics_451_0_ * PKC_act_by_Ca_AA_510_0__Kf * Arachidonic_Acid_569_0_*PKC_Ca_460_0_-kinetics_451_0_ * PKC_act_by_Ca_AA_510_0__Kb * PKC_Ca_AA_p_464_0_ @@ -3030,26 +3477,26 @@ - kinetics_479_0_ - PKC_act_by_Ca_AA_537_0__Kf - Arachidonic_Acid_596_0_ - PKC_Ca_487_0_ + kinetics_451_0_ + PKC_act_by_Ca_AA_510_0__Kf + Arachidonic_Acid_569_0_ + PKC_Ca_460_0_ - kinetics_479_0_ - PKC_act_by_Ca_AA_537_0__Kb - PKC_Ca_AA_p_491_0_ + kinetics_451_0_ + PKC_act_by_Ca_AA_510_0__Kb + PKC_Ca_AA_p_464_0_ - - + + - + Assume slowish too. Schaechter and Benowitz @@ -3058,21 +3505,21 @@ 80.8823529412 - -19.2771084337 + 19.2771084337 white 0 - + - + - kinetics_479_0_ * PKC_act_by_DAG_AA_539_0__Kf * PKC_DAG_AA_505_0_-kinetics_479_0_ * PKC_act_by_DAG_AA_539_0__Kb * PKC_DAG_AA_p_489_0_ + kinetics_451_0_ * PKC_act_by_DAG_AA_512_0__Kf * PKC_DAG_AA_478_0_-kinetics_451_0_ * PKC_act_by_DAG_AA_512_0__Kb * PKC_DAG_AA_p_462_0_ @@ -3080,25 +3527,25 @@ - kinetics_479_0_ - PKC_act_by_DAG_AA_539_0__Kf - PKC_DAG_AA_505_0_ + kinetics_451_0_ + PKC_act_by_DAG_AA_512_0__Kf + PKC_DAG_AA_478_0_ - kinetics_479_0_ - PKC_act_by_DAG_AA_539_0__Kb - PKC_DAG_AA_p_489_0_ + kinetics_451_0_ + PKC_act_by_DAG_AA_512_0__Kb + PKC_DAG_AA_p_462_0_ - - + + - + Initial basal levels were set by kf = 1, kb = 20. In model, though, the basal levels of PKC activity are higher. @@ -3107,21 +3554,21 @@ 95.5882352941 - -19.2771084337 + 19.2771084337 white 0 - + - + - kinetics_479_0_ * PKC_basal_act_541_0__Kf * PKC_cytosolic_507_0_-kinetics_479_0_ * PKC_basal_act_541_0__Kb * PKC_basal_p_497_0_ + kinetics_451_0_ * PKC_basal_act_514_0__Kf * PKC_cytosolic_480_0_-kinetics_451_0_ * PKC_basal_act_514_0__Kb * PKC_basal_p_470_0_ @@ -3129,25 +3576,25 @@ - kinetics_479_0_ - PKC_basal_act_541_0__Kf - PKC_cytosolic_507_0_ + kinetics_451_0_ + PKC_basal_act_514_0__Kf + PKC_cytosolic_480_0_ - kinetics_479_0_ - PKC_basal_act_541_0__Kb - PKC_basal_p_497_0_ + kinetics_451_0_ + PKC_basal_act_514_0__Kb + PKC_basal_p_470_0_ - - + + - + Raise kf from 1.667e-10 to 2e-10 to get better match to data. @@ -3156,22 +3603,22 @@ 110.294117647 - -19.2771084337 + 19.2771084337 white 0 - - + + - + - kinetics_479_0_ * PKC_act_by_AA_543_0__Kf * PKC_cytosolic_507_0_*Arachidonic_Acid_596_0_-kinetics_479_0_ * PKC_act_by_AA_543_0__Kb * PKC_AA_p_499_0_ + kinetics_451_0_ * PKC_act_by_AA_516_0__Kf * PKC_cytosolic_480_0_*Arachidonic_Acid_569_0_-kinetics_451_0_ * PKC_act_by_AA_516_0__Kb * PKC_AA_p_472_0_ @@ -3179,26 +3626,26 @@ - kinetics_479_0_ - PKC_act_by_AA_543_0__Kf - PKC_cytosolic_507_0_ - Arachidonic_Acid_596_0_ + kinetics_451_0_ + PKC_act_by_AA_516_0__Kf + PKC_cytosolic_480_0_ + Arachidonic_Acid_569_0_ - kinetics_479_0_ - PKC_act_by_AA_543_0__Kb - PKC_AA_p_499_0_ + kinetics_451_0_ + PKC_act_by_AA_516_0__Kb + PKC_AA_p_472_0_ - - + + - + kf raised 10 X based on Shinomura et al PNAS 88 5149-5153 1991 closer analysis of Shinomura et al: kf now 1e-8 (was 1.66e-8). Further tweak. To get sufficient AA synergy, increase kf to 1.5e-8 26 June 1996: Corrected DAG levels: reduce kf by 15x from 1.5e-8 to 1e-9 @@ -3207,22 +3654,22 @@ 125.0 - -19.2771084337 + 19.2771084337 white 0 - - + + - + - kinetics_479_0_ * PKC_n_DAG_545_0__Kf * DAG_632_0_*PKC_cytosolic_507_0_-kinetics_479_0_ * PKC_n_DAG_545_0__Kb * PKC_DAG_503_0_ + kinetics_451_0_ * PKC_n_DAG_518_0__Kf * PKC_cytosolic_480_0_*DAG_605_0_-kinetics_451_0_ * PKC_n_DAG_518_0__Kb * PKC_DAG_476_0_ @@ -3230,26 +3677,26 @@ - kinetics_479_0_ - PKC_n_DAG_545_0__Kf - DAG_632_0_ - PKC_cytosolic_507_0_ + kinetics_451_0_ + PKC_n_DAG_518_0__Kf + PKC_cytosolic_480_0_ + DAG_605_0_ - kinetics_479_0_ - PKC_n_DAG_545_0__Kb - PKC_DAG_503_0_ + kinetics_451_0_ + PKC_n_DAG_518_0__Kb + PKC_DAG_476_0_ - - + + - + Reduced kf to 0.66X to match Shinomura et al data. Initial: kf = 3.3333e-9 New: 2e-9 Newer: 2e-8 kb was 0.2 now 2. @@ -3258,22 +3705,22 @@ 14.7058823529 - -125.301204819 + 125.301204819 white 0 - - + + - + - kinetics_479_0_ * PKC_n_DAG_AA_547_0__Kf * Arachidonic_Acid_596_0_*PKC_DAG_503_0_-kinetics_479_0_ * PKC_n_DAG_AA_547_0__Kb * PKC_DAG_AA_505_0_ + kinetics_451_0_ * PKC_n_DAG_AA_520_0__Kf * Arachidonic_Acid_569_0_*PKC_DAG_476_0_-kinetics_451_0_ * PKC_n_DAG_AA_520_0__Kb * PKC_DAG_AA_478_0_ @@ -3281,26 +3728,26 @@ - kinetics_479_0_ - PKC_n_DAG_AA_547_0__Kf - Arachidonic_Acid_596_0_ - PKC_DAG_503_0_ + kinetics_451_0_ + PKC_n_DAG_AA_520_0__Kf + Arachidonic_Acid_569_0_ + PKC_DAG_476_0_ - kinetics_479_0_ - PKC_n_DAG_AA_547_0__Kb - PKC_DAG_AA_505_0_ + kinetics_451_0_ + PKC_n_DAG_AA_520_0__Kb + PKC_DAG_AA_478_0_ - - + + - + Leslie and Channon BBA 1045 (1990) 261-270 fig6 pp267. @@ -3309,22 +3756,22 @@ 154.411764706 - -19.2771084337 + 19.2771084337 white 1 - - + + - + - kinetics_479_0_ * PLA2_Ca_act_582_0__Kf * Ca_1197_0_*PLA2_cytosolic_551_0_-kinetics_479_0_ * PLA2_Ca_act_582_0__Kb * PLA2_Ca_p_553_0_ + kinetics_451_0_ * PLA2_Ca_act_555_0__Kf * Ca_1170_0_*PLA2_cytosolic_524_0_-kinetics_451_0_ * PLA2_Ca_act_555_0__Kb * PLA2_Ca_p_526_0_ @@ -3332,45 +3779,45 @@ - kinetics_479_0_ - PLA2_Ca_act_582_0__Kf - Ca_1197_0_ - PLA2_cytosolic_551_0_ + kinetics_451_0_ + PLA2_Ca_act_555_0__Kf + Ca_1170_0_ + PLA2_cytosolic_524_0_ - kinetics_479_0_ - PLA2_Ca_act_582_0__Kb - PLA2_Ca_p_553_0_ + kinetics_451_0_ + PLA2_Ca_act_555_0__Kb + PLA2_Ca_p_526_0_ - - + + - + 169.117647059 - -19.2771084337 + 19.2771084337 white 1 - - + + - + - kinetics_479_0_ * PIP2_PLA2_act_584_0__Kf * temp_PIP2_1201_0_*PLA2_cytosolic_551_0_-kinetics_479_0_ * PIP2_PLA2_act_584_0__Kb * PIP2_PLA2_p_558_0_ + kinetics_451_0_ * PIP2_PLA2_act_557_0__Kf * PLA2_cytosolic_524_0_*temp_PIP2_1174_0_-kinetics_451_0_ * PIP2_PLA2_act_557_0__Kb * PIP2_PLA2_p_531_0_ @@ -3378,45 +3825,45 @@ - kinetics_479_0_ - PIP2_PLA2_act_584_0__Kf - temp_PIP2_1201_0_ - PLA2_cytosolic_551_0_ + kinetics_451_0_ + PIP2_PLA2_act_557_0__Kf + PLA2_cytosolic_524_0_ + temp_PIP2_1174_0_ - kinetics_479_0_ - PIP2_PLA2_act_584_0__Kb - PIP2_PLA2_p_558_0_ + kinetics_451_0_ + PIP2_PLA2_act_557_0__Kb + PIP2_PLA2_p_531_0_ - - + + - + 183.823529412 - -19.2771084337 + 19.2771084337 white 1 - - + + - + - kinetics_479_0_ * PIP2_Ca_PLA2_act_586_0__Kf * PLA2_Ca_p_553_0_*temp_PIP2_1201_0_-kinetics_479_0_ * PIP2_Ca_PLA2_act_586_0__Kb * PIP2_Ca_PLA2_p_563_0_ + kinetics_451_0_ * PIP2_Ca_PLA2_act_559_0__Kf * temp_PIP2_1174_0_*PLA2_Ca_p_526_0_-kinetics_451_0_ * PIP2_Ca_PLA2_act_559_0__Kb * PIP2_Ca_PLA2_p_536_0_ @@ -3424,26 +3871,26 @@ - kinetics_479_0_ - PIP2_Ca_PLA2_act_586_0__Kf - PLA2_Ca_p_553_0_ - temp_PIP2_1201_0_ + kinetics_451_0_ + PIP2_Ca_PLA2_act_559_0__Kf + temp_PIP2_1174_0_ + PLA2_Ca_p_526_0_ - kinetics_479_0_ - PIP2_Ca_PLA2_act_586_0__Kb - PIP2_Ca_PLA2_p_563_0_ + kinetics_451_0_ + PIP2_Ca_PLA2_act_559_0__Kb + PIP2_Ca_PLA2_p_536_0_ - - + + - + 27 June 1996 Scaled kf down by 0.015 from 3.33e-7 to 5e-9 to fit with revised DAG estimates and use of mole-fraction to calculate eff on PLA2. @@ -3452,22 +3899,22 @@ 198.529411765 - -19.2771084337 + 19.2771084337 white 1 - - + + - + - kinetics_479_0_ * DAG_Ca_PLA2_act_588_0__Kf * DAG_632_0_*PLA2_Ca_p_553_0_-kinetics_479_0_ * DAG_Ca_PLA2_act_588_0__Kb * DAG_Ca_PLA2_p_568_0_ + kinetics_451_0_ * DAG_Ca_PLA2_act_561_0__Kf * DAG_605_0_*PLA2_Ca_p_526_0_-kinetics_451_0_ * DAG_Ca_PLA2_act_561_0__Kb * DAG_Ca_PLA2_p_541_0_ @@ -3475,26 +3922,26 @@ - kinetics_479_0_ - DAG_Ca_PLA2_act_588_0__Kf - DAG_632_0_ - PLA2_Ca_p_553_0_ + kinetics_451_0_ + DAG_Ca_PLA2_act_561_0__Kf + DAG_605_0_ + PLA2_Ca_p_526_0_ - kinetics_479_0_ - DAG_Ca_PLA2_act_588_0__Kb - DAG_Ca_PLA2_p_568_0_ + kinetics_451_0_ + DAG_Ca_PLA2_act_561_0__Kb + DAG_Ca_PLA2_p_541_0_ - - + + - + I need to check if the AA degradation pathway really leads back to APC. Anyway, it is a convenient buffered pool to dump it back into. For the purposes of the full model we use a rate of degradation of 0.2/sec Raised decay to 0.4 : see PLA35.g notes for Feb17 @@ -3503,37 +3950,37 @@ 213.235294118 - -19.2771084337 + 19.2771084337 white 1 - + - + - kinetics_479_0_ * Degrade_AA_590_0__Kf * Arachidonic_Acid_596_0_ + kinetics_451_0_ * Degrade_AA_563_0__Kf * Arachidonic_Acid_569_0_ - kinetics_479_0_ - Degrade_AA_590_0__Kf - Arachidonic_Acid_596_0_ + kinetics_451_0_ + Degrade_AA_563_0__Kf + Arachidonic_Acid_569_0_ - + - + To start off, same kinetics as the PLA2-Ca-act direct pathway. Oops ! Missed out the Ca input to this pathway first time round. Let's raise the forward rate about 3x to 5e-6. This will let us reduce the rather high rates we have used for the kenz on PLA2*-Ca. In fact, it may be that the rates are not that different, just that this pathway for getting the PLA2 to the memb is more efficien.... @@ -3542,22 +3989,22 @@ 227.941176471 - -19.2771084337 + 19.2771084337 white 1 - - + + - + - kinetics_479_0_ * PLA2_p_Ca_act_592_0__Kf * PLA2_p_580_0_*Ca_1197_0_-kinetics_479_0_ * PLA2_p_Ca_act_592_0__Kb * PLA2_p_Ca_575_0_ + kinetics_451_0_ * PLA2_p_Ca_act_565_0__Kf * PLA2_p_553_0_*Ca_1170_0_-kinetics_451_0_ * PLA2_p_Ca_act_565_0__Kb * PLA2_p_Ca_548_0_ @@ -3565,60 +4012,60 @@ - kinetics_479_0_ - PLA2_p_Ca_act_592_0__Kf - PLA2_p_580_0_ - Ca_1197_0_ + kinetics_451_0_ + PLA2_p_Ca_act_565_0__Kf + PLA2_p_553_0_ + Ca_1170_0_ - kinetics_479_0_ - PLA2_p_Ca_act_592_0__Kb - PLA2_p_Ca_575_0_ + kinetics_451_0_ + PLA2_p_Ca_act_565_0__Kb + PLA2_p_Ca_548_0_ - - + + - + 242.647058824 - -19.2771084337 + 19.2771084337 white 1 - + - + - kinetics_479_0_ * dephosphorylate_PLA2_p_594_0__Kf * PLA2_p_580_0_ + kinetics_451_0_ * dephosphorylate_PLA2_p_567_0__Kf * PLA2_p_553_0_ - kinetics_479_0_ - dephosphorylate_PLA2_p_594_0__Kf - PLA2_p_580_0_ + kinetics_451_0_ + dephosphorylate_PLA2_p_567_0__Kf + PLA2_p_553_0_ - + - + Affinity for Ca = 1uM without AlF, 0.1 with: from Smrcka et al science 251 pp 804-807 1991 so [Ca].kf = kb so kb/kf = 1 * 6e5 = 1/1.66e-6 11 June 1996: Raised affinity to 5e-6 to maintain balance. See notes. @@ -3627,22 +4074,22 @@ 301.470588235 - -19.2771084337 + 19.2771084337 white 2 - - + + - + - kinetics_479_0_ * Act_PLC_Ca_616_0__Kf * PLC_600_0_*Ca_1197_0_-kinetics_479_0_ * Act_PLC_Ca_616_0__Kb * PLC_Ca_604_0_ + kinetics_451_0_ * Act_PLC_Ca_589_0__Kf * Ca_1170_0_*PLC_573_0_-kinetics_451_0_ * Act_PLC_Ca_589_0__Kb * PLC_Ca_577_0_ @@ -3650,26 +4097,26 @@ - kinetics_479_0_ - Act_PLC_Ca_616_0__Kf - PLC_600_0_ - Ca_1197_0_ + kinetics_451_0_ + Act_PLC_Ca_589_0__Kf + Ca_1170_0_ + PLC_573_0_ - kinetics_479_0_ - Act_PLC_Ca_616_0__Kb - PLC_Ca_604_0_ + kinetics_451_0_ + Act_PLC_Ca_589_0__Kb + PLC_Ca_577_0_ - - + + - + The enzyme is IP3 5-phosphomonesterase. about 45K. Actual products are Ins(1,4)P2, and cIns(1:2,4,5)P3. review in Majerus et al Science 234 1519-1526, 1986. Meyer and Stryer 1988 PNAS 85:5051-5055 est decay of IP3 at 1-3/sec @@ -3678,37 +4125,37 @@ 316.176470588 - -19.2771084337 + 19.2771084337 white 2 - + - + - kinetics_479_0_ * Degrade_IP3_618_0__Kf * IP3_634_0_ + kinetics_451_0_ * Degrade_IP3_591_0__Kf * IP3_607_0_ - kinetics_479_0_ - Degrade_IP3_618_0__Kf - IP3_634_0_ + kinetics_451_0_ + Degrade_IP3_591_0__Kf + IP3_607_0_ - + - + These rates are the same as for degrading IP3, but I am sure that they could be improved. Lets double kf to 0.2, since the amount of DAG in the cell should be _lessthan_= 1uM. Need to double it again, for the same reason. kf now 0.5 27 June 1996 kf is now 0.02 to get 50 sec time course 30 Aug 1997: Raised kf to 0.11 to accomodate PLC_gamma 27 Mar 1998: kf now 0.15 for PLC_gamma @@ -3717,37 +4164,37 @@ 330.882352941 - -19.2771084337 + 19.2771084337 white 2 - + - + - kinetics_479_0_ * Degrade_DAG_620_0__Kf * DAG_632_0_ + kinetics_451_0_ * Degrade_DAG_593_0__Kf * DAG_605_0_ - kinetics_479_0_ - Degrade_DAG_620_0__Kf - DAG_632_0_ + kinetics_451_0_ + Degrade_DAG_593_0__Kf + DAG_605_0_ - + - + Affinity for Gq is _greaterthan_ 20 nM (Smrcka et al Science251 804-807 1991) so [Gq].kf = kb so 40nM * 6e5 = kb/kf = 24e3 so kf = 4.2e-5, kb =1 @@ -3756,22 +4203,22 @@ 345.588235294 - -19.2771084337 + 19.2771084337 white 2 - - + + - + - kinetics_479_0_ * Act_PLC_by_Gq_622_0__Kf * G_pGTP_1113_0_*PLC_Ca_604_0_-kinetics_479_0_ * Act_PLC_by_Gq_622_0__Kb * PLC_Ca_Gq_609_0_ + kinetics_451_0_ * Act_PLC_by_Gq_595_0__Kf * PLC_Ca_577_0_*G_pGTP_1086_0_-kinetics_451_0_ * Act_PLC_by_Gq_595_0__Kb * PLC_Ca_Gq_582_0_ @@ -3779,26 +4226,26 @@ - kinetics_479_0_ - Act_PLC_by_Gq_622_0__Kf - G_pGTP_1113_0_ - PLC_Ca_604_0_ + kinetics_451_0_ + Act_PLC_by_Gq_595_0__Kf + PLC_Ca_577_0_ + G_pGTP_1086_0_ - kinetics_479_0_ - Act_PLC_by_Gq_622_0__Kb - PLC_Ca_Gq_609_0_ + kinetics_451_0_ + Act_PLC_by_Gq_595_0__Kb + PLC_Ca_Gq_582_0_ - - + + - + This process is assumed to be directly caused by the inactivation of the G*GTP to G*GDP. Hence, kf = .013 /sec = 0.8/min, same as the rate for Inact-G. kb = 0 since this is irreversible. We may be interested in studying the role of PLC as a GAP. If so, the kf would be faster here than in Inact-G @@ -3807,38 +4254,38 @@ 360.294117647 - -19.2771084337 + 19.2771084337 white 2 - + - - + + - kinetics_479_0_ * Inact_PLC_Gq_624_0__Kf * PLC_Ca_Gq_609_0_ + kinetics_451_0_ * Inact_PLC_Gq_597_0__Kf * PLC_Ca_Gq_582_0_ - kinetics_479_0_ - Inact_PLC_Gq_624_0__Kf - PLC_Ca_Gq_609_0_ + kinetics_451_0_ + Inact_PLC_Gq_597_0__Kf + PLC_Ca_Gq_582_0_ - + - + this binding does not produce active PLC. This step was needed to implement the described (Smrcka et al) increase in affinity for Ca by PLC once Gq was bound. The kinetics are the same as the binding step for Ca-PLC to Gq. June 1996: Changed the kf to 4.2e-5 to 4.2e-6 to preserve balance around the reactions. @@ -3847,22 +4294,22 @@ 375.0 - -19.2771084337 + 19.2771084337 white 2 - - + + - + - kinetics_479_0_ * PLC_bind_Gq_626_0__Kf * PLC_600_0_*G_pGTP_1113_0_-kinetics_479_0_ * PLC_bind_Gq_626_0__Kb * PLC_Gq_614_0_ + kinetics_451_0_ * PLC_bind_Gq_599_0__Kf * PLC_573_0_*G_pGTP_1086_0_-kinetics_451_0_ * PLC_bind_Gq_599_0__Kb * PLC_Gq_587_0_ @@ -3870,26 +4317,26 @@ - kinetics_479_0_ - PLC_bind_Gq_626_0__Kf - PLC_600_0_ - G_pGTP_1113_0_ + kinetics_451_0_ + PLC_bind_Gq_599_0__Kf + PLC_573_0_ + G_pGTP_1086_0_ - kinetics_479_0_ - PLC_bind_Gq_626_0__Kb - PLC_Gq_614_0_ + kinetics_451_0_ + PLC_bind_Gq_599_0__Kb + PLC_Gq_587_0_ - - + + - + this step has a high affinity for Ca, from Smrcka et al. 0.1uM so kf /kb = 1/6e4 = 1.666e-5:1. See the Act-PLC-by-Gq reac. 11 Jun 1996: Raised kf to 5e-5 based on match to conc-eff curves from Smrcka et al. @@ -3898,22 +4345,22 @@ 389.705882353 - -19.2771084337 + 19.2771084337 white 2 - - + + - + - kinetics_479_0_ * PLC_Gq_bind_Ca_628_0__Kf * Ca_1197_0_*PLC_Gq_614_0_-kinetics_479_0_ * PLC_Gq_bind_Ca_628_0__Kb * PLC_Ca_Gq_609_0_ + kinetics_451_0_ * PLC_Gq_bind_Ca_601_0__Kf * Ca_1170_0_*PLC_Gq_587_0_-kinetics_451_0_ * PLC_Gq_bind_Ca_601_0__Kb * PLC_Ca_Gq_582_0_ @@ -3921,26 +4368,26 @@ - kinetics_479_0_ - PLC_Gq_bind_Ca_628_0__Kf - Ca_1197_0_ - PLC_Gq_614_0_ + kinetics_451_0_ + PLC_Gq_bind_Ca_601_0__Kf + Ca_1170_0_ + PLC_Gq_587_0_ - kinetics_479_0_ - PLC_Gq_bind_Ca_628_0__Kb - PLC_Ca_Gq_609_0_ + kinetics_451_0_ + PLC_Gq_bind_Ca_601_0__Kb + PLC_Ca_Gq_582_0_ - - + + - + The rate consts give a total binding affinity of only @@ -3949,22 +4396,22 @@ 448.529411765 - -19.2771084337 + 19.2771084337 white 3 - - + + - + - kinetics_479_0_ * Antag_bind_Rec_Gq_644_0__Kf * mGluRAntag_640_0_*Rec_Gq_1095_0_-kinetics_479_0_ * Antag_bind_Rec_Gq_644_0__Kb * Blocked_Rec_Gq_642_0_ + kinetics_451_0_ * Antag_bind_Rec_Gq_617_0__Kf * Rec_Gq_1068_0_*mGluRAntag_613_0_-kinetics_451_0_ * Antag_bind_Rec_Gq_617_0__Kb * Blocked_Rec_Gq_615_0_ @@ -3972,45 +4419,45 @@ - kinetics_479_0_ - Antag_bind_Rec_Gq_644_0__Kf - mGluRAntag_640_0_ - Rec_Gq_1095_0_ + kinetics_451_0_ + Antag_bind_Rec_Gq_617_0__Kf + Rec_Gq_1068_0_ + mGluRAntag_613_0_ - kinetics_479_0_ - Antag_bind_Rec_Gq_644_0__Kb - Blocked_Rec_Gq_642_0_ + kinetics_451_0_ + Antag_bind_Rec_Gq_617_0__Kb + Blocked_Rec_Gq_615_0_ - - + + - + 595.588235294 - -19.2771084337 + 19.2771084337 white 4 - - + + - + - kinetics_479_0_ * mGluR_barr2_Raf_scaffolding_706_0__Kf * Internal_mGluR_p_dot_barr2_1547_0_*craf_1_668_0_-kinetics_479_0_ * mGluR_barr2_Raf_scaffolding_706_0__Kb * craf_1_p_670_0_ + kinetics_451_0_ * mGluR_barr2_Raf_scaffolding_679_0__Kf * Internal_mGluR_p_dot_barr2_1520_0_*craf_1_641_0_-kinetics_451_0_ * mGluR_barr2_Raf_scaffolding_679_0__Kb * craf_1_p_643_0_ @@ -4018,26 +4465,26 @@ - kinetics_479_0_ - mGluR_barr2_Raf_scaffolding_706_0__Kf - Internal_mGluR_p_dot_barr2_1547_0_ - craf_1_668_0_ + kinetics_451_0_ + mGluR_barr2_Raf_scaffolding_679_0__Kf + Internal_mGluR_p_dot_barr2_1520_0_ + craf_1_641_0_ - kinetics_479_0_ - mGluR_barr2_Raf_scaffolding_706_0__Kb - craf_1_p_670_0_ + kinetics_451_0_ + mGluR_barr2_Raf_scaffolding_679_0__Kb + craf_1_p_643_0_ - - + + - + Assume the binding is fast and limited only by the amount of Ras* available. So kf=kb/[craf-1] If kb is 1/sec, then kf = 1/0.2 uM = 1/(0.2 * 6e5) = 8.3e-6 Later: Raise it by 10 X to 4e-5 From Hallberg et al JBC 269:6 3913-3916 1994, 3% of cellular Raf is complexed with Ras. So we raise kb 4x to 4 This step needed to memb-anchor and activate Raf: Leevers et al Nature 369 411-414 (I don't.... @@ -4046,22 +4493,22 @@ 742.647058824 - -19.2771084337 + 19.2771084337 white 5 - - + + - + - kinetics_479_0_ * Ras_act_craf_743_0__Kf * GTP_Ras_725_0_*craf_1_p_670_0_-kinetics_479_0_ * Ras_act_craf_743_0__Kb * Raf_p_GTP_Ras_696_0_ + kinetics_451_0_ * Ras_act_craf_716_0__Kf * GTP_Ras_698_0_*craf_1_p_643_0_-kinetics_451_0_ * Ras_act_craf_716_0__Kb * Raf_p_GTP_Ras_669_0_ @@ -4069,26 +4516,26 @@ - kinetics_479_0_ - Ras_act_craf_743_0__Kf - GTP_Ras_725_0_ - craf_1_p_670_0_ + kinetics_451_0_ + Ras_act_craf_716_0__Kf + GTP_Ras_698_0_ + craf_1_p_643_0_ - kinetics_479_0_ - Ras_act_craf_743_0__Kb - Raf_p_GTP_Ras_696_0_ + kinetics_451_0_ + Ras_act_craf_716_0__Kb + Raf_p_GTP_Ras_669_0_ - - + + - + SoS/GEF is present at 50 nM ie 3e4/cell. BetaGamma maxes out at 9e4. Assume we have 1/3 of the GEF active when the BetaGamma is 1.5e4. so 1e4 * kb = 2e4 * 1.5e4 * kf, so kf/kb = 3e-5. The rate of this equil should be reasonably fast, say 1/sec @@ -4097,22 +4544,22 @@ 757.352941176 - -19.2771084337 + 19.2771084337 white 5 - - + + - + - kinetics_479_0_ * bg_act_GEF_745_0__Kf * inact_GEF_715_0_*BetaGamma_1111_0_-kinetics_479_0_ * bg_act_GEF_745_0__Kb * GEF_Gprot_bg_710_0_ + kinetics_451_0_ * bg_act_GEF_718_0__Kf * inact_GEF_688_0_*BetaGamma_1084_0_-kinetics_451_0_ * bg_act_GEF_718_0__Kb * GEF_Gprot_bg_683_0_ @@ -4120,60 +4567,60 @@ - kinetics_479_0_ - bg_act_GEF_745_0__Kf - inact_GEF_715_0_ - BetaGamma_1111_0_ + kinetics_451_0_ + bg_act_GEF_718_0__Kf + inact_GEF_688_0_ + BetaGamma_1084_0_ - kinetics_479_0_ - bg_act_GEF_745_0__Kb - GEF_Gprot_bg_710_0_ + kinetics_451_0_ + bg_act_GEF_718_0__Kb + GEF_Gprot_bg_683_0_ - - + + - + 772.058823529 - -19.2771084337 + 19.2771084337 white 5 - + - + - kinetics_479_0_ * dephosph_GEF_747_0__Kf * GEF_p_720_0_ + kinetics_451_0_ * dephosph_GEF_720_0__Kf * GEF_p_693_0_ - kinetics_479_0_ - dephosph_GEF_747_0__Kf - GEF_p_720_0_ + kinetics_451_0_ + dephosph_GEF_720_0__Kf + GEF_p_693_0_ - + - + This is extremely slow (1e-4), but it is significant as so little GAP actually gets complexed with it that the total GTP turnover rises only by 2-3 X (see Gibbs et al, JBC 265(33) 20437-20422) and Eccleston et al JBC 268(36) 27012-27019 kf = 1e-4 @@ -4182,37 +4629,37 @@ 786.764705882 - -19.2771084337 + 19.2771084337 white 5 - + - + - kinetics_479_0_ * Ras_intrinsic_GTPase_749_0__Kf * GTP_Ras_725_0_ + kinetics_451_0_ * Ras_intrinsic_GTPase_722_0__Kf * GTP_Ras_698_0_ - kinetics_479_0_ - Ras_intrinsic_GTPase_749_0__Kf - GTP_Ras_725_0_ + kinetics_451_0_ + Ras_intrinsic_GTPase_722_0__Kf + GTP_Ras_698_0_ - + - + Assume a reasonably good rate for dephosphorylating it, 1/sec @@ -4221,37 +4668,37 @@ 801.470588235 - -19.2771084337 + 19.2771084337 white 5 - + - + - kinetics_479_0_ * dephosph_GAP_751_0__Kf * GAP_p_729_0_ + kinetics_451_0_ * dephosph_GAP_724_0__Kf * GAP_p_702_0_ - kinetics_479_0_ - dephosph_GAP_751_0__Kf - GAP_p_729_0_ + kinetics_451_0_ + dephosph_GAP_724_0__Kf + GAP_p_702_0_ - + - + We have no numbers for this. It is probably between the two extremes represented by the CaMKII phosph states, and I have used guesses based on this. kf=1e-4 kb=1 The reaction is based on Farnsworth et al Nature 376 524-527 1995 @@ -4260,22 +4707,22 @@ 816.176470588 - -19.2771084337 + 19.2771084337 white 5 - - + + - + - kinetics_479_0_ * CaM_bind_GEF_753_0__Kf * inact_GEF_715_0_*CaM_Ca4_877_0_-kinetics_479_0_ * CaM_bind_GEF_753_0__Kb * CaM_GEF_738_0_ + kinetics_451_0_ * CaM_bind_GEF_726_0__Kf * inact_GEF_688_0_*CaM_Ca4_850_0_-kinetics_451_0_ * CaM_bind_GEF_726_0__Kb * CaM_GEF_711_0_ @@ -4283,60 +4730,60 @@ - kinetics_479_0_ - CaM_bind_GEF_753_0__Kf - inact_GEF_715_0_ - CaM_Ca4_877_0_ + kinetics_451_0_ + CaM_bind_GEF_726_0__Kf + inact_GEF_688_0_ + CaM_Ca4_850_0_ - kinetics_479_0_ - CaM_bind_GEF_753_0__Kb - CaM_GEF_738_0_ + kinetics_451_0_ + CaM_bind_GEF_726_0__Kb + CaM_GEF_711_0_ - - + + - + 830.882352941 - -19.2771084337 + 19.2771084337 white 5 - + - + - kinetics_479_0_ * dephosph_inact_GEF_p_755_0__Kf * inact_GEF_p_736_0_ + kinetics_451_0_ * dephosph_inact_GEF_p_728_0__Kf * inact_GEF_p_709_0_ - kinetics_479_0_ - dephosph_inact_GEF_p_755_0__Kf - inact_GEF_p_736_0_ + kinetics_451_0_ + dephosph_inact_GEF_p_728_0__Kf + inact_GEF_p_709_0_ - + - + Affinity of EGFR for EGF is complex: depends on [EGFR]. We'll assume fixed [EGFR] and use exptal affinity ~20 nM (see Sherrill and Kyte Biochem 1996 35 5705-5718, Berkers et al JBC 266:2 922-927 1991, Sorokin et al JBC 269:13 9752-9759 1994). Tau =~2 min (Davis et al JBC 263:11 5373-5379 1988) or Berkers Kass = 6.2e5/M/sec, Kdiss=3.5e-4/sec. Sherrill and Kyte have Hill Coeff=1.7 @@ -4345,22 +4792,22 @@ 889.705882353 - -19.2771084337 + 19.2771084337 white 6 - - + + - + - kinetics_479_0_ * act_EGFR_773_0__Kf * EGF_769_0_*EGFR_759_0_-kinetics_479_0_ * act_EGFR_773_0__Kb * L_dot_EGFR_761_0_ + kinetics_451_0_ * act_EGFR_746_0__Kf * EGFR_732_0_*EGF_742_0_-kinetics_451_0_ * act_EGFR_746_0__Kb * L_dot_EGFR_734_0_ @@ -4368,26 +4815,26 @@ - kinetics_479_0_ - act_EGFR_773_0__Kf - EGF_769_0_ - EGFR_759_0_ + kinetics_451_0_ + act_EGFR_746_0__Kf + EGFR_732_0_ + EGF_742_0_ - kinetics_479_0_ - act_EGFR_773_0__Kb - L_dot_EGFR_761_0_ + kinetics_451_0_ + act_EGFR_746_0__Kb + L_dot_EGFR_734_0_ - - + + - + See Helin and Beguinot JBC 266:13 1991 pg 8363-8368. In Fig 3 they have internalization tau about 10 min, equil at about 20% EGF available. So kf = 4x kb, and 1/(kf + kb) = 600 sec so kb = 1/3K = 3.3e-4, and kf = 1.33e-3. This doesn't take into account the unbound receptor, so we need to push the kf up a bit, to 0.002 @@ -4396,21 +4843,21 @@ 904.411764706 - -19.2771084337 + 19.2771084337 white 6 - + - + - kinetics_479_0_ * Internalize_775_0__Kf * L_dot_EGFR_761_0_-kinetics_479_0_ * Internalize_775_0__Kb * Internal_L_dot_EGFR_771_0_ + kinetics_451_0_ * Internalize_748_0__Kf * L_dot_EGFR_734_0_-kinetics_451_0_ * Internalize_748_0__Kb * Internal_L_dot_EGFR_744_0_ @@ -4418,25 +4865,25 @@ - kinetics_479_0_ - Internalize_775_0__Kf - L_dot_EGFR_761_0_ + kinetics_451_0_ + Internalize_748_0__Kf + L_dot_EGFR_734_0_ - kinetics_479_0_ - Internalize_775_0__Kb - Internal_L_dot_EGFR_771_0_ + kinetics_451_0_ + Internalize_748_0__Kb + Internal_L_dot_EGFR_744_0_ - - + + - + Time course of decline of phosph is 20 min. Part of this is the turnoff time of the EGFR itself. Lets assume a tau of 10 min for this dephosph. It may be wildly off. @@ -4445,37 +4892,37 @@ 7.35294117647 - -212.048192771 + 212.048192771 white 7 - + - + - kinetics_479_0_ * SHC_p_dephospho_800_0__Kf * SHC_p_786_0_ + kinetics_451_0_ * SHC_p_dephospho_773_0__Kf * SHC_p_759_0_ - kinetics_479_0_ - SHC_p_dephospho_800_0__Kf - SHC_p_786_0_ + kinetics_451_0_ + SHC_p_dephospho_773_0__Kf + SHC_p_759_0_ - + - + Sasaoka et al JBC 269:51 pp 32621 1994, table on pg 32623 indicates that this pathway accounts for about 50% of the GEF activation. (88% - 39%). Error is large, about 20%. Fig 1 is most useful in constraining rates. Chook et al JBC 271:48 pp 30472, 1996 say that the Kd is 0.2 uM for Shc binding to EGFR. The Kd for Grb direct binding is 0.7, so we'll ignore it. @@ -4484,22 +4931,22 @@ 22.0588235294 - -212.048192771 + 212.048192771 white 7 - - + + - + - kinetics_479_0_ * SHC_bind_Sos_dot_Grb2_802_0__Kf * Sos_dot_Grb2_792_0_*SHC_p_786_0_-kinetics_479_0_ * SHC_bind_Sos_dot_Grb2_802_0__Kb * SHC_p_dot_Sos_dot_Grb2_779_0_ + kinetics_451_0_ * SHC_bind_Sos_dot_Grb2_775_0__Kf * Sos_dot_Grb2_765_0_*SHC_p_759_0_-kinetics_451_0_ * SHC_bind_Sos_dot_Grb2_775_0__Kb * SHC_p_dot_Sos_dot_Grb2_752_0_ @@ -4507,26 +4954,26 @@ - kinetics_479_0_ - SHC_bind_Sos_dot_Grb2_802_0__Kf - Sos_dot_Grb2_792_0_ - SHC_p_786_0_ + kinetics_451_0_ + SHC_bind_Sos_dot_Grb2_775_0__Kf + Sos_dot_Grb2_765_0_ + SHC_p_759_0_ - kinetics_479_0_ - SHC_bind_Sos_dot_Grb2_802_0__Kb - SHC_p_dot_Sos_dot_Grb2_779_0_ + kinetics_451_0_ + SHC_bind_Sos_dot_Grb2_775_0__Kb + SHC_p_dot_Sos_dot_Grb2_752_0_ - - + + - + Same rates as Grb2_bind_Sos: Porfiri and McCormick JBC 271:10 pp 5871 1996 show that the binding is not affected by the phosph. @@ -4535,22 +4982,22 @@ 36.7647058824 - -212.048192771 + 212.048192771 white 7 - - + + - + - kinetics_479_0_ * Grb2_bind_Sos_p_804_0__Kf * Sos_p_794_0_*Grb2_790_0_-kinetics_479_0_ * Grb2_bind_Sos_p_804_0__Kb * Sos_p_dot_Grb2_788_0_ + kinetics_451_0_ * Grb2_bind_Sos_p_777_0__Kf * Grb2_763_0_*Sos_p_767_0_-kinetics_451_0_ * Grb2_bind_Sos_p_777_0__Kb * Sos_p_dot_Grb2_761_0_ @@ -4558,26 +5005,26 @@ - kinetics_479_0_ - Grb2_bind_Sos_p_804_0__Kf - Sos_p_794_0_ - Grb2_790_0_ + kinetics_451_0_ + Grb2_bind_Sos_p_777_0__Kf + Grb2_763_0_ + Sos_p_767_0_ - kinetics_479_0_ - Grb2_bind_Sos_p_804_0__Kb - Sos_p_dot_Grb2_788_0_ + kinetics_451_0_ + Grb2_bind_Sos_p_777_0__Kb + Sos_p_dot_Grb2_761_0_ - - + + - + The only clue I have to these rates is from the time courses of the EGF activation, which is around 1 to 5 min. The dephosph would be expected to be of the same order, perhaps a bit longer. Lets use 0.002 which is about 8 min. Sep 17: The transient activation curve matches better with kf = 0.001 @@ -4586,37 +5033,37 @@ 51.4705882353 - -212.048192771 + 212.048192771 white 7 - + - + - kinetics_479_0_ * dephosph_Sos_806_0__Kf * Sos_p_794_0_ + kinetics_451_0_ * dephosph_Sos_779_0__Kf * Sos_p_767_0_ - kinetics_479_0_ - dephosph_Sos_806_0__Kf - Sos_p_794_0_ + kinetics_451_0_ + dephosph_Sos_779_0__Kf + Sos_p_767_0_ - + - + As there are 2 SH3 domains, this reaction could be 2nd order. I have a Kd of 22 uM from peptide binding (Lemmon et al JBC 269:50 pg 31653). However, Chook et al JBC 271:48 pg30472 say it is 0.4uM with purified proteins, so we believe them. They say it is 1:1 binding. @@ -4625,22 +5072,22 @@ 66.1764705882 - -212.048192771 + 212.048192771 white 7 - - + + - + - kinetics_479_0_ * Grb2_bind_Sos_808_0__Kf * Sos_796_0_*Grb2_790_0_-kinetics_479_0_ * Grb2_bind_Sos_808_0__Kb * Sos_dot_Grb2_792_0_ + kinetics_451_0_ * Grb2_bind_Sos_781_0__Kf * Sos_769_0_*Grb2_763_0_-kinetics_451_0_ * Grb2_bind_Sos_781_0__Kb * Sos_dot_Grb2_765_0_ @@ -4648,45 +5095,45 @@ - kinetics_479_0_ - Grb2_bind_Sos_808_0__Kf - Sos_796_0_ - Grb2_790_0_ + kinetics_451_0_ + Grb2_bind_Sos_781_0__Kf + Sos_769_0_ + Grb2_763_0_ - kinetics_479_0_ - Grb2_bind_Sos_808_0__Kb - Sos_dot_Grb2_792_0_ + kinetics_451_0_ + Grb2_bind_Sos_781_0__Kb + Sos_dot_Grb2_765_0_ - - + + - + 80.8823529412 - -212.048192771 + 212.048192771 white 7 - - + + - + - kinetics_479_0_ * Grb2_bind_SHC_810_0__Kf * SHC_p_786_0_*Grb2_790_0_-kinetics_479_0_ * Grb2_bind_SHC_810_0__Kb * SHC_p_Grb2_clx_798_0_ + kinetics_451_0_ * Grb2_bind_SHC_783_0__Kf * Grb2_763_0_*SHC_p_759_0_-kinetics_451_0_ * Grb2_bind_SHC_783_0__Kb * SHC_p_Grb2_clx_771_0_ @@ -4694,26 +5141,26 @@ - kinetics_479_0_ - Grb2_bind_SHC_810_0__Kf - SHC_p_786_0_ - Grb2_790_0_ + kinetics_451_0_ + Grb2_bind_SHC_783_0__Kf + Grb2_763_0_ + SHC_p_759_0_ - kinetics_479_0_ - Grb2_bind_SHC_810_0__Kb - SHC_p_Grb2_clx_798_0_ + kinetics_451_0_ + Grb2_bind_SHC_783_0__Kb + SHC_p_Grb2_clx_771_0_ - - + + - + Nice curves from Homma et al JBC 263:14 6592-6598 1988 Fig 5c. The activity falls above 10 uM, but that is too high to reach physiologically anyway, so we'll ignore the higher pts and match the lower ones only. Half-max at 1 uM. But Wahl et al JBC 267:15 10447-10456 1992 have half-max at 56 nM which is what I'll use. @@ -4722,22 +5169,22 @@ 154.411764706 - -212.048192771 + 212.048192771 white 8 - - + + - + - kinetics_479_0_ * Ca_act_PLC_g_831_0__Kf * Ca_1197_0_*PLC_g_814_0_-kinetics_479_0_ * Ca_act_PLC_g_831_0__Kb * Ca_dot_PLC_g_818_0_ + kinetics_451_0_ * Ca_act_PLC_g_804_0__Kf * Ca_1170_0_*PLC_g_787_0_-kinetics_451_0_ * Ca_act_PLC_g_804_0__Kb * Ca_dot_PLC_g_791_0_ @@ -4745,26 +5192,26 @@ - kinetics_479_0_ - Ca_act_PLC_g_831_0__Kf - Ca_1197_0_ - PLC_g_814_0_ + kinetics_451_0_ + Ca_act_PLC_g_804_0__Kf + Ca_1170_0_ + PLC_g_787_0_ - kinetics_479_0_ - Ca_act_PLC_g_831_0__Kb - Ca_dot_PLC_g_818_0_ + kinetics_451_0_ + Ca_act_PLC_g_804_0__Kb + Ca_dot_PLC_g_791_0_ - - + + - + Again, we refer to Homma et al and Wahl et al, for preference using Wahl. Half-Max of the phosph form is at 316 nM. Use kb of 10 as this is likely to be pretty fast. Did some curve comparisons, and instead of 316 nM giving a kf of 5.27e-5, we will use 8e-5 for kf. 16 Sep 97. As we are now phosphorylating the Ca-bound form, equils have shifted. kf should now be 2e-5 to match the curves. @@ -4773,22 +5220,22 @@ 169.117647059 - -212.048192771 + 212.048192771 white 8 - - + + - + - kinetics_479_0_ * Ca_act_PLC_g_p_833_0__Kf * PLC_g_p_816_0_*Ca_1197_0_-kinetics_479_0_ * Ca_act_PLC_g_p_833_0__Kb * Ca_dot_PLC_g_p_822_0_ + kinetics_451_0_ * Ca_act_PLC_g_p_806_0__Kf * Ca_1170_0_*PLC_g_p_789_0_-kinetics_451_0_ * Ca_act_PLC_g_p_806_0__Kb * Ca_dot_PLC_g_p_795_0_ @@ -4796,94 +5243,94 @@ - kinetics_479_0_ - Ca_act_PLC_g_p_833_0__Kf - PLC_g_p_816_0_ - Ca_1197_0_ + kinetics_451_0_ + Ca_act_PLC_g_p_806_0__Kf + Ca_1170_0_ + PLC_g_p_789_0_ - kinetics_479_0_ - Ca_act_PLC_g_p_833_0__Kb - Ca_dot_PLC_g_p_822_0_ + kinetics_451_0_ + Ca_act_PLC_g_p_806_0__Kb + Ca_dot_PLC_g_p_795_0_ - - + + - + 183.823529412 - -212.048192771 + 212.048192771 white 8 - + - + - kinetics_479_0_ * dephosph_PLC_g_835_0__Kf * Ca_dot_PLC_g_p_822_0_ + kinetics_451_0_ * dephosph_PLC_g_808_0__Kf * Ca_dot_PLC_g_p_795_0_ - kinetics_479_0_ - dephosph_PLC_g_835_0__Kf - Ca_dot_PLC_g_p_822_0_ + kinetics_451_0_ + dephosph_PLC_g_808_0__Kf + Ca_dot_PLC_g_p_795_0_ - + - + 198.529411765 - -212.048192771 + 212.048192771 white 8 - + - + - kinetics_479_0_ * PLC_g_p_dephospho_837_0__Kf * PLC_g_p_816_0_ + kinetics_451_0_ * PLC_g_p_dephospho_810_0__Kf * PLC_g_p_789_0_ - kinetics_479_0_ - PLC_g_p_dephospho_837_0__Kf - PLC_g_p_816_0_ + kinetics_451_0_ + PLC_g_p_dephospho_810_0__Kf + PLC_g_p_789_0_ - + - + This is tricky. There is some cooperativity here arising from interactions between the subunits of the CAMKII holoenzyme. However, the stoichiometry is 1. Kb/Kf = 6e4 #/cell. Rate is fast (see Hanson et al Neuron 12 943-956 1994) so lets say kb = 10. This gives kf = 1.6667e-4 H_andS AnnRev Biochem 92 give tau for dissoc as 0.2 sec at low Ca, 0.4 at high. Low Ca = 100 nM = physiol. @@ -4892,22 +5339,22 @@ 301.470588235 - -212.048192771 + 212.048192771 white 9 - - + + - + - kinetics_479_0_ * CaMKII_bind_CaM_869_0__Kf * CaMKII_841_0_*CaM_Ca4_877_0_-kinetics_479_0_ * CaMKII_bind_CaM_869_0__Kb * CaMKII_CaM_843_0_ + kinetics_451_0_ * CaMKII_bind_CaM_842_0__Kf * CaM_Ca4_850_0_*CaMKII_814_0_-kinetics_451_0_ * CaMKII_bind_CaM_842_0__Kb * CaMKII_CaM_816_0_ @@ -4915,26 +5362,26 @@ - kinetics_479_0_ - CaMKII_bind_CaM_869_0__Kf - CaMKII_841_0_ - CaM_Ca4_877_0_ + kinetics_451_0_ + CaMKII_bind_CaM_842_0__Kf + CaM_Ca4_850_0_ + CaMKII_814_0_ - kinetics_479_0_ - CaMKII_bind_CaM_869_0__Kb - CaMKII_CaM_843_0_ + kinetics_451_0_ + CaMKII_bind_CaM_842_0__Kb + CaMKII_CaM_816_0_ - - + + - + Affinity is up 1000X. Time to release is about 20 sec, so the kb is OK at 0.1 This makes Kf around 1.6666e-3 @@ -4943,22 +5390,22 @@ 316.176470588 - -212.048192771 + 212.048192771 white 9 - - + + - + - kinetics_479_0_ * CaMKII_thr286_bind_CaM_871_0__Kf * CaMKII_thr286_849_0_*CaM_Ca4_877_0_-kinetics_479_0_ * CaMKII_thr286_bind_CaM_871_0__Kb * CaMKII_thr286_p_CaM_845_0_ + kinetics_451_0_ * CaMKII_thr286_bind_CaM_844_0__Kf * CaM_Ca4_850_0_*CaMKII_thr286_822_0_-kinetics_451_0_ * CaMKII_thr286_bind_CaM_844_0__Kb * CaMKII_thr286_p_CaM_818_0_ @@ -4966,26 +5413,26 @@ - kinetics_479_0_ - CaMKII_thr286_bind_CaM_871_0__Kf - CaMKII_thr286_849_0_ - CaM_Ca4_877_0_ + kinetics_451_0_ + CaMKII_thr286_bind_CaM_844_0__Kf + CaM_Ca4_850_0_ + CaMKII_thr286_822_0_ - kinetics_479_0_ - CaMKII_thr286_bind_CaM_871_0__Kb - CaMKII_thr286_p_CaM_845_0_ + kinetics_451_0_ + CaMKII_thr286_bind_CaM_844_0__Kb + CaMKII_thr286_p_CaM_818_0_ - - + + - + This reaction represents one of the big unknowns in CaMK-II biochemistry: what maintains the basal level of phosphorylation on thr 286 ? See Hanson and Schulman Ann Rev Biochem 1992 61:559-601, specially pg 580, for review. I have not been able to find any compelling mechanism in the literature, but fortunately the level of basal activity is well documented. @@ -4994,37 +5441,37 @@ 330.882352941 - -212.048192771 + 212.048192771 white 9 - + - + - kinetics_479_0_ * basal_activity_873_0__Kf * CaMKII_841_0_ + kinetics_451_0_ * basal_activity_846_0__Kf * CaMKII_814_0_ - kinetics_479_0_ - basal_activity_873_0__Kf - CaMKII_841_0_ + kinetics_451_0_ + basal_activity_846_0__Kf + CaMKII_814_0_ - + - + Use K3 = 21.5 uM here from Stemmer and Klee table 3. kb/kf =21.5 * 6e5 so kf = 7.75e-7, kb = 10 @@ -5033,22 +5480,22 @@ 477.941176471 - -212.048192771 + 212.048192771 white 10 - - + + - + - kinetics_479_0_ * CaM_Ca3_bind_Ca_909_0__Kf * Ca_1197_0_*CaM_Ca3_887_0_-kinetics_479_0_ * CaM_Ca3_bind_Ca_909_0__Kb * CaM_Ca4_877_0_ + kinetics_451_0_ * CaM_Ca3_bind_Ca_882_0__Kf * Ca_1170_0_*CaM_Ca3_860_0_-kinetics_451_0_ * CaM_Ca3_bind_Ca_882_0__Kb * CaM_Ca4_850_0_ @@ -5056,26 +5503,26 @@ - kinetics_479_0_ - CaM_Ca3_bind_Ca_909_0__Kf - Ca_1197_0_ - CaM_Ca3_887_0_ + kinetics_451_0_ + CaM_Ca3_bind_Ca_882_0__Kf + Ca_1170_0_ + CaM_Ca3_860_0_ - kinetics_479_0_ - CaM_Ca3_bind_Ca_909_0__Kb - CaM_Ca4_877_0_ + kinetics_451_0_ + CaM_Ca3_bind_Ca_882_0__Kb + CaM_Ca4_850_0_ - - + + - + Surprisingly, no direct info on rates from neurogranin at this time. These rates are based on GAP-43 binding studies. As GAP-43 and neurogranin share near identity in the CaM/PKC binding regions, and also similarity in phosph and dephosph rates, I am borrowing GAP-43 kinetic info. See Alexander et al JBC 262:13 6108-6113 1987 @@ -5084,22 +5531,22 @@ 492.647058824 - -212.048192771 + 212.048192771 white 10 - - + + - + - kinetics_479_0_ * neurogranin_bind_CaM_911_0__Kf * neurogranin_885_0_*CaM_879_0_-kinetics_479_0_ * neurogranin_bind_CaM_911_0__Kb * neurogranin_CaM_881_0_ + kinetics_451_0_ * neurogranin_bind_CaM_884_0__Kf * neurogranin_858_0_*CaM_852_0_-kinetics_451_0_ * neurogranin_bind_CaM_884_0__Kb * neurogranin_CaM_854_0_ @@ -5107,26 +5554,26 @@ - kinetics_479_0_ - neurogranin_bind_CaM_911_0__Kf - neurogranin_885_0_ - CaM_879_0_ + kinetics_451_0_ + neurogranin_bind_CaM_884_0__Kf + neurogranin_858_0_ + CaM_852_0_ - kinetics_479_0_ - neurogranin_bind_CaM_911_0__Kb - neurogranin_CaM_881_0_ + kinetics_451_0_ + neurogranin_bind_CaM_884_0__Kb + neurogranin_CaM_854_0_ - - + + - + This is put in to keep the basal levels of neurogranin* experimentally reasonable. From various papers, specially Ramakers et al JBC 270:23 1995 13892-13898, it looks like the basal level of phosph is between 20 and 40%. I est around 25 % The kf of 0.005 gives around this level at basal PKC activity levels of 0.1 uM active PKC. @@ -5135,37 +5582,37 @@ 507.352941176 - -212.048192771 + 212.048192771 white 10 - + - + - kinetics_479_0_ * dephosph_neurogranin_913_0__Kf * neurogranin_p_883_0_ + kinetics_451_0_ * dephosph_neurogranin_886_0__Kf * neurogranin_p_856_0_ - kinetics_479_0_ - dephosph_neurogranin_913_0__Kf - neurogranin_p_883_0_ + kinetics_451_0_ + dephosph_neurogranin_886_0__Kf + neurogranin_p_856_0_ - + - + Lets use the fast rate consts here. Since the rates are so different, I am not sure whether the order is relevant. These correspond to the TR2C fragment. We use the Martin et al rates here, plus the Drabicowski binding consts. All are scaled by 3X to cell temp. kf = 2e-10 kb = 72 Stemmer _and Klee: K1=.9, K2=1.1. Assume 1.0uM for both. kb/kf=3.6e11. If kb=72, kf = 2e-10 (Exactly the same !) 19 May 2006. Splitting the old CaM-TR2-bind-Ca reaction into two steps, each binding 1 Ca. This improves numerical stability and is conceptually better too. Overall rates are the same, so each kf and kb is the square root of the earlier ones. So kf = 1.125e-4, kb = 8.4853 @@ -5174,22 +5621,22 @@ 522.058823529 - -212.048192771 + 212.048192771 white 10 - - + + - + - kinetics_479_0_ * CaM_bind_Ca_915_0__Kf * Ca_1197_0_*CaM_879_0_-kinetics_479_0_ * CaM_bind_Ca_915_0__Kb * CaM_Ca_907_0_ + kinetics_451_0_ * CaM_bind_Ca_888_0__Kf * Ca_1170_0_*CaM_852_0_-kinetics_451_0_ * CaM_bind_Ca_888_0__Kb * CaM_Ca_880_0_ @@ -5197,26 +5644,26 @@ - kinetics_479_0_ - CaM_bind_Ca_915_0__Kf - Ca_1197_0_ - CaM_879_0_ + kinetics_451_0_ + CaM_bind_Ca_888_0__Kf + Ca_1170_0_ + CaM_852_0_ - kinetics_479_0_ - CaM_bind_Ca_915_0__Kb - CaM_Ca_907_0_ + kinetics_451_0_ + CaM_bind_Ca_888_0__Kb + CaM_Ca_880_0_ - - + + - + K3 = 21.5, K4 = 2.8. Assuming that the K4 step happens first, we get kb/kf = 2.8 uM = 1.68e6 so kf =6e-6 assuming kb = 10 @@ -5225,22 +5672,22 @@ 536.764705882 - -212.048192771 + 212.048192771 white 10 - - + + - + - kinetics_479_0_ * CaM_Ca2_bind_Ca_917_0__Kf * CaM_Ca2_905_0_*Ca_1197_0_-kinetics_479_0_ * CaM_Ca2_bind_Ca_917_0__Kb * CaM_Ca3_887_0_ + kinetics_451_0_ * CaM_Ca2_bind_Ca_890_0__Kf * Ca_1170_0_*CaM_Ca2_878_0_-kinetics_451_0_ * CaM_Ca2_bind_Ca_890_0__Kb * CaM_Ca3_860_0_ @@ -5248,26 +5695,26 @@ - kinetics_479_0_ - CaM_Ca2_bind_Ca_917_0__Kf - CaM_Ca2_905_0_ - Ca_1197_0_ + kinetics_451_0_ + CaM_Ca2_bind_Ca_890_0__Kf + Ca_1170_0_ + CaM_Ca2_878_0_ - kinetics_479_0_ - CaM_Ca2_bind_Ca_917_0__Kb - CaM_Ca3_887_0_ + kinetics_451_0_ + CaM_Ca2_bind_Ca_890_0__Kb + CaM_Ca3_860_0_ - - + + - + Lets use the fast rate consts here. Since the rates are so different, I am not sure whether the order is relevant. These correspond to the TR2C fragment. We use the Martin et al rates here, plus the Drabicowski binding consts. All are scaled by 3X to cell temp. kf = 2e-10 kb = 72 Stemmer _and Klee: K1=.9, K2=1.1. Assume 1.0uM for both. kb/kf=3.6e11. If kb=72, kf = 2e-10 (Exactly the same !) 19 May 2006. Splitting the old CaM-TR2-bind-Ca reaction into two steps, each binding 1 Ca. This improves numerical stability and is conceptually better too. Overall rates are the same, so each kf and kb is the square root of the earlier ones. So kf = 1.125e-4, kb = 8.4853 @@ -5276,22 +5723,22 @@ 551.470588235 - -212.048192771 + 212.048192771 white 10 - - + + - + - kinetics_479_0_ * CaM_Ca_bind_Ca_919_0__Kf * CaM_Ca_907_0_*Ca_1197_0_-kinetics_479_0_ * CaM_Ca_bind_Ca_919_0__Kb * CaM_Ca2_905_0_ + kinetics_451_0_ * CaM_Ca_bind_Ca_892_0__Kf * CaM_Ca_880_0_*Ca_1170_0_-kinetics_451_0_ * CaM_Ca_bind_Ca_892_0__Kb * CaM_Ca2_878_0_ @@ -5299,45 +5746,45 @@ - kinetics_479_0_ - CaM_Ca_bind_Ca_919_0__Kf - CaM_Ca_907_0_ - Ca_1197_0_ + kinetics_451_0_ + CaM_Ca_bind_Ca_892_0__Kf + CaM_Ca_880_0_ + Ca_1170_0_ - kinetics_479_0_ - CaM_Ca_bind_Ca_919_0__Kb - CaM_Ca2_905_0_ + kinetics_451_0_ + CaM_Ca_bind_Ca_892_0__Kb + CaM_Ca2_878_0_ - - + + - + 566.176470588 - -212.048192771 + 212.048192771 white 10 - - + + - + - kinetics_479_0_ * CaMKIII_bind_CaM_Ca4_921_0__Kf * CaMKIII_1425_0_*CaM_Ca4_877_0_-kinetics_479_0_ * CaMKIII_bind_CaM_Ca4_921_0__Kb * CaMKIII_CaM_Ca4_1427_0_ + kinetics_451_0_ * CaMKIII_bind_CaM_Ca4_894_0__Kf * CaM_Ca4_850_0_*CaMKIII_1398_0_-kinetics_451_0_ * CaMKIII_bind_CaM_Ca4_894_0__Kb * CaMKIII_CaM_Ca4_1400_0_ @@ -5345,26 +5792,26 @@ - kinetics_479_0_ - CaMKIII_bind_CaM_Ca4_921_0__Kf - CaMKIII_1425_0_ - CaM_Ca4_877_0_ + kinetics_451_0_ + CaMKIII_bind_CaM_Ca4_894_0__Kf + CaM_Ca4_850_0_ + CaMKIII_1398_0_ - kinetics_479_0_ - CaMKIII_bind_CaM_Ca4_921_0__Kb - CaMKIII_CaM_Ca4_1427_0_ + kinetics_451_0_ + CaMKIII_bind_CaM_Ca4_894_0__Kb + CaMKIII_CaM_Ca4_1400_0_ - - + + - + K inhib = 1nM from Cohen Ann Rev Bioch 1989, 4 nM from Foukes et al Assume 2 nM. kf /kb = 8.333e-4 @@ -5373,22 +5820,22 @@ 595.588235294 - -212.048192771 + 212.048192771 white 11 - - + + - + - kinetics_479_0_ * Inact_PP1_950_0__Kf * I1_p_944_0_*PP1_active_925_0_-kinetics_479_0_ * Inact_PP1_950_0__Kb * PP1_I1_p_946_0_ + kinetics_451_0_ * Inact_PP1_923_0__Kf * PP1_active_898_0_*I1_p_917_0_-kinetics_451_0_ * Inact_PP1_923_0__Kb * PP1_I1_p_919_0_ @@ -5396,26 +5843,26 @@ - kinetics_479_0_ - Inact_PP1_950_0__Kf - I1_p_944_0_ - PP1_active_925_0_ + kinetics_451_0_ + Inact_PP1_923_0__Kf + PP1_active_898_0_ + I1_p_917_0_ - kinetics_479_0_ - Inact_PP1_950_0__Kb - PP1_I1_p_946_0_ + kinetics_451_0_ + Inact_PP1_923_0__Kb + PP1_I1_p_919_0_ - - + + - + Let us assume that the equil in this case is very far over to the right. This is probably safe. @@ -5424,38 +5871,38 @@ 610.294117647 - -212.048192771 + 212.048192771 white 11 - + - - + + - kinetics_479_0_ * dissoc_PP1_I1_952_0__Kf * PP1_I1_948_0_ + kinetics_451_0_ * dissoc_PP1_I1_925_0__Kf * PP1_I1_921_0_ - kinetics_479_0_ - dissoc_PP1_I1_952_0__Kf - PP1_I1_948_0_ + kinetics_451_0_ + dissoc_PP1_I1_925_0__Kf + PP1_I1_921_0_ - + - + This process is probably much more complicated and involves CaM. However, as I can't find detailed info I am bundling this into a single step. Based on Steemer and Klee pg 6863, the Kact is 0.5 uM. kf/kb = 1/(0.5 * 6e5)^2 = 1.11e-11 @@ -5464,22 +5911,22 @@ 742.647058824 - -212.048192771 + 212.048192771 white 12 - - + + - + - kinetics_479_0_ * Ca_bind_CaNAB_Ca2_966_0__Kf * Ca_1197_0_^2*CaNAB_Ca2_958_0_-kinetics_479_0_ * Ca_bind_CaNAB_Ca2_966_0__Kb * CaNAB_Ca4_900_0_ + kinetics_451_0_ * Ca_bind_CaNAB_Ca2_939_0__Kf * Ca_1170_0_^2*CaNAB_Ca2_931_0_-kinetics_451_0_ * Ca_bind_CaNAB_Ca2_939_0__Kb * CaNAB_Ca4_873_0_ @@ -5487,30 +5934,30 @@ - kinetics_479_0_ - Ca_bind_CaNAB_Ca2_966_0__Kf + kinetics_451_0_ + Ca_bind_CaNAB_Ca2_939_0__Kf - Ca_1197_0_ + Ca_1170_0_ 2 - CaNAB_Ca2_958_0_ + CaNAB_Ca2_931_0_ - kinetics_479_0_ - Ca_bind_CaNAB_Ca2_966_0__Kb - CaNAB_Ca4_900_0_ + kinetics_451_0_ + Ca_bind_CaNAB_Ca2_939_0__Kb + CaNAB_Ca4_873_0_ - - + + - + going on the experience with CaM, we put the fast (high affinity) sites first. We only know (Stemmer and Klee) that the affinity is _lessthan_ 70 nM. Assuming 10 nM at first, we get kf = 2.78e-8, kb = 1. Try 20 nM. kf = 7e-9, kb = 1 @@ -5519,22 +5966,22 @@ 757.352941176 - -212.048192771 + 212.048192771 white 12 - - + + - + - kinetics_479_0_ * Ca_bind_CaNAB_968_0__Kf * CaNAB_956_0_*Ca_1197_0_^2-kinetics_479_0_ * Ca_bind_CaNAB_968_0__Kb * CaNAB_Ca2_958_0_ + kinetics_451_0_ * Ca_bind_CaNAB_941_0__Kf * CaNAB_929_0_*Ca_1170_0_^2-kinetics_451_0_ * Ca_bind_CaNAB_941_0__Kb * CaNAB_Ca2_931_0_ @@ -5542,30 +5989,30 @@ - kinetics_479_0_ - Ca_bind_CaNAB_968_0__Kf - CaNAB_956_0_ + kinetics_451_0_ + Ca_bind_CaNAB_941_0__Kf + CaNAB_929_0_ - Ca_1197_0_ + Ca_1170_0_ 2 - kinetics_479_0_ - Ca_bind_CaNAB_968_0__Kb - CaNAB_Ca2_958_0_ + kinetics_451_0_ + Ca_bind_CaNAB_941_0__Kb + CaNAB_Ca2_931_0_ - - + + - + Disabled. See notes for PP2B7.g @@ -5574,22 +6021,22 @@ 772.058823529 - -212.048192771 + 212.048192771 white 12 - - + + - + - kinetics_479_0_ * CaM_Ca2_bind_CaNAB_970_0__Kf * CaM_Ca2_905_0_*CaNAB_Ca4_900_0_-kinetics_479_0_ * CaM_Ca2_bind_CaNAB_970_0__Kb * CaMCa2_CaNAB_962_0_ + kinetics_451_0_ * CaM_Ca2_bind_CaNAB_943_0__Kf * CaNAB_Ca4_873_0_*CaM_Ca2_878_0_-kinetics_451_0_ * CaM_Ca2_bind_CaNAB_943_0__Kb * CaMCa2_CaNAB_935_0_ @@ -5597,45 +6044,45 @@ - kinetics_479_0_ - CaM_Ca2_bind_CaNAB_970_0__Kf - CaM_Ca2_905_0_ - CaNAB_Ca4_900_0_ + kinetics_451_0_ + CaM_Ca2_bind_CaNAB_943_0__Kf + CaNAB_Ca4_873_0_ + CaM_Ca2_878_0_ - kinetics_479_0_ - CaM_Ca2_bind_CaNAB_970_0__Kb - CaMCa2_CaNAB_962_0_ + kinetics_451_0_ + CaM_Ca2_bind_CaNAB_943_0__Kb + CaMCa2_CaNAB_935_0_ - - + + - + 786.764705882 - -212.048192771 + 212.048192771 white 12 - - + + - + - kinetics_479_0_ * CaMCa3_bind_CaNAB_972_0__Kf * CaNAB_Ca4_900_0_*CaM_Ca3_887_0_-kinetics_479_0_ * CaMCa3_bind_CaNAB_972_0__Kb * CaMCa3_CaNAB_960_0_ + kinetics_451_0_ * CaMCa3_bind_CaNAB_945_0__Kf * CaNAB_Ca4_873_0_*CaM_Ca3_860_0_-kinetics_451_0_ * CaMCa3_bind_CaNAB_945_0__Kb * CaMCa3_CaNAB_933_0_ @@ -5643,45 +6090,45 @@ - kinetics_479_0_ - CaMCa3_bind_CaNAB_972_0__Kf - CaNAB_Ca4_900_0_ - CaM_Ca3_887_0_ + kinetics_451_0_ + CaMCa3_bind_CaNAB_945_0__Kf + CaNAB_Ca4_873_0_ + CaM_Ca3_860_0_ - kinetics_479_0_ - CaMCa3_bind_CaNAB_972_0__Kb - CaMCa3_CaNAB_960_0_ + kinetics_451_0_ + CaMCa3_bind_CaNAB_945_0__Kb + CaMCa3_CaNAB_933_0_ - - + + - + 801.470588235 - -212.048192771 + 212.048192771 white 12 - - + + - + - kinetics_479_0_ * CaMCa4_bind_CaNAB_974_0__Kf * CaNAB_Ca4_900_0_*CaM_Ca4_877_0_-kinetics_479_0_ * CaMCa4_bind_CaNAB_974_0__Kb * CaMCa4_CaNAB_964_0_ + kinetics_451_0_ * CaMCa4_bind_CaNAB_947_0__Kf * CaNAB_Ca4_873_0_*CaM_Ca4_850_0_-kinetics_451_0_ * CaMCa4_bind_CaNAB_947_0__Kb * CaMCa4_CaNAB_937_0_ @@ -5689,26 +6136,26 @@ - kinetics_479_0_ - CaMCa4_bind_CaNAB_974_0__Kf - CaNAB_Ca4_900_0_ - CaM_Ca4_877_0_ + kinetics_451_0_ + CaMCa4_bind_CaNAB_947_0__Kf + CaNAB_Ca4_873_0_ + CaM_Ca4_850_0_ - kinetics_479_0_ - CaMCa4_bind_CaNAB_974_0__Kb - CaMCa4_CaNAB_964_0_ + kinetics_451_0_ + CaMCa4_bind_CaNAB_947_0__Kb + CaMCa4_CaNAB_937_0_ - - + + - + Hasler et al FASEB J 6:2734-2741 1992 say Kd =1e-7M for type II, 5.6e-8 M for type I. Take mean which comes to 2e-13 #/cell Smith et al PNAS USA 78:3 1591-1595 1981 have better data. First kf/kb=2.1e7/M = 3.5e-5 (#/cell). Ogreid and Doskeland Febs Lett 129:2 287-292 1981 have figs suggesting time course of complete assoc is _lessthan_ 1 min. @@ -5717,22 +6164,22 @@ 889.705882353 - -212.048192771 + 212.048192771 white 13 - - + + - + - kinetics_479_0_ * cAMP_bind_site_B1_1007_0__Kf * R2C2_989_0_*cAMP_1023_0_-kinetics_479_0_ * cAMP_bind_site_B1_1007_0__Kb * R2C2_cAMP_991_0_ + kinetics_451_0_ * cAMP_bind_site_B1_980_0__Kf * R2C2_962_0_*cAMP_996_0_-kinetics_451_0_ * cAMP_bind_site_B1_980_0__Kb * R2C2_cAMP_964_0_ @@ -5740,26 +6187,26 @@ - kinetics_479_0_ - cAMP_bind_site_B1_1007_0__Kf - R2C2_989_0_ - cAMP_1023_0_ + kinetics_451_0_ + cAMP_bind_site_B1_980_0__Kf + R2C2_962_0_ + cAMP_996_0_ - kinetics_479_0_ - cAMP_bind_site_B1_1007_0__Kb - R2C2_cAMP_991_0_ + kinetics_451_0_ + cAMP_bind_site_B1_980_0__Kb + R2C2_cAMP_964_0_ - - + + - + For now let us set this to the same Km (1e-7M) as site B. This gives kf/kb = .7e-7M * 1e6 / (6e5^2) : 1/(6e5^2) = 2e-13:2.77e-12 Smith et al have better values. They say that this is cooperative, so the consts are now kf/kb =8.3e-4 @@ -5768,22 +6215,22 @@ 904.411764706 - -212.048192771 + 212.048192771 white 13 - - + + - + - kinetics_479_0_ * cAMP_bind_site_B2_1009_0__Kf * cAMP_1023_0_*R2C2_cAMP_991_0_-kinetics_479_0_ * cAMP_bind_site_B2_1009_0__Kb * R2C2_cAMP2_993_0_ + kinetics_451_0_ * cAMP_bind_site_B2_982_0__Kf * cAMP_996_0_*R2C2_cAMP_964_0_-kinetics_451_0_ * cAMP_bind_site_B2_982_0__Kb * R2C2_cAMP2_966_0_ @@ -5791,45 +6238,45 @@ - kinetics_479_0_ - cAMP_bind_site_B2_1009_0__Kf - cAMP_1023_0_ - R2C2_cAMP_991_0_ + kinetics_451_0_ + cAMP_bind_site_B2_982_0__Kf + cAMP_996_0_ + R2C2_cAMP_964_0_ - kinetics_479_0_ - cAMP_bind_site_B2_1009_0__Kb - R2C2_cAMP2_993_0_ + kinetics_451_0_ + cAMP_bind_site_B2_982_0__Kb + R2C2_cAMP2_966_0_ - - + + - + 919.117647059 - -212.048192771 + 212.048192771 white 13 - - + + - + - kinetics_479_0_ * cAMP_bind_site_A1_1011_0__Kf * R2C2_cAMP2_993_0_*cAMP_1023_0_-kinetics_479_0_ * cAMP_bind_site_A1_1011_0__Kb * R2C2_cAMP3_995_0_ + kinetics_451_0_ * cAMP_bind_site_A1_984_0__Kf * cAMP_996_0_*R2C2_cAMP2_966_0_-kinetics_451_0_ * cAMP_bind_site_A1_984_0__Kb * R2C2_cAMP3_968_0_ @@ -5837,45 +6284,45 @@ - kinetics_479_0_ - cAMP_bind_site_A1_1011_0__Kf - R2C2_cAMP2_993_0_ - cAMP_1023_0_ + kinetics_451_0_ + cAMP_bind_site_A1_984_0__Kf + cAMP_996_0_ + R2C2_cAMP2_966_0_ - kinetics_479_0_ - cAMP_bind_site_A1_1011_0__Kb - R2C2_cAMP3_995_0_ + kinetics_451_0_ + cAMP_bind_site_A1_984_0__Kb + R2C2_cAMP3_968_0_ - - + + - + 933.823529412 - -212.048192771 + 212.048192771 white 13 - - + + - + - kinetics_479_0_ * cAMP_bind_site_A2_1013_0__Kf * R2C2_cAMP3_995_0_*cAMP_1023_0_-kinetics_479_0_ * cAMP_bind_site_A2_1013_0__Kb * R2C2_cAMP4_997_0_ + kinetics_451_0_ * cAMP_bind_site_A2_986_0__Kf * R2C2_cAMP3_968_0_*cAMP_996_0_-kinetics_451_0_ * cAMP_bind_site_A2_986_0__Kb * R2C2_cAMP4_970_0_ @@ -5883,26 +6330,26 @@ - kinetics_479_0_ - cAMP_bind_site_A2_1013_0__Kf - R2C2_cAMP3_995_0_ - cAMP_1023_0_ + kinetics_451_0_ + cAMP_bind_site_A2_986_0__Kf + R2C2_cAMP3_968_0_ + cAMP_996_0_ - kinetics_479_0_ - cAMP_bind_site_A2_1013_0__Kb - R2C2_cAMP4_997_0_ + kinetics_451_0_ + cAMP_bind_site_A2_986_0__Kb + R2C2_cAMP4_970_0_ - - + + - + This has to be fast, as the activation of PKA by cAMP is also fast. kf was 10 @@ -5911,22 +6358,22 @@ 948.529411765 - -212.048192771 + 212.048192771 white 13 - + - - + + - kinetics_479_0_ * Release_C1_1015_0__Kf * R2C2_cAMP4_997_0_-kinetics_479_0_ * Release_C1_1015_0__Kb * PKA_active_978_0_*R2C_cAMP4_999_0_ + kinetics_451_0_ * Release_C1_988_0__Kf * R2C2_cAMP4_970_0_-kinetics_451_0_ * Release_C1_988_0__Kb * R2C_cAMP4_972_0_*PKA_active_951_0_ @@ -5934,45 +6381,45 @@ - kinetics_479_0_ - Release_C1_1015_0__Kf - R2C2_cAMP4_997_0_ + kinetics_451_0_ + Release_C1_988_0__Kf + R2C2_cAMP4_970_0_ - kinetics_479_0_ - Release_C1_1015_0__Kb - PKA_active_978_0_ - R2C_cAMP4_999_0_ + kinetics_451_0_ + Release_C1_988_0__Kb + R2C_cAMP4_972_0_ + PKA_active_951_0_ - - + + - + 963.235294118 - -212.048192771 + 212.048192771 white 13 - + - - + + - kinetics_479_0_ * Release_C2_1017_0__Kf * R2C_cAMP4_999_0_-kinetics_479_0_ * Release_C2_1017_0__Kb * R2_cAMP4_1001_0_*PKA_active_978_0_ + kinetics_451_0_ * Release_C2_990_0__Kf * R2C_cAMP4_972_0_-kinetics_451_0_ * Release_C2_990_0__Kb * R2_cAMP4_974_0_*PKA_active_951_0_ @@ -5980,26 +6427,26 @@ - kinetics_479_0_ - Release_C2_1017_0__Kf - R2C_cAMP4_999_0_ + kinetics_451_0_ + Release_C2_990_0__Kf + R2C_cAMP4_972_0_ - kinetics_479_0_ - Release_C2_1017_0__Kb - R2_cAMP4_1001_0_ - PKA_active_978_0_ + kinetics_451_0_ + Release_C2_990_0__Kb + R2_cAMP4_974_0_ + PKA_active_951_0_ - - + + - + This has to be set to zero for matching the expts in vitro. In vivo we need to consider the inhibition though. kf = 1e-5 kb = 1 @@ -6008,22 +6455,22 @@ 977.941176471 - -212.048192771 + 212.048192771 white 13 - - + + - + - kinetics_479_0_ * inhib_PKA_1019_0__Kf * PKA_active_978_0_*PKA_inhibitor_1003_0_-kinetics_479_0_ * inhib_PKA_1019_0__Kb * inhibited_PKA_1005_0_ + kinetics_451_0_ * inhib_PKA_992_0__Kf * PKA_inhibitor_976_0_*PKA_active_951_0_-kinetics_451_0_ * inhib_PKA_992_0__Kb * inhibited_PKA_978_0_ @@ -6031,26 +6478,26 @@ - kinetics_479_0_ - inhib_PKA_1019_0__Kf - PKA_active_978_0_ - PKA_inhibitor_1003_0_ + kinetics_451_0_ + inhib_PKA_992_0__Kf + PKA_inhibitor_976_0_ + PKA_active_951_0_ - kinetics_479_0_ - inhib_PKA_1019_0__Kb - inhibited_PKA_1005_0_ + kinetics_451_0_ + inhib_PKA_992_0__Kb + inhibited_PKA_978_0_ - - + + - + Half-max at 20 nM CaM (Tang et al JBC 266:13 8595-8603 1991 kb/kf = 20 nM = 12000 #/cell so kf = kb/12000 = kb * 8.333e-5 @@ -6059,22 +6506,22 @@ 7.35294117647 - -404.819277108 + 404.819277108 white 14 - - + + - + - kinetics_479_0_ * CaM_bind_AC1_1071_0__Kf * CaM_Ca4_877_0_*AC1_1031_0_-kinetics_479_0_ * CaM_bind_AC1_1071_0__Kb * AC1_CaM_1027_0_ + kinetics_451_0_ * CaM_bind_AC1_1044_0__Kf * CaM_Ca4_850_0_*AC1_1004_0_-kinetics_451_0_ * CaM_bind_AC1_1044_0__Kb * AC1_CaM_1000_0_ @@ -6082,26 +6529,26 @@ - kinetics_479_0_ - CaM_bind_AC1_1071_0__Kf - CaM_Ca4_877_0_ - AC1_1031_0_ + kinetics_451_0_ + CaM_bind_AC1_1044_0__Kf + CaM_Ca4_850_0_ + AC1_1004_0_ - kinetics_479_0_ - CaM_bind_AC1_1071_0__Kb - AC1_CaM_1027_0_ + kinetics_451_0_ + CaM_bind_AC1_1044_0__Kb + AC1_CaM_1000_0_ - - + + - + Random rate. @@ -6110,37 +6557,37 @@ 22.0588235294 - -404.819277108 + 404.819277108 white 14 - + - + - kinetics_479_0_ * dephosph_AC2_1073_0__Kf * AC2_p_1033_0_ + kinetics_451_0_ * dephosph_AC2_1046_0__Kf * AC2_p_1006_0_ - kinetics_479_0_ - dephosph_AC2_1073_0__Kf - AC2_p_1033_0_ + kinetics_451_0_ + dephosph_AC2_1046_0__Kf + AC2_p_1006_0_ - + - + Half-max at around 3nM = kb/kf from fig 5 in Feinstein et al PNAS USA 88 10173-10177 1991 kf = kb/1800 = 5.56e-4 kb Ofer's thesis data indicates it is more like 2 nM. kf = kb/1200 = 8.33e-4 @@ -6149,22 +6596,22 @@ 36.7647058824 - -404.819277108 + 404.819277108 white 14 - - + + - + - kinetics_479_0_ * Gs_bind_AC2_1075_0__Kf * AC2_1041_0_*Gs_alpha_1119_0_-kinetics_479_0_ * Gs_bind_AC2_1075_0__Kb * AC2_Gs_1037_0_ + kinetics_451_0_ * Gs_bind_AC2_1048_0__Kf * Gs_alpha_1092_0_*AC2_1014_0_-kinetics_451_0_ * Gs_bind_AC2_1048_0__Kb * AC2_Gs_1010_0_ @@ -6172,26 +6619,26 @@ - kinetics_479_0_ - Gs_bind_AC2_1075_0__Kf - AC2_1041_0_ - Gs_alpha_1119_0_ + kinetics_451_0_ + Gs_bind_AC2_1048_0__Kf + Gs_alpha_1092_0_ + AC2_1014_0_ - kinetics_479_0_ - Gs_bind_AC2_1075_0__Kb - AC2_Gs_1037_0_ + kinetics_451_0_ + Gs_bind_AC2_1048_0__Kb + AC2_Gs_1010_0_ - - + + - + Half-max 8nM from Tang et al JBC266:13 8595-8603 kb/kf = 8 nM = 4800#/cell so kf = kb * 2.08e-4 @@ -6200,22 +6647,22 @@ 51.4705882353 - -404.819277108 + 404.819277108 white 14 - - + + - + - kinetics_479_0_ * Gs_bind_AC1_1077_0__Kf * Gs_alpha_1119_0_*AC1_1031_0_-kinetics_479_0_ * Gs_bind_AC1_1077_0__Kb * AC1_Gs_1043_0_ + kinetics_451_0_ * Gs_bind_AC1_1050_0__Kf * Gs_alpha_1092_0_*AC1_1004_0_-kinetics_451_0_ * Gs_bind_AC1_1050_0__Kb * AC1_Gs_1016_0_ @@ -6223,26 +6670,26 @@ - kinetics_479_0_ - Gs_bind_AC1_1077_0__Kf - Gs_alpha_1119_0_ - AC1_1031_0_ + kinetics_451_0_ + Gs_bind_AC1_1050_0__Kf + Gs_alpha_1092_0_ + AC1_1004_0_ - kinetics_479_0_ - Gs_bind_AC1_1077_0__Kb - AC1_Gs_1043_0_ + kinetics_451_0_ + Gs_bind_AC1_1050_0__Kb + AC1_Gs_1016_0_ - - + + - + kb/kf = 1.2 nM so kf = kb/720 = 1.3888 * kb. @@ -6251,22 +6698,22 @@ 66.1764705882 - -404.819277108 + 404.819277108 white 14 - - + + - + - kinetics_479_0_ * Gs_bind_AC2_p_1079_0__Kf * AC2_p_1033_0_*Gs_alpha_1119_0_-kinetics_479_0_ * Gs_bind_AC2_p_1079_0__Kb * AC2_p_Gs_1047_0_ + kinetics_451_0_ * Gs_bind_AC2_p_1052_0__Kf * Gs_alpha_1092_0_*AC2_p_1006_0_-kinetics_451_0_ * Gs_bind_AC2_p_1052_0__Kb * AC2_p_Gs_1020_0_ @@ -6274,26 +6721,26 @@ - kinetics_479_0_ - Gs_bind_AC2_p_1079_0__Kf - AC2_p_1033_0_ - Gs_alpha_1119_0_ + kinetics_451_0_ + Gs_bind_AC2_p_1052_0__Kf + Gs_alpha_1092_0_ + AC2_p_1006_0_ - kinetics_479_0_ - Gs_bind_AC2_p_1079_0__Kb - AC2_p_Gs_1047_0_ + kinetics_451_0_ + Gs_bind_AC2_p_1052_0__Kb + AC2_p_Gs_1020_0_ - - + + - + The rates for this are poorly constrained. In adipocytes (probably a different PDE) the dephosphorylation is complete within 15 min, but there are no intermediate time points so it could be much faster. Identity of phosphatase etc is still unknown. @@ -6302,37 +6749,37 @@ 80.8823529412 - -404.819277108 + 404.819277108 white 14 - + - + - kinetics_479_0_ * dephosph_PDE_1081_0__Kf * cAMP_PDE_p_1056_0_ + kinetics_451_0_ * dephosph_PDE_1054_0__Kf * cAMP_PDE_p_1029_0_ - kinetics_479_0_ - dephosph_PDE_1081_0__Kf - cAMP_PDE_p_1056_0_ + kinetics_451_0_ + dephosph_PDE_1054_0__Kf + cAMP_PDE_p_1029_0_ - + - + For olf epi PDE1, affinity is 7 nM. Assume same for brain. Reaction should be pretty fast. Assume kb = 5/sec. Then kf = 5 / (0.007 * 6e5) = 1.2e-3 @@ -6341,22 +6788,22 @@ 95.5882352941 - -404.819277108 + 404.819277108 white 14 - - + + - + - kinetics_479_0_ * CaM_bind_PDE1_1083_0__Kf * CaM_Ca4_877_0_*PDE1_1061_0_-kinetics_479_0_ * CaM_bind_PDE1_1083_0__Kb * CaM_dot_PDE1_1066_0_ + kinetics_451_0_ * CaM_bind_PDE1_1056_0__Kf * CaM_Ca4_850_0_*PDE1_1034_0_-kinetics_451_0_ * CaM_bind_PDE1_1056_0__Kb * CaM_dot_PDE1_1039_0_ @@ -6364,26 +6811,26 @@ - kinetics_479_0_ - CaM_bind_PDE1_1083_0__Kf - CaM_Ca4_877_0_ - PDE1_1061_0_ + kinetics_451_0_ + CaM_bind_PDE1_1056_0__Kf + CaM_Ca4_850_0_ + PDE1_1034_0_ - kinetics_479_0_ - CaM_bind_PDE1_1083_0__Kb - CaM_dot_PDE1_1066_0_ + kinetics_451_0_ + CaM_bind_PDE1_1056_0__Kb + CaM_dot_PDE1_1039_0_ - - + + - + kf = kf from text = 1e7 / M / sec = 10 /uM/sec = 10 / 6e5 / # / sec = 1.67e-5 kb = kr from text = 60 / sec Note that we continue to use uM here since [phenylephrine] is also in uM. From Martin et al FEBS Lett 316:2 191-196 1993 we have Kd = 600 nM Assuming kb = 10/sec, we get kf = 10/(0.6 uM * 6e5) = 2.8e-5 1/sec/# @@ -6392,22 +6839,22 @@ 154.411764706 - -404.819277108 + 404.819277108 white 15 - - + + - + - kinetics_479_0_ * RecLigandBinding_1099_0__Kf * Glutamate_1089_0_*mGluR_1091_0_-kinetics_479_0_ * RecLigandBinding_1099_0__Kb * Rec_Glu_1093_0_ + kinetics_451_0_ * RecLigandBinding_1072_0__Kf * mGluR_1064_0_*Glutamate_1062_0_-kinetics_451_0_ * RecLigandBinding_1072_0__Kb * Rec_Glu_1066_0_ @@ -6415,26 +6862,26 @@ - kinetics_479_0_ - RecLigandBinding_1099_0__Kf - Glutamate_1089_0_ - mGluR_1091_0_ + kinetics_451_0_ + RecLigandBinding_1072_0__Kf + mGluR_1064_0_ + Glutamate_1062_0_ - kinetics_479_0_ - RecLigandBinding_1099_0__Kb - Rec_Glu_1093_0_ + kinetics_451_0_ + RecLigandBinding_1072_0__Kb + Rec_Glu_1066_0_ - - + + - + This is the k1-k2 equivalent for enzyme complex formation in the binding of Rec-Glu to Gq. See Fay et al Biochem 30 5066-5075 1991. kf = 5e-5 which is nearly the same as calculated by Fay et al. (4.67e-5) kb = .04 June 1996: Closer reading of Fay et al suggests that kb _lessthan_= 0.0001, so kf = 1e-8 by detailed balance. This reaction appears to be neglible. @@ -6443,22 +6890,22 @@ 169.117647059 - -404.819277108 + 404.819277108 white 15 - - + + - + - kinetics_479_0_ * Rec_Glu_bind_Gq_1101_0__Kf * Rec_Glu_1093_0_*G_GDP_1117_0_-kinetics_479_0_ * Rec_Glu_bind_Gq_1101_0__Kb * Rec_Glu_Gq_1097_0_ + kinetics_451_0_ * Rec_Glu_bind_Gq_1074_0__Kf * Rec_Glu_1066_0_*G_GDP_1090_0_-kinetics_451_0_ * Rec_Glu_bind_Gq_1074_0__Kb * Rec_Glu_Gq_1070_0_ @@ -6466,26 +6913,26 @@ - kinetics_479_0_ - Rec_Glu_bind_Gq_1101_0__Kf - Rec_Glu_1093_0_ - G_GDP_1117_0_ + kinetics_451_0_ + Rec_Glu_bind_Gq_1074_0__Kf + Rec_Glu_1066_0_ + G_GDP_1090_0_ - kinetics_479_0_ - Rec_Glu_bind_Gq_1101_0__Kb - Rec_Glu_Gq_1097_0_ + kinetics_451_0_ + Rec_Glu_bind_Gq_1074_0__Kb + Rec_Glu_Gq_1070_0_ - - + + - + From Fay et al kb3 = kb = 1.06e-3 which is rather slow. k+1 = kf = 2.8e7 /M/sec= 4.67e-5/sec use 5e-5. However, the Kd from Martin et al may be more appropriate, as this is Glu not the system from Fay. kf = 2.8e-5, kb = 10 Let us compromise. since we have the Fay model, keep kf = k+1 = 2.8e-5. But kb (k-3) is .01 * k-1 from Fay. Scaling by .01, kb = .01 * 10 = 0.1 @@ -6494,22 +6941,22 @@ 183.823529412 - -404.819277108 + 404.819277108 white 15 - - + + - + - kinetics_479_0_ * Glu_bind_Rec_Gq_1103_0__Kf * Glutamate_1089_0_*Rec_Gq_1095_0_-kinetics_479_0_ * Glu_bind_Rec_Gq_1103_0__Kb * Rec_Glu_Gq_1097_0_ + kinetics_451_0_ * Glu_bind_Rec_Gq_1076_0__Kf * Rec_Gq_1068_0_*Glutamate_1062_0_-kinetics_451_0_ * Glu_bind_Rec_Gq_1076_0__Kb * Rec_Glu_Gq_1070_0_ @@ -6517,26 +6964,26 @@ - kinetics_479_0_ - Glu_bind_Rec_Gq_1103_0__Kf - Glutamate_1089_0_ - Rec_Gq_1095_0_ + kinetics_451_0_ + Glu_bind_Rec_Gq_1076_0__Kf + Rec_Gq_1068_0_ + Glutamate_1062_0_ - kinetics_479_0_ - Glu_bind_Rec_Gq_1103_0__Kb - Rec_Glu_Gq_1097_0_ + kinetics_451_0_ + Glu_bind_Rec_Gq_1076_0__Kb + Rec_Glu_Gq_1070_0_ - - + + - + This is the kcat==k3 stage of the Rec-Glu ezymatic activation of Gq. From Berstein et al actiation is at .35 - 0.7/min From Fay et al Biochem 30 5066-5075 1991 kf = .01/sec From Nakamura et al J physiol Lond 474:1 35-41 1994 see time courses. Also (Berstein) 15-40% of gprot is in GTP-bound form on stim. @@ -6545,39 +6992,39 @@ 198.529411765 - -404.819277108 + 404.819277108 white 15 - + - - - + + + - kinetics_479_0_ * Activate_Gq_1105_0__Kf * Rec_Glu_Gq_1097_0_ + kinetics_451_0_ * Activate_Gq_1078_0__Kf * Rec_Glu_Gq_1070_0_ - kinetics_479_0_ - Activate_Gq_1105_0__Kf - Rec_Glu_Gq_1097_0_ + kinetics_451_0_ + Activate_Gq_1078_0__Kf + Rec_Glu_Gq_1070_0_ - + - + Lets try out the same kinetics as the Rec-Glu-bind-Gq This is much too forward. We know that the steady-state amount of Rec-Gq should be 40% of the total amount of receptor. This is for a different receptor, still we can try to match the value. kf = 1e-6 and kb = 1 give 0.333:0.8 which is pretty close. @@ -6586,22 +7033,22 @@ 213.235294118 - -404.819277108 + 404.819277108 white 15 - - + + - + - kinetics_479_0_ * Rec_bind_Gq_1107_0__Kf * mGluR_1091_0_*G_GDP_1117_0_-kinetics_479_0_ * Rec_bind_Gq_1107_0__Kb * Rec_Gq_1095_0_ + kinetics_451_0_ * Rec_bind_Gq_1080_0__Kf * mGluR_1064_0_*G_GDP_1090_0_-kinetics_451_0_ * Rec_bind_Gq_1080_0__Kb * Rec_Gq_1068_0_ @@ -6609,26 +7056,26 @@ - kinetics_479_0_ - Rec_bind_Gq_1107_0__Kf - mGluR_1091_0_ - G_GDP_1117_0_ + kinetics_451_0_ + Rec_bind_Gq_1080_0__Kf + mGluR_1064_0_ + G_GDP_1090_0_ - kinetics_479_0_ - Rec_bind_Gq_1107_0__Kb - Rec_Gq_1095_0_ + kinetics_451_0_ + Rec_bind_Gq_1080_0__Kb + Rec_Gq_1068_0_ - - + + - + kf = kg1 = 0.01/sec, kb = 0. This is the basal exchange of GTP for GDP. @@ -6637,38 +7084,38 @@ 301.470588235 - -404.819277108 + 404.819277108 white 16 - + - - + + - kinetics_479_0_ * Basal_Act_Gq_1121_0__Kf * G_GDP_1117_0_ + kinetics_451_0_ * Basal_Act_Gq_1094_0__Kf * G_GDP_1090_0_ - kinetics_479_0_ - Basal_Act_Gq_1121_0__Kf - G_GDP_1117_0_ + kinetics_451_0_ + Basal_Act_Gq_1094_0__Kf + G_GDP_1090_0_ - + - + kf == kg3 = 1e-5 /cell/sec. As usual, there is no back-reaction kb = 0 @@ -6677,39 +7124,39 @@ 316.176470588 - -404.819277108 + 404.819277108 white 16 - - + + - + - kinetics_479_0_ * Trimerize_G_1123_0__Kf * G_pGDP_1115_0_*BetaGamma_1111_0_ + kinetics_451_0_ * Trimerize_G_1096_0__Kf * G_pGDP_1088_0_*BetaGamma_1084_0_ - kinetics_479_0_ - Trimerize_G_1123_0__Kf - G_pGDP_1115_0_ - BetaGamma_1111_0_ + kinetics_451_0_ + Trimerize_G_1096_0__Kf + G_pGDP_1088_0_ + BetaGamma_1084_0_ - + - + From Berstein et al JBC 267:12 8081-8088 1992, kcat for GTPase activity of Gq is only 0.8/min @@ -6718,56 +7165,56 @@ 330.882352941 - -404.819277108 + 404.819277108 white 16 - + - + - kinetics_479_0_ * Inact_Gq_1125_0__Kf * G_pGTP_1113_0_ + kinetics_451_0_ * Inact_Gq_1098_0__Kf * G_pGTP_1086_0_ - kinetics_479_0_ - Inact_Gq_1125_0__Kf - G_pGTP_1113_0_ + kinetics_451_0_ + Inact_Gq_1098_0__Kf + G_pGTP_1086_0_ - + - + 742.647058824 - -404.819277108 + 404.819277108 white 19 - - + + - + - kinetics_479_0_ * bind_Gab1_1231_0__Kf * Gab1_1222_0_*SHC_p_Grb2_clx_798_0_-kinetics_479_0_ * bind_Gab1_1231_0__Kb * SHC_p_Grb2_Gab1_clx_1224_0_ + kinetics_451_0_ * bind_Gab1_1204_0__Kf * SHC_p_Grb2_clx_771_0_*Gab1_1195_0_-kinetics_451_0_ * bind_Gab1_1204_0__Kb * SHC_p_Grb2_Gab1_clx_1197_0_ @@ -6775,45 +7222,45 @@ - kinetics_479_0_ - bind_Gab1_1231_0__Kf - Gab1_1222_0_ - SHC_p_Grb2_clx_798_0_ + kinetics_451_0_ + bind_Gab1_1204_0__Kf + SHC_p_Grb2_clx_771_0_ + Gab1_1195_0_ - kinetics_479_0_ - bind_Gab1_1231_0__Kb - SHC_p_Grb2_Gab1_clx_1224_0_ + kinetics_451_0_ + bind_Gab1_1204_0__Kb + SHC_p_Grb2_Gab1_clx_1197_0_ - - + + - + 757.352941176 - -404.819277108 + 404.819277108 white 19 - - + + - + - kinetics_479_0_ * PI3K_act_1233_0__Kf * SHC_p_Grb2_Gab1_clx_1224_0_*PI3K_1215_0_-kinetics_479_0_ * PI3K_act_1233_0__Kb * SHC_p_Grb2_Gab1_PI3K_clx_1210_0_ + kinetics_451_0_ * PI3K_act_1206_0__Kf * PI3K_1188_0_*SHC_p_Grb2_Gab1_clx_1197_0_-kinetics_451_0_ * PI3K_act_1206_0__Kb * SHC_p_Grb2_Gab1_PI3K_clx_1183_0_ @@ -6821,44 +7268,44 @@ - kinetics_479_0_ - PI3K_act_1233_0__Kf - SHC_p_Grb2_Gab1_clx_1224_0_ - PI3K_1215_0_ + kinetics_451_0_ + PI3K_act_1206_0__Kf + PI3K_1188_0_ + SHC_p_Grb2_Gab1_clx_1197_0_ - kinetics_479_0_ - PI3K_act_1233_0__Kb - SHC_p_Grb2_Gab1_PI3K_clx_1210_0_ + kinetics_451_0_ + PI3K_act_1206_0__Kb + SHC_p_Grb2_Gab1_PI3K_clx_1183_0_ - - + + - + 772.058823529 - -404.819277108 + 404.819277108 white 19 - + - + - kinetics_479_0_ * basal_PI3K_act_1235_0__Kf * PI3K_1215_0_-kinetics_479_0_ * basal_PI3K_act_1235_0__Kb * PI3K_basal_1217_0_ + kinetics_451_0_ * basal_PI3K_act_1208_0__Kf * PI3K_1188_0_-kinetics_451_0_ * basal_PI3K_act_1208_0__Kb * PI3K_basal_1190_0_ @@ -6866,44 +7313,44 @@ - kinetics_479_0_ - basal_PI3K_act_1235_0__Kf - PI3K_1215_0_ + kinetics_451_0_ + basal_PI3K_act_1208_0__Kf + PI3K_1188_0_ - kinetics_479_0_ - basal_PI3K_act_1235_0__Kb - PI3K_basal_1217_0_ + kinetics_451_0_ + basal_PI3K_act_1208_0__Kb + PI3K_basal_1190_0_ - - + + - + 823.529411765 - -404.819277108 + 404.819277108 white 19 - - + + - + - kinetics_479_0_ * PI3K_bind_Ras_GTP_1242_0__Kf * GTP_Ras_725_0_*PI3K_1215_0_-kinetics_479_0_ * PI3K_bind_Ras_GTP_1242_0__Kb * Ras_GTP_PI3K_1237_0_ + kinetics_451_0_ * PI3K_bind_Ras_GTP_1215_0__Kf * GTP_Ras_698_0_*PI3K_1188_0_-kinetics_451_0_ * PI3K_bind_Ras_GTP_1215_0__Kb * Ras_GTP_PI3K_1210_0_ @@ -6911,45 +7358,45 @@ - kinetics_479_0_ - PI3K_bind_Ras_GTP_1242_0__Kf - GTP_Ras_725_0_ - PI3K_1215_0_ + kinetics_451_0_ + PI3K_bind_Ras_GTP_1215_0__Kf + GTP_Ras_698_0_ + PI3K_1188_0_ - kinetics_479_0_ - PI3K_bind_Ras_GTP_1242_0__Kb - Ras_GTP_PI3K_1237_0_ + kinetics_451_0_ + PI3K_bind_Ras_GTP_1215_0__Kb + Ras_GTP_PI3K_1210_0_ - - + + - + 889.705882353 - -404.819277108 + 404.819277108 white 20 - - + + - + - kinetics_479_0_ * PIP3_bind_AKT_1270_0__Kf * PIP3_1203_0_*AKT_1268_0_-kinetics_479_0_ * PIP3_bind_AKT_1270_0__Kb * PIP3_AKT_1246_0_ + kinetics_451_0_ * PIP3_bind_AKT_1243_0__Kf * PIP3_1176_0_*AKT_1241_0_-kinetics_451_0_ * PIP3_bind_AKT_1243_0__Kb * PIP3_AKT_1219_0_ @@ -6957,45 +7404,45 @@ - kinetics_479_0_ - PIP3_bind_AKT_1270_0__Kf - PIP3_1203_0_ - AKT_1268_0_ + kinetics_451_0_ + PIP3_bind_AKT_1243_0__Kf + PIP3_1176_0_ + AKT_1241_0_ - kinetics_479_0_ - PIP3_bind_AKT_1270_0__Kb - PIP3_AKT_1246_0_ + kinetics_451_0_ + PIP3_bind_AKT_1243_0__Kb + PIP3_AKT_1219_0_ - - + + - + 904.411764706 - -404.819277108 + 404.819277108 white 20 - - + + - + - kinetics_479_0_ * PIP3_bind_PDK1_1272_0__Kf * PIP3_1203_0_*PDK1_1205_0_-kinetics_479_0_ * PIP3_bind_PDK1_1272_0__Kb * PIP3_PDK1_1248_0_ + kinetics_451_0_ * PIP3_bind_PDK1_1245_0__Kf * PIP3_1176_0_*PDK1_1178_0_-kinetics_451_0_ * PIP3_bind_PDK1_1245_0__Kb * PIP3_PDK1_1221_0_ @@ -7003,79 +7450,79 @@ - kinetics_479_0_ - PIP3_bind_PDK1_1272_0__Kf - PIP3_1203_0_ - PDK1_1205_0_ + kinetics_451_0_ + PIP3_bind_PDK1_1245_0__Kf + PIP3_1176_0_ + PDK1_1178_0_ - kinetics_479_0_ - PIP3_bind_PDK1_1272_0__Kb - PIP3_PDK1_1248_0_ + kinetics_451_0_ + PIP3_bind_PDK1_1245_0__Kb + PIP3_PDK1_1221_0_ - - + + - + 7.35294117647 - -597.590361446 + 597.590361446 white 21 - + - + - kinetics_479_0_ * Autophos_TrKB_1292_0__Kf * BDNF_TrKB2_clx_1280_0_ + kinetics_451_0_ * Autophos_TrKB_1265_0__Kf * BDNF_TrKB2_clx_1253_0_ - kinetics_479_0_ - Autophos_TrKB_1292_0__Kf - BDNF_TrKB2_clx_1280_0_ + kinetics_451_0_ + Autophos_TrKB_1265_0__Kf + BDNF_TrKB2_clx_1253_0_ - + - + 22.0588235294 - -597.590361446 + 597.590361446 white 21 - - + + - + - kinetics_479_0_ * Dimeriz_TrKB_1294_0__Kf * BDNF_TrKB_clx_1282_0_*TrKB_1278_0_-kinetics_479_0_ * Dimeriz_TrKB_1294_0__Kb * BDNF_TrKB2_clx_1280_0_ + kinetics_451_0_ * Dimeriz_TrKB_1267_0__Kf * TrKB_1251_0_*BDNF_TrKB_clx_1255_0_-kinetics_451_0_ * Dimeriz_TrKB_1267_0__Kb * BDNF_TrKB2_clx_1253_0_ @@ -7083,45 +7530,45 @@ - kinetics_479_0_ - Dimeriz_TrKB_1294_0__Kf - BDNF_TrKB_clx_1282_0_ - TrKB_1278_0_ + kinetics_451_0_ + Dimeriz_TrKB_1267_0__Kf + TrKB_1251_0_ + BDNF_TrKB_clx_1255_0_ - kinetics_479_0_ - Dimeriz_TrKB_1294_0__Kb - BDNF_TrKB2_clx_1280_0_ + kinetics_451_0_ + Dimeriz_TrKB_1267_0__Kb + BDNF_TrKB2_clx_1253_0_ - - + + - + 36.7647058824 - -597.590361446 + 597.590361446 white 21 - - + + - + - kinetics_479_0_ * Ligand_binding_1296_0__Kf * BDNF_1421_0_*TrKB_1278_0_-kinetics_479_0_ * Ligand_binding_1296_0__Kb * BDNF_TrKB_clx_1282_0_ + kinetics_451_0_ * Ligand_binding_1269_0__Kf * BDNF_1394_0_*TrKB_1251_0_-kinetics_451_0_ * Ligand_binding_1269_0__Kb * BDNF_TrKB_clx_1255_0_ @@ -7129,78 +7576,78 @@ - kinetics_479_0_ - Ligand_binding_1296_0__Kf - BDNF_1421_0_ - TrKB_1278_0_ + kinetics_451_0_ + Ligand_binding_1269_0__Kf + BDNF_1394_0_ + TrKB_1251_0_ - kinetics_479_0_ - Ligand_binding_1296_0__Kb - BDNF_TrKB_clx_1282_0_ + kinetics_451_0_ + Ligand_binding_1269_0__Kb + BDNF_TrKB_clx_1255_0_ - - + + - + 51.4705882353 - -597.590361446 + 597.590361446 white 21 - + - + - kinetics_479_0_ * LR_Internalize_1298_0__Kf * BDNF_TrKB2_p_clx_1284_0_ + kinetics_451_0_ * LR_Internalize_1271_0__Kf * BDNF_TrKB2_p_clx_1257_0_ - kinetics_479_0_ - LR_Internalize_1298_0__Kf - BDNF_TrKB2_p_clx_1284_0_ + kinetics_451_0_ + LR_Internalize_1271_0__Kf + BDNF_TrKB2_p_clx_1257_0_ - + - + 66.1764705882 - -597.590361446 + 597.590361446 white 21 - + - + - kinetics_479_0_ * LR_cycling_1300_0__Kf * Int_BDNF_TrKB2_p_clx_1276_0_-kinetics_479_0_ * LR_cycling_1300_0__Kb * TrKB_1278_0_ + kinetics_451_0_ * LR_cycling_1273_0__Kf * Int_BDNF_TrKB2_p_clx_1249_0_-kinetics_451_0_ * LR_cycling_1273_0__Kb * TrKB_1251_0_ @@ -7208,44 +7655,44 @@ - kinetics_479_0_ - LR_cycling_1300_0__Kf - Int_BDNF_TrKB2_p_clx_1276_0_ + kinetics_451_0_ + LR_cycling_1273_0__Kf + Int_BDNF_TrKB2_p_clx_1249_0_ - kinetics_479_0_ - LR_cycling_1300_0__Kb - TrKB_1278_0_ + kinetics_451_0_ + LR_cycling_1273_0__Kb + TrKB_1251_0_ - - + + - + 154.411764706 - -597.590361446 + 597.590361446 white 22 - - + + - + - kinetics_479_0_ * Rheb_GTP_bind_TORclx_1321_0__Kf * Rheb_GTP_1304_0_*TOR_clx_1308_0_-kinetics_479_0_ * Rheb_GTP_bind_TORclx_1321_0__Kb * TOR_Rheb_GTP_clx_1310_0_ + kinetics_451_0_ * Rheb_GTP_bind_TORclx_1294_0__Kf * TOR_clx_1281_0_*Rheb_GTP_1277_0_-kinetics_451_0_ * Rheb_GTP_bind_TORclx_1294_0__Kb * TOR_Rheb_GTP_clx_1283_0_ @@ -7253,147 +7700,147 @@ - kinetics_479_0_ - Rheb_GTP_bind_TORclx_1321_0__Kf - Rheb_GTP_1304_0_ - TOR_clx_1308_0_ + kinetics_451_0_ + Rheb_GTP_bind_TORclx_1294_0__Kf + TOR_clx_1281_0_ + Rheb_GTP_1277_0_ - kinetics_479_0_ - Rheb_GTP_bind_TORclx_1321_0__Kb - TOR_Rheb_GTP_clx_1310_0_ + kinetics_451_0_ + Rheb_GTP_bind_TORclx_1294_0__Kb + TOR_Rheb_GTP_clx_1283_0_ - - + + - + 169.117647059 - -597.590361446 + 597.590361446 white 22 - + - + - kinetics_479_0_ * GDP_to_GTP_1323_0__Kf * Rheb_GDP_1306_0_ + kinetics_451_0_ * GDP_to_GTP_1296_0__Kf * Rheb_GDP_1279_0_ - kinetics_479_0_ - GDP_to_GTP_1323_0__Kf - Rheb_GDP_1306_0_ + kinetics_451_0_ + GDP_to_GTP_1296_0__Kf + Rheb_GDP_1279_0_ - + - + 301.470588235 - -597.590361446 + 597.590361446 white 23 - + - + - kinetics_479_0_ * S6_dephosph_1349_0__Kf * _40S_1497_0_ + kinetics_451_0_ * S6_dephosph_1322_0__Kf * _40S_1470_0_ - kinetics_479_0_ - S6_dephosph_1349_0__Kf - _40S_1497_0_ + kinetics_451_0_ + S6_dephosph_1322_0__Kf + _40S_1470_0_ - + - + 316.176470588 - -597.590361446 + 597.590361446 white 23 - + - + - kinetics_479_0_ * basal_S6K_1351_0__Kf * S6K_1329_0_ + kinetics_451_0_ * basal_S6K_1324_0__Kf * S6K_1302_0_ - kinetics_479_0_ - basal_S6K_1351_0__Kf - S6K_1329_0_ + kinetics_451_0_ + basal_S6K_1324_0__Kf + S6K_1302_0_ - + - + 448.529411765 - -597.590361446 + 597.590361446 white 24 - - + + - + - kinetics_479_0_ * eIF4E_bind_BP2_1367_0__Kf * _4E_BP_1355_0_*eIF4E_1443_0_-kinetics_479_0_ * eIF4E_bind_BP2_1367_0__Kb * eIF4E_BP_1359_0_ + kinetics_451_0_ * eIF4E_bind_BP2_1340_0__Kf * _4E_BP_1328_0_*eIF4E_1416_0_-kinetics_451_0_ * eIF4E_bind_BP2_1340_0__Kb * eIF4E_BP_1332_0_ @@ -7401,45 +7848,45 @@ - kinetics_479_0_ - eIF4E_bind_BP2_1367_0__Kf - _4E_BP_1355_0_ - eIF4E_1443_0_ + kinetics_451_0_ + eIF4E_bind_BP2_1340_0__Kf + _4E_BP_1328_0_ + eIF4E_1416_0_ - kinetics_479_0_ - eIF4E_bind_BP2_1367_0__Kb - eIF4E_BP_1359_0_ + kinetics_451_0_ + eIF4E_bind_BP2_1340_0__Kb + eIF4E_BP_1332_0_ - - + + - + 463.235294118 - -597.590361446 + 597.590361446 white 24 - + - - + + - kinetics_479_0_ * eIF4E_BP2_disso_1369_0__Kf * eIF4E_BP_t37_46_s65_1363_0_-kinetics_479_0_ * eIF4E_BP2_disso_1369_0__Kb * eIF4E_1443_0_*_4E_BP_t37_46_s65_1357_0_ + kinetics_451_0_ * eIF4E_BP2_disso_1342_0__Kf * eIF4E_BP_t37_46_s65_1336_0_-kinetics_451_0_ * eIF4E_BP2_disso_1342_0__Kb * eIF4E_1416_0_*_4E_BP_t37_46_s65_1330_0_ @@ -7447,45 +7894,45 @@ - kinetics_479_0_ - eIF4E_BP2_disso_1369_0__Kf - eIF4E_BP_t37_46_s65_1363_0_ + kinetics_451_0_ + eIF4E_BP2_disso_1342_0__Kf + eIF4E_BP_t37_46_s65_1336_0_ - kinetics_479_0_ - eIF4E_BP2_disso_1369_0__Kb - eIF4E_1443_0_ - _4E_BP_t37_46_s65_1357_0_ + kinetics_451_0_ + eIF4E_BP2_disso_1342_0__Kb + eIF4E_1416_0_ + _4E_BP_t37_46_s65_1330_0_ - - + + - + 477.941176471 - -597.590361446 + 597.590361446 white 24 - + - - + + - kinetics_479_0_ * eIF4E_BP_disso_1371_0__Kf * eIF4E_BP_thr37_46_1361_0_-kinetics_479_0_ * eIF4E_BP_disso_1371_0__Kb * eIF4E_1443_0_*_4E_BP_t37_46_1365_0_ + kinetics_451_0_ * eIF4E_BP_disso_1344_0__Kf * eIF4E_BP_thr37_46_1334_0_-kinetics_451_0_ * eIF4E_BP_disso_1344_0__Kb * eIF4E_1416_0_*_4E_BP_t37_46_1338_0_ @@ -7493,45 +7940,45 @@ - kinetics_479_0_ - eIF4E_BP_disso_1371_0__Kf - eIF4E_BP_thr37_46_1361_0_ + kinetics_451_0_ + eIF4E_BP_disso_1344_0__Kf + eIF4E_BP_thr37_46_1334_0_ - kinetics_479_0_ - eIF4E_BP_disso_1371_0__Kb - eIF4E_1443_0_ - _4E_BP_t37_46_1365_0_ + kinetics_451_0_ + eIF4E_BP_disso_1344_0__Kb + eIF4E_1416_0_ + _4E_BP_t37_46_1338_0_ - - + + - + 595.588235294 - -597.590361446 + 597.590361446 white 25 - - + + - + - kinetics_479_0_ * Q_binds_R_1383_0__Kf * _40S_1497_0_*Quaternary_clx_1379_0_-kinetics_479_0_ * Q_binds_R_1383_0__Kb * Q_dot_R_1375_0_ + kinetics_451_0_ * Q_binds_R_1356_0__Kf * Quaternary_clx_1352_0_*_40S_1470_0_-kinetics_451_0_ * Q_binds_R_1356_0__Kb * Q_dot_R_1348_0_ @@ -7539,45 +7986,45 @@ - kinetics_479_0_ - Q_binds_R_1383_0__Kf - _40S_1497_0_ - Quaternary_clx_1379_0_ + kinetics_451_0_ + Q_binds_R_1356_0__Kf + Quaternary_clx_1352_0_ + _40S_1470_0_ - kinetics_479_0_ - Q_binds_R_1383_0__Kb - Q_dot_R_1375_0_ + kinetics_451_0_ + Q_binds_R_1356_0__Kb + Q_dot_R_1348_0_ - - + + - + 610.294117647 - -597.590361446 + 597.590361446 white 25 - - + + - + - kinetics_479_0_ * QR_binds_M_1385_0__Kf * eIF4F_mRNA_clx_1455_0_*Q_dot_R_1375_0_-kinetics_479_0_ * QR_binds_M_1385_0__Kb * _43Scomplex_1381_0_ + kinetics_451_0_ * QR_binds_M_1358_0__Kf * eIF4F_mRNA_clx_1428_0_*Q_dot_R_1348_0_-kinetics_451_0_ * QR_binds_M_1358_0__Kb * _43Scomplex_1354_0_ @@ -7585,45 +8032,45 @@ - kinetics_479_0_ - QR_binds_M_1385_0__Kf - eIF4F_mRNA_clx_1455_0_ - Q_dot_R_1375_0_ + kinetics_451_0_ + QR_binds_M_1358_0__Kf + eIF4F_mRNA_clx_1428_0_ + Q_dot_R_1348_0_ - kinetics_479_0_ - QR_binds_M_1385_0__Kb - _43Scomplex_1381_0_ + kinetics_451_0_ + QR_binds_M_1358_0__Kb + _43Scomplex_1354_0_ - - + + - + 625.0 - -597.590361446 + 597.590361446 white 25 - - + + - + - kinetics_479_0_ * R_binds_M_1387_0__Kf * _40S_1497_0_*eIF4F_mRNA_clx_1455_0_-kinetics_479_0_ * R_binds_M_1387_0__Kb * RM_1377_0_ + kinetics_451_0_ * R_binds_M_1360_0__Kf * eIF4F_mRNA_clx_1428_0_*_40S_1470_0_-kinetics_451_0_ * R_binds_M_1360_0__Kb * RM_1350_0_ @@ -7631,45 +8078,45 @@ - kinetics_479_0_ - R_binds_M_1387_0__Kf - _40S_1497_0_ - eIF4F_mRNA_clx_1455_0_ + kinetics_451_0_ + R_binds_M_1360_0__Kf + eIF4F_mRNA_clx_1428_0_ + _40S_1470_0_ - kinetics_479_0_ - R_binds_M_1387_0__Kb - RM_1377_0_ + kinetics_451_0_ + R_binds_M_1360_0__Kb + RM_1350_0_ - - + + - + 639.705882353 - -597.590361446 + 597.590361446 white 25 - - + + - + - kinetics_479_0_ * RM_binds_Q_1389_0__Kf * RM_1377_0_*Quaternary_clx_1379_0_-kinetics_479_0_ * RM_binds_Q_1389_0__Kb * _43Scomplex_1381_0_ + kinetics_451_0_ * RM_binds_Q_1362_0__Kf * Quaternary_clx_1352_0_*RM_1350_0_-kinetics_451_0_ * RM_binds_Q_1362_0__Kb * _43Scomplex_1354_0_ @@ -7677,44 +8124,44 @@ - kinetics_479_0_ - RM_binds_Q_1389_0__Kf - RM_1377_0_ - Quaternary_clx_1379_0_ + kinetics_451_0_ + RM_binds_Q_1362_0__Kf + Quaternary_clx_1352_0_ + RM_1350_0_ - kinetics_479_0_ - RM_binds_Q_1389_0__Kb - _43Scomplex_1381_0_ + kinetics_451_0_ + RM_binds_Q_1362_0__Kb + _43Scomplex_1354_0_ - - + + - + 742.647058824 - -597.590361446 + 597.590361446 white 26 - + - + - kinetics_479_0_ * pep_elongation_1409_0__Kf * peptide_1395_0_-kinetics_479_0_ * pep_elongation_1409_0__Kb * protein_1399_0_ + kinetics_451_0_ * pep_elongation_1382_0__Kf * peptide_1368_0_-kinetics_451_0_ * pep_elongation_1382_0__Kb * protein_1372_0_ @@ -7722,77 +8169,77 @@ - kinetics_479_0_ - pep_elongation_1409_0__Kf - peptide_1395_0_ + kinetics_451_0_ + pep_elongation_1382_0__Kf + peptide_1368_0_ - kinetics_479_0_ - pep_elongation_1409_0__Kb - protein_1399_0_ + kinetics_451_0_ + pep_elongation_1382_0__Kb + protein_1372_0_ - - + + - + 757.352941176 - -597.590361446 + 597.590361446 white 26 - + - + - kinetics_479_0_ * protein_deg_1411_0__Kf * protein_1399_0_ + kinetics_451_0_ * protein_deg_1384_0__Kf * protein_1372_0_ - kinetics_479_0_ - protein_deg_1411_0__Kf - protein_1399_0_ + kinetics_451_0_ + protein_deg_1384_0__Kf + protein_1372_0_ - + - + 772.058823529 - -597.590361446 + 597.590361446 white 26 - + - + - kinetics_479_0_ * rad_pep_elongation_1413_0__Kf * rad_peptide_1403_0_-kinetics_479_0_ * rad_pep_elongation_1413_0__Kb * rad_protein_1405_0_ + kinetics_451_0_ * rad_pep_elongation_1386_0__Kf * rad_peptide_1376_0_-kinetics_451_0_ * rad_pep_elongation_1386_0__Kb * rad_protein_1378_0_ @@ -7800,146 +8247,146 @@ - kinetics_479_0_ - rad_pep_elongation_1413_0__Kf - rad_peptide_1403_0_ + kinetics_451_0_ + rad_pep_elongation_1386_0__Kf + rad_peptide_1376_0_ - kinetics_479_0_ - rad_pep_elongation_1413_0__Kb - rad_protein_1405_0_ + kinetics_451_0_ + rad_pep_elongation_1386_0__Kb + rad_protein_1378_0_ - - + + - + 786.764705882 - -597.590361446 + 597.590361446 white 26 - + - + - kinetics_479_0_ * rad_protein_deg_1415_0__Kf * rad_protein_1405_0_ + kinetics_451_0_ * rad_protein_deg_1388_0__Kf * rad_protein_1378_0_ - kinetics_479_0_ - rad_protein_deg_1415_0__Kf - rad_protein_1405_0_ + kinetics_451_0_ + rad_protein_deg_1388_0__Kf + rad_protein_1378_0_ - + - + 801.470588235 - -597.590361446 + 597.590361446 white 26 - + - + - kinetics_479_0_ * labelling_1417_0__Kf * AA_1393_0_ + kinetics_451_0_ * labelling_1390_0__Kf * AA_1366_0_ - kinetics_479_0_ - labelling_1417_0__Kf - AA_1393_0_ + kinetics_451_0_ + labelling_1390_0__Kf + AA_1366_0_ - + - + 7.35294117647 - -790.361445783 + 790.361445783 white 28 - + - + - kinetics_479_0_ * CaMKIII_dephospho_1439_0__Kf * CaMKIII_p_1437_0_ + kinetics_451_0_ * CaMKIII_dephospho_1412_0__Kf * CaMKIII_p_1410_0_ - kinetics_479_0_ - CaMKIII_dephospho_1439_0__Kf - CaMKIII_p_1437_0_ + kinetics_451_0_ + CaMKIII_dephospho_1412_0__Kf + CaMKIII_p_1410_0_ - + - + 154.411764706 - -790.361445783 + 790.361445783 white 29 - - + + - + - kinetics_479_0_ * eIF4F_clx_1457_0__Kf * eIF4E_1443_0_*eIF4G_A_clx_1445_0_-kinetics_479_0_ * eIF4F_clx_1457_0__Kb * eIF4F_1451_0_ + kinetics_451_0_ * eIF4F_clx_1430_0__Kf * eIF4E_1416_0_*eIF4G_A_clx_1418_0_-kinetics_451_0_ * eIF4F_clx_1430_0__Kb * eIF4F_1424_0_ @@ -7947,45 +8394,45 @@ - kinetics_479_0_ - eIF4F_clx_1457_0__Kf - eIF4E_1443_0_ - eIF4G_A_clx_1445_0_ + kinetics_451_0_ + eIF4F_clx_1430_0__Kf + eIF4E_1416_0_ + eIF4G_A_clx_1418_0_ - kinetics_479_0_ - eIF4F_clx_1457_0__Kb - eIF4F_1451_0_ + kinetics_451_0_ + eIF4F_clx_1430_0__Kb + eIF4F_1424_0_ - - + + - + 169.117647059 - -790.361445783 + 790.361445783 white 29 - - + + - + - kinetics_479_0_ * eIF4G_A_clx_formation_1459_0__Kf * eIF4G_1449_0_*eIF4A_1447_0_-kinetics_479_0_ * eIF4G_A_clx_formation_1459_0__Kb * eIF4G_A_clx_1445_0_ + kinetics_451_0_ * eIF4G_A_clx_formation_1432_0__Kf * eIF4A_1420_0_*eIF4G_1422_0_-kinetics_451_0_ * eIF4G_A_clx_formation_1432_0__Kb * eIF4G_A_clx_1418_0_ @@ -7993,45 +8440,45 @@ - kinetics_479_0_ - eIF4G_A_clx_formation_1459_0__Kf - eIF4G_1449_0_ - eIF4A_1447_0_ + kinetics_451_0_ + eIF4G_A_clx_formation_1432_0__Kf + eIF4A_1420_0_ + eIF4G_1422_0_ - kinetics_479_0_ - eIF4G_A_clx_formation_1459_0__Kb - eIF4G_A_clx_1445_0_ + kinetics_451_0_ + eIF4G_A_clx_formation_1432_0__Kb + eIF4G_A_clx_1418_0_ - - + + - + 183.823529412 - -790.361445783 + 790.361445783 white 29 - - + + - + - kinetics_479_0_ * eIF4F_mRNA_clx_formation_1461_0__Kf * eIF4F_1451_0_*mRNA_1453_0_-kinetics_479_0_ * eIF4F_mRNA_clx_formation_1461_0__Kb * eIF4F_mRNA_clx_1455_0_ + kinetics_451_0_ * eIF4F_mRNA_clx_formation_1434_0__Kf * eIF4F_1424_0_*mRNA_1426_0_-kinetics_451_0_ * eIF4F_mRNA_clx_formation_1434_0__Kb * eIF4F_mRNA_clx_1428_0_ @@ -8039,45 +8486,45 @@ - kinetics_479_0_ - eIF4F_mRNA_clx_formation_1461_0__Kf - eIF4F_1451_0_ - mRNA_1453_0_ + kinetics_451_0_ + eIF4F_mRNA_clx_formation_1434_0__Kf + eIF4F_1424_0_ + mRNA_1426_0_ - kinetics_479_0_ - eIF4F_mRNA_clx_formation_1461_0__Kb - eIF4F_mRNA_clx_1455_0_ + kinetics_451_0_ + eIF4F_mRNA_clx_formation_1434_0__Kb + eIF4F_mRNA_clx_1428_0_ - - + + - + 301.470588235 - -790.361445783 + 790.361445783 white 30 - - + + - + - kinetics_479_0_ * elongation_1489_0__Kf * eEF2_1465_0_*_80S_ribos_clx_1479_0_-kinetics_479_0_ * elongation_1489_0__Kb * Translation_clx_1471_0_ + kinetics_451_0_ * elongation_1462_0__Kf * _80S_ribos_clx_1452_0_*eEF2_1438_0_-kinetics_451_0_ * elongation_1462_0__Kb * Translation_clx_1444_0_ @@ -8085,45 +8532,45 @@ - kinetics_479_0_ - elongation_1489_0__Kf - eEF2_1465_0_ - _80S_ribos_clx_1479_0_ + kinetics_451_0_ + elongation_1462_0__Kf + _80S_ribos_clx_1452_0_ + eEF2_1438_0_ - kinetics_479_0_ - elongation_1489_0__Kb - Translation_clx_1471_0_ + kinetics_451_0_ + elongation_1462_0__Kb + Translation_clx_1444_0_ - - + + - + 316.176470588 - -790.361445783 + 790.361445783 white 30 - - + + - + - kinetics_479_0_ * activation_1491_0__Kf * _43Scomplex_1381_0_*_60S_R_1469_0_-kinetics_479_0_ * activation_1491_0__Kb * _80S_ribos_clx_1479_0_ + kinetics_451_0_ * activation_1464_0__Kf * _43Scomplex_1354_0_*_60S_R_1442_0_-kinetics_451_0_ * activation_1464_0__Kb * _80S_ribos_clx_1452_0_ @@ -8131,79 +8578,79 @@ - kinetics_479_0_ - activation_1491_0__Kf - _43Scomplex_1381_0_ - _60S_R_1469_0_ + kinetics_451_0_ + activation_1464_0__Kf + _43Scomplex_1354_0_ + _60S_R_1442_0_ - kinetics_479_0_ - activation_1491_0__Kb - _80S_ribos_clx_1479_0_ + kinetics_451_0_ + activation_1464_0__Kb + _80S_ribos_clx_1452_0_ - - + + - + 595.588235294 - -790.361445783 + 790.361445783 white 32 - + - + - kinetics_479_0_ * TSC1_TSC2_dephospho_1513_0__Kf * TSC1_TSC2_p_1506_0_ + kinetics_451_0_ * TSC1_TSC2_dephospho_1486_0__Kf * TSC1_TSC2_p_1479_0_ - kinetics_479_0_ - TSC1_TSC2_dephospho_1513_0__Kf - TSC1_TSC2_p_1506_0_ + kinetics_451_0_ + TSC1_TSC2_dephospho_1486_0__Kf + TSC1_TSC2_p_1479_0_ - + - + 742.647058824 - -790.361445783 + 790.361445783 white 33 - - + + - + - kinetics_479_0_ * L_dot_mGluR_HomerBinding_1530_0__Kf * Rec_Glu_1093_0_*Homer_1517_0_-kinetics_479_0_ * L_dot_mGluR_HomerBinding_1530_0__Kb * L_dot_mGluR_p_dot_Homer_1519_0_ + kinetics_451_0_ * L_dot_mGluR_HomerBinding_1503_0__Kf * Rec_Glu_1066_0_*Homer_1490_0_-kinetics_451_0_ * L_dot_mGluR_HomerBinding_1503_0__Kb * L_dot_mGluR_p_dot_Homer_1492_0_ @@ -8211,45 +8658,45 @@ - kinetics_479_0_ - L_dot_mGluR_HomerBinding_1530_0__Kf - Rec_Glu_1093_0_ - Homer_1517_0_ + kinetics_451_0_ + L_dot_mGluR_HomerBinding_1503_0__Kf + Rec_Glu_1066_0_ + Homer_1490_0_ - kinetics_479_0_ - L_dot_mGluR_HomerBinding_1530_0__Kb - L_dot_mGluR_p_dot_Homer_1519_0_ + kinetics_451_0_ + L_dot_mGluR_HomerBinding_1503_0__Kb + L_dot_mGluR_p_dot_Homer_1492_0_ - - + + - + 757.352941176 - -790.361445783 + 790.361445783 white 33 - - + + - + - kinetics_479_0_ * L_dot_mGluR_dot_Homer_PIKE_Binding_1532_0__Kf * PIKE_L_1523_0_*L_dot_mGluR_p_dot_Homer_1519_0_-kinetics_479_0_ * L_dot_mGluR_dot_Homer_PIKE_Binding_1532_0__Kb * L_dot_mGluR_p_dot_Homer_dot_PIKE_L_1521_0_ + kinetics_451_0_ * L_dot_mGluR_dot_Homer_PIKE_Binding_1505_0__Kf * PIKE_L_1496_0_*L_dot_mGluR_p_dot_Homer_1492_0_-kinetics_451_0_ * L_dot_mGluR_dot_Homer_PIKE_Binding_1505_0__Kb * L_dot_mGluR_p_dot_Homer_dot_PIKE_L_1494_0_ @@ -8257,45 +8704,45 @@ - kinetics_479_0_ - L_dot_mGluR_dot_Homer_PIKE_Binding_1532_0__Kf - PIKE_L_1523_0_ - L_dot_mGluR_p_dot_Homer_1519_0_ + kinetics_451_0_ + L_dot_mGluR_dot_Homer_PIKE_Binding_1505_0__Kf + PIKE_L_1496_0_ + L_dot_mGluR_p_dot_Homer_1492_0_ - kinetics_479_0_ - L_dot_mGluR_dot_Homer_PIKE_Binding_1532_0__Kb - L_dot_mGluR_p_dot_Homer_dot_PIKE_L_1521_0_ + kinetics_451_0_ + L_dot_mGluR_dot_Homer_PIKE_Binding_1505_0__Kb + L_dot_mGluR_p_dot_Homer_dot_PIKE_L_1494_0_ - - + + - + 772.058823529 - -790.361445783 + 790.361445783 white 33 - - + + - + - kinetics_479_0_ * L_dot_mGluR_dot_Homer_dot_PIKE_PI3K_Binding_1534_0__Kf * L_dot_mGluR_p_dot_Homer_dot_PIKE_L_1521_0_*PI3K_1215_0_-kinetics_479_0_ * L_dot_mGluR_dot_Homer_dot_PIKE_PI3K_Binding_1534_0__Kb * L_dot_mGluR_p_dot_Homer_dot_PIKE_L_dot_PI3K_1525_0_ + kinetics_451_0_ * L_dot_mGluR_dot_Homer_dot_PIKE_PI3K_Binding_1507_0__Kf * PI3K_1188_0_*L_dot_mGluR_p_dot_Homer_dot_PIKE_L_1494_0_-kinetics_451_0_ * L_dot_mGluR_dot_Homer_dot_PIKE_PI3K_Binding_1507_0__Kb * L_dot_mGluR_p_dot_Homer_dot_PIKE_L_dot_PI3K_1498_0_ @@ -8303,26 +8750,26 @@ - kinetics_479_0_ - L_dot_mGluR_dot_Homer_dot_PIKE_PI3K_Binding_1534_0__Kf - L_dot_mGluR_p_dot_Homer_dot_PIKE_L_1521_0_ - PI3K_1215_0_ + kinetics_451_0_ + L_dot_mGluR_dot_Homer_dot_PIKE_PI3K_Binding_1507_0__Kf + PI3K_1188_0_ + L_dot_mGluR_p_dot_Homer_dot_PIKE_L_1494_0_ - kinetics_479_0_ - L_dot_mGluR_dot_Homer_dot_PIKE_PI3K_Binding_1534_0__Kb - L_dot_mGluR_p_dot_Homer_dot_PIKE_L_dot_PI3K_1525_0_ + kinetics_451_0_ + L_dot_mGluR_dot_Homer_dot_PIKE_PI3K_Binding_1507_0__Kb + L_dot_mGluR_p_dot_Homer_dot_PIKE_L_dot_PI3K_1498_0_ - - + + - + Heitzler,2012 @@ -8331,22 +8778,22 @@ 889.705882353 - -790.361445783 + 790.361445783 white 34 - - + + - + - kinetics_479_0_ * mGluR_barr2_assoc_1557_0__Kf * barr2_1545_0_*L_dot_mGluR_p_1543_0_-kinetics_479_0_ * mGluR_barr2_assoc_1557_0__Kb * L_dot_mGluR_p_dot_barr2_1549_0_ + kinetics_451_0_ * mGluR_barr2_assoc_1530_0__Kf * L_dot_mGluR_p_1516_0_*barr2_1518_0_-kinetics_451_0_ * mGluR_barr2_assoc_1530_0__Kb * L_dot_mGluR_p_dot_barr2_1522_0_ @@ -8354,26 +8801,26 @@ - kinetics_479_0_ - mGluR_barr2_assoc_1557_0__Kf - barr2_1545_0_ - L_dot_mGluR_p_1543_0_ + kinetics_451_0_ + mGluR_barr2_assoc_1530_0__Kf + L_dot_mGluR_p_1516_0_ + barr2_1518_0_ - kinetics_479_0_ - mGluR_barr2_assoc_1557_0__Kb - L_dot_mGluR_p_dot_barr2_1549_0_ + kinetics_451_0_ + mGluR_barr2_assoc_1530_0__Kb + L_dot_mGluR_p_dot_barr2_1522_0_ - - + + - + Rate based on internalization time after beta-arrestin binding. According to Mundell SJ et al., 2001, t(1/2) ~ 1.9(+/-)0.4 min. Therefore, kf =0.005 to 0.0077/s @@ -8382,106 +8829,106 @@ 904.411764706 - -790.361445783 + 790.361445783 white 34 - + - + - kinetics_479_0_ * mGluR_internalize_1559_0__Kf * mGluR_p_dot_barr2_1555_0_ + kinetics_451_0_ * mGluR_internalize_1532_0__Kf * mGluR_p_dot_barr2_1528_0_ - kinetics_479_0_ - mGluR_internalize_1559_0__Kf - mGluR_p_dot_barr2_1555_0_ + kinetics_451_0_ + mGluR_internalize_1532_0__Kf + mGluR_p_dot_barr2_1528_0_ - + - + 919.117647059 - -790.361445783 + 790.361445783 white 34 - + - - + + - kinetics_479_0_ * barr2_dissoc_1561_0__Kf * Internal_mGluR_p_dot_barr2_1547_0_ + kinetics_451_0_ * barr2_dissoc_1534_0__Kf * Internal_mGluR_p_dot_barr2_1520_0_ - kinetics_479_0_ - barr2_dissoc_1561_0__Kf - Internal_mGluR_p_dot_barr2_1547_0_ + kinetics_451_0_ + barr2_dissoc_1534_0__Kf + Internal_mGluR_p_dot_barr2_1520_0_ - + - + 933.823529412 - -790.361445783 + 790.361445783 white 34 - + - + - kinetics_479_0_ * mGluR_recycling_1563_0__Kf * Internal_mGluR_1551_0_ + kinetics_451_0_ * mGluR_recycling_1536_0__Kf * Internal_mGluR_1524_0_ - kinetics_479_0_ - mGluR_recycling_1563_0__Kf - Internal_mGluR_1551_0_ + kinetics_451_0_ + mGluR_recycling_1536_0__Kf + Internal_mGluR_1524_0_ - + - + Navarro DL et al., Amino Acids (2005). Kd for glutamte-mGluR for rat fetus is 599 (+/-) 89.7 nM and for mothers is 534.3 (+/-) 89.7 nM. Therefore, assuming Kd = 595nM @@ -8490,22 +8937,22 @@ 948.529411765 - -790.361445783 + 790.361445783 white 34 - + - - + + - kinetics_479_0_ * ligand_dissoc_1565_0__Kf * L_dot_mGluR_p_dot_barr2_1549_0_-kinetics_479_0_ * ligand_dissoc_1565_0__Kb * Glutamate_1089_0_*mGluR_p_dot_barr2_1555_0_ + kinetics_451_0_ * ligand_dissoc_1538_0__Kf * L_dot_mGluR_p_dot_barr2_1522_0_-kinetics_451_0_ * ligand_dissoc_1538_0__Kb * mGluR_p_dot_barr2_1528_0_*Glutamate_1062_0_ @@ -8513,26 +8960,26 @@ - kinetics_479_0_ - ligand_dissoc_1565_0__Kf - L_dot_mGluR_p_dot_barr2_1549_0_ + kinetics_451_0_ + ligand_dissoc_1538_0__Kf + L_dot_mGluR_p_dot_barr2_1522_0_ - kinetics_479_0_ - ligand_dissoc_1565_0__Kb - Glutamate_1089_0_ - mGluR_p_dot_barr2_1555_0_ + kinetics_451_0_ + ligand_dissoc_1538_0__Kb + mGluR_p_dot_barr2_1528_0_ + Glutamate_1062_0_ - - + + - + Rate consts from Chen et al Biochem 32, 1032 (1993) k3 = k2 = 4 k1 = 9e-5 recalculated gives 1.666e-5, which is not very different. Looks like k3 is rate-limiting in this case: there is a huge amount of craf locked up in the enz complex. Let us assume a 10x higher Km, ie, lower affinity. k1 drops by 10x. Also changed k2 to 4x k3. Lowerd k1 to 1e-6 to balance 10X DAG sensitivity of PKC @@ -8540,46 +8987,46 @@ - PKC_active_509_0_ - craf_1_668_0_ - PKC_act_raf_cplx_512_0_ - PKC_act_raf_511_0_ + PKC_active_482_0_ + craf_1_641_0_ + PKC_act_raf_cplx_485_0_ + PKC_act_raf_484_0_ 1 66.1764705882 - -125.301204819 + 125.301204819 yellow red - - + + - + - kinetics_479_0_ * ( k1 * craf_1_668_0_*PKC_active_509_0_ - k2 * PKC_act_raf_cplx_512_0_ ) + kinetics_451_0_ * ( k1 * craf_1_641_0_*PKC_active_482_0_ - k2 * PKC_act_raf_cplx_485_0_ ) - kinetics_479_0_ + kinetics_451_0_ k1 - craf_1_668_0_ - PKC_active_509_0_ + craf_1_641_0_ + PKC_active_482_0_ k2 - PKC_act_raf_cplx_512_0_ + PKC_act_raf_cplx_485_0_ @@ -8590,39 +9037,39 @@ - + - PKC_act_raf_cplx_512_0_ - PKC_active_509_0_ - craf_1_p_670_0_ - PKC_act_raf_511_0_ + PKC_act_raf_cplx_485_0_ + PKC_active_482_0_ + craf_1_p_643_0_ + PKC_act_raf_484_0_ 2 66.1764705882 - -125.301204819 + 125.301204819 yellow red - + - - + + - kinetics_479_0_ * k3*PKC_act_raf_cplx_512_0_ + kinetics_451_0_ * k3*PKC_act_raf_cplx_485_0_ - kinetics_479_0_ + kinetics_451_0_ k3 - PKC_act_raf_cplx_512_0_ + PKC_act_raf_cplx_485_0_ @@ -8630,7 +9077,7 @@ - + Rate consts copied from PCK-act-raf This reaction inactivates GAP. The idea is from the Boguski and McCormick review. @@ -8638,46 +9085,46 @@ - PKC_active_509_0_ - GAP_731_0_ - PKC_inact_GAP_cplx_515_0_ - PKC_inact_GAP_514_0_ + PKC_active_482_0_ + GAP_704_0_ + PKC_inact_GAP_cplx_488_0_ + PKC_inact_GAP_487_0_ 1 66.1764705882 - -115.662650602 + 115.662650602 yellow red - - + + - + - kinetics_479_0_ * ( k1 * GAP_731_0_*PKC_active_509_0_ - k2 * PKC_inact_GAP_cplx_515_0_ ) + kinetics_451_0_ * ( k1 * GAP_704_0_*PKC_active_482_0_ - k2 * PKC_inact_GAP_cplx_488_0_ ) - kinetics_479_0_ + kinetics_451_0_ k1 - GAP_731_0_ - PKC_active_509_0_ + GAP_704_0_ + PKC_active_482_0_ k2 - PKC_inact_GAP_cplx_515_0_ + PKC_inact_GAP_cplx_488_0_ @@ -8688,39 +9135,39 @@ - + - PKC_inact_GAP_cplx_515_0_ - PKC_active_509_0_ - GAP_p_729_0_ - PKC_inact_GAP_514_0_ + PKC_inact_GAP_cplx_488_0_ + PKC_active_482_0_ + GAP_p_702_0_ + PKC_inact_GAP_487_0_ 2 66.1764705882 - -115.662650602 + 115.662650602 yellow red - + - - + + - kinetics_479_0_ * k3*PKC_inact_GAP_cplx_515_0_ + kinetics_451_0_ * k3*PKC_inact_GAP_cplx_488_0_ - kinetics_479_0_ + kinetics_451_0_ k3 - PKC_inact_GAP_cplx_515_0_ + PKC_inact_GAP_cplx_488_0_ @@ -8728,7 +9175,7 @@ - + Rate consts from PKC-act-raf. This reaction activates GEF. It can lead to at least 2X stim of ras, and a 2X stim of MAPK over and above that obtained via direct phosph of c-raf. Note that it is a push-pull reaction, and there is also a contribution through the phosphorylation and inactivation of GAPs. The original PKC-act-raf rate consts are too fast. We lower K1 by 10 X @@ -8736,46 +9183,46 @@ - PKC_active_509_0_ - inact_GEF_715_0_ - PKC_act_GEF_cplx_518_0_ - PKC_act_GEF_517_0_ + PKC_active_482_0_ + inact_GEF_688_0_ + PKC_act_GEF_cplx_491_0_ + PKC_act_GEF_490_0_ 1 66.1764705882 - -106.024096386 + 106.024096386 yellow red - - + + - + - kinetics_479_0_ * ( k1 * inact_GEF_715_0_*PKC_active_509_0_ - k2 * PKC_act_GEF_cplx_518_0_ ) + kinetics_451_0_ * ( k1 * inact_GEF_688_0_*PKC_active_482_0_ - k2 * PKC_act_GEF_cplx_491_0_ ) - kinetics_479_0_ + kinetics_451_0_ k1 - inact_GEF_715_0_ - PKC_active_509_0_ + inact_GEF_688_0_ + PKC_active_482_0_ k2 - PKC_act_GEF_cplx_518_0_ + PKC_act_GEF_cplx_491_0_ @@ -8786,39 +9233,39 @@ - + - PKC_act_GEF_cplx_518_0_ - PKC_active_509_0_ - GEF_p_720_0_ - PKC_act_GEF_517_0_ + PKC_act_GEF_cplx_491_0_ + PKC_active_482_0_ + GEF_p_693_0_ + PKC_act_GEF_490_0_ 2 66.1764705882 - -106.024096386 + 106.024096386 yellow red - + - - + + - kinetics_479_0_ * k3*PKC_act_GEF_cplx_518_0_ + kinetics_451_0_ * k3*PKC_act_GEF_cplx_491_0_ - kinetics_479_0_ + kinetics_451_0_ k3 - PKC_act_GEF_cplx_518_0_ + PKC_act_GEF_cplx_491_0_ @@ -8826,7 +9273,7 @@ - + Rates from Huang et al ABB 305:2 570-580 1993 @@ -8834,46 +9281,46 @@ - PKC_active_509_0_ - neurogranin_885_0_ - PKC_phosph_neurogranin_cplx_521_0_ - PKC_phosph_neurogranin_520_0_ + PKC_active_482_0_ + neurogranin_858_0_ + PKC_phosph_neurogranin_cplx_494_0_ + PKC_phosph_neurogranin_493_0_ 1 66.1764705882 - -96.3855421687 + 96.3855421687 red red - - + + - + - kinetics_479_0_ * ( k1 * PKC_active_509_0_*neurogranin_885_0_ - k2 * PKC_phosph_neurogranin_cplx_521_0_ ) + kinetics_451_0_ * ( k1 * PKC_active_482_0_*neurogranin_858_0_ - k2 * PKC_phosph_neurogranin_cplx_494_0_ ) - kinetics_479_0_ + kinetics_451_0_ k1 - PKC_active_509_0_ - neurogranin_885_0_ + PKC_active_482_0_ + neurogranin_858_0_ k2 - PKC_phosph_neurogranin_cplx_521_0_ + PKC_phosph_neurogranin_cplx_494_0_ @@ -8884,39 +9331,39 @@ - + - PKC_phosph_neurogranin_cplx_521_0_ - PKC_active_509_0_ - neurogranin_p_883_0_ - PKC_phosph_neurogranin_520_0_ + PKC_phosph_neurogranin_cplx_494_0_ + PKC_active_482_0_ + neurogranin_p_856_0_ + PKC_phosph_neurogranin_493_0_ 2 66.1764705882 - -96.3855421687 + 96.3855421687 red red - + - - + + - kinetics_479_0_ * k3*PKC_phosph_neurogranin_cplx_521_0_ + kinetics_451_0_ * k3*PKC_phosph_neurogranin_cplx_494_0_ - kinetics_479_0_ + kinetics_451_0_ k3 - PKC_phosph_neurogranin_cplx_521_0_ + PKC_phosph_neurogranin_cplx_494_0_ @@ -8924,7 +9371,7 @@ - + Rates are 60% those of PKC-phosph-neurogranin. See Huang et al ABB 305:2 570-580 1993 @@ -8932,46 +9379,46 @@ - PKC_active_509_0_ - neurogranin_CaM_881_0_ - PKC_phosph_ng_CaM_cplx_524_0_ - PKC_phosph_ng_CaM_523_0_ + PKC_active_482_0_ + neurogranin_CaM_854_0_ + PKC_phosph_ng_CaM_cplx_497_0_ + PKC_phosph_ng_CaM_496_0_ 1 66.1764705882 - -86.7469879518 + 86.7469879518 red red - - + + - + - kinetics_479_0_ * ( k1 * neurogranin_CaM_881_0_*PKC_active_509_0_ - k2 * PKC_phosph_ng_CaM_cplx_524_0_ ) + kinetics_451_0_ * ( k1 * PKC_active_482_0_*neurogranin_CaM_854_0_ - k2 * PKC_phosph_ng_CaM_cplx_497_0_ ) - kinetics_479_0_ + kinetics_451_0_ k1 - neurogranin_CaM_881_0_ - PKC_active_509_0_ + PKC_active_482_0_ + neurogranin_CaM_854_0_ k2 - PKC_phosph_ng_CaM_cplx_524_0_ + PKC_phosph_ng_CaM_cplx_497_0_ @@ -8982,41 +9429,41 @@ - + - PKC_phosph_ng_CaM_cplx_524_0_ - PKC_active_509_0_ - neurogranin_p_883_0_ - CaM_879_0_ - PKC_phosph_ng_CaM_523_0_ + PKC_phosph_ng_CaM_cplx_497_0_ + PKC_active_482_0_ + neurogranin_p_856_0_ + CaM_852_0_ + PKC_phosph_ng_CaM_496_0_ 2 66.1764705882 - -86.7469879518 + 86.7469879518 red red - + - - - + + + - kinetics_479_0_ * k3*PKC_phosph_ng_CaM_cplx_524_0_ + kinetics_451_0_ * k3*PKC_phosph_ng_CaM_cplx_497_0_ - kinetics_479_0_ + kinetics_451_0_ k3 - PKC_phosph_ng_CaM_cplx_524_0_ + PKC_phosph_ng_CaM_cplx_497_0_ @@ -9024,7 +9471,7 @@ - + Phorbol esters have little effect on AC1 or on the Gs-stimulation of AC2. So in this model we are only dealing with the increase in basal activation of AC2 induced by PKC k1 = 1.66e-6 k2 = 16 k3 =4 @@ -9032,46 +9479,46 @@ - PKC_active_509_0_ - AC2_1041_0_ - phosph_AC2_cplx_527_0_ - phosph_AC2_526_0_ + PKC_active_482_0_ + AC2_1014_0_ + phosph_AC2_cplx_500_0_ + phosph_AC2_499_0_ 1 66.1764705882 - -77.1084337349 + 77.1084337349 red red - - + + - + - kinetics_479_0_ * ( k1 * AC2_1041_0_*PKC_active_509_0_ - k2 * phosph_AC2_cplx_527_0_ ) + kinetics_451_0_ * ( k1 * PKC_active_482_0_*AC2_1014_0_ - k2 * phosph_AC2_cplx_500_0_ ) - kinetics_479_0_ + kinetics_451_0_ k1 - AC2_1041_0_ - PKC_active_509_0_ + PKC_active_482_0_ + AC2_1014_0_ k2 - phosph_AC2_cplx_527_0_ + phosph_AC2_cplx_500_0_ @@ -9082,39 +9529,39 @@ - + - phosph_AC2_cplx_527_0_ - PKC_active_509_0_ - AC2_p_1033_0_ - phosph_AC2_526_0_ + phosph_AC2_cplx_500_0_ + PKC_active_482_0_ + AC2_p_1006_0_ + phosph_AC2_499_0_ 2 66.1764705882 - -77.1084337349 + 77.1084337349 red red - + - - + + - kinetics_479_0_ * k3*phosph_AC2_cplx_527_0_ + kinetics_451_0_ * k3*phosph_AC2_cplx_500_0_ - kinetics_479_0_ + kinetics_451_0_ k3 - phosph_AC2_cplx_527_0_ + phosph_AC2_cplx_500_0_ @@ -9122,7 +9569,7 @@ - + 10 x raise oct22 12 x oct 24, set k2 = 4 * k3 @@ -9130,46 +9577,46 @@ - PLA2_Ca_p_553_0_ - APC_573_0_ - kenz_cplx_556_0_ - kenz_555_0_ + PLA2_Ca_p_526_0_ + APC_546_0_ + kenz_cplx_529_0_ + kenz_528_0_ 1 161.764705882 - -19.2771084337 + 19.2771084337 yellow red - - + + - + - kinetics_479_0_ * ( k1 * PLA2_Ca_p_553_0_*APC_573_0_ - k2 * kenz_cplx_556_0_ ) + kinetics_451_0_ * ( k1 * APC_546_0_*PLA2_Ca_p_526_0_ - k2 * kenz_cplx_529_0_ ) - kinetics_479_0_ + kinetics_451_0_ k1 - PLA2_Ca_p_553_0_ - APC_573_0_ + APC_546_0_ + PLA2_Ca_p_526_0_ k2 - kenz_cplx_556_0_ + kenz_cplx_529_0_ @@ -9180,39 +9627,39 @@ - + - kenz_cplx_556_0_ - PLA2_Ca_p_553_0_ - Arachidonic_Acid_596_0_ - kenz_555_0_ + kenz_cplx_529_0_ + PLA2_Ca_p_526_0_ + Arachidonic_Acid_569_0_ + kenz_528_0_ 2 161.764705882 - -19.2771084337 + 19.2771084337 yellow red - + - - + + - kinetics_479_0_ * k3*kenz_cplx_556_0_ + kinetics_451_0_ * k3*kenz_cplx_529_0_ - kinetics_479_0_ + kinetics_451_0_ k3 - kenz_cplx_556_0_ + kenz_cplx_529_0_ @@ -9220,7 +9667,7 @@ - + 10 X raise oct 22 12 X further raise oct 24 to allow for correct conc of enzyme @@ -9228,46 +9675,46 @@ - PIP2_PLA2_p_558_0_ - APC_573_0_ - kenz_cplx_561_0_ - kenz_560_0_ + PIP2_PLA2_p_531_0_ + APC_546_0_ + kenz_cplx_534_0_ + kenz_533_0_ 1 176.470588235 - -19.2771084337 + 19.2771084337 cyan red - - + + - + - kinetics_479_0_ * ( k1 * APC_573_0_*PIP2_PLA2_p_558_0_ - k2 * kenz_cplx_561_0_ ) + kinetics_451_0_ * ( k1 * APC_546_0_*PIP2_PLA2_p_531_0_ - k2 * kenz_cplx_534_0_ ) - kinetics_479_0_ + kinetics_451_0_ k1 - APC_573_0_ - PIP2_PLA2_p_558_0_ + APC_546_0_ + PIP2_PLA2_p_531_0_ k2 - kenz_cplx_561_0_ + kenz_cplx_534_0_ @@ -9278,39 +9725,39 @@ - + - kenz_cplx_561_0_ - PIP2_PLA2_p_558_0_ - Arachidonic_Acid_596_0_ - kenz_560_0_ + kenz_cplx_534_0_ + PIP2_PLA2_p_531_0_ + Arachidonic_Acid_569_0_ + kenz_533_0_ 2 176.470588235 - -19.2771084337 + 19.2771084337 cyan red - + - - + + - kinetics_479_0_ * k3*kenz_cplx_561_0_ + kinetics_451_0_ * k3*kenz_cplx_534_0_ - kinetics_479_0_ + kinetics_451_0_ k3 - kenz_cplx_561_0_ + kenz_cplx_534_0_ @@ -9318,7 +9765,7 @@ - + 10 x raise oct 22 12 x and rescale for k2 = 4 * k3 convention oct 24 Increase further to get the match to expt, which was spoilt due to large accumulation of PLA2 in the enzyme complexed forms. Lets raise k3, leaving the others at k1 = 1.5e-5 and k2 = 144 since they are large already. @@ -9326,46 +9773,46 @@ - PIP2_Ca_PLA2_p_563_0_ - APC_573_0_ - kenz_cplx_566_0_ - kenz_565_0_ + PIP2_Ca_PLA2_p_536_0_ + APC_546_0_ + kenz_cplx_539_0_ + kenz_538_0_ 1 191.176470588 - -19.2771084337 + 19.2771084337 cyan red - - + + - + - kinetics_479_0_ * ( k1 * PIP2_Ca_PLA2_p_563_0_*APC_573_0_ - k2 * kenz_cplx_566_0_ ) + kinetics_451_0_ * ( k1 * PIP2_Ca_PLA2_p_536_0_*APC_546_0_ - k2 * kenz_cplx_539_0_ ) - kinetics_479_0_ + kinetics_451_0_ k1 - PIP2_Ca_PLA2_p_563_0_ - APC_573_0_ + PIP2_Ca_PLA2_p_536_0_ + APC_546_0_ k2 - kenz_cplx_566_0_ + kenz_cplx_539_0_ @@ -9376,39 +9823,39 @@ - + - kenz_cplx_566_0_ - PIP2_Ca_PLA2_p_563_0_ - Arachidonic_Acid_596_0_ - kenz_565_0_ + kenz_cplx_539_0_ + PIP2_Ca_PLA2_p_536_0_ + Arachidonic_Acid_569_0_ + kenz_538_0_ 2 191.176470588 - -19.2771084337 + 19.2771084337 cyan red - + - - + + - kinetics_479_0_ * k3*kenz_cplx_566_0_ + kinetics_451_0_ * k3*kenz_cplx_539_0_ - kinetics_479_0_ + kinetics_451_0_ k3 - kenz_cplx_566_0_ + kenz_cplx_539_0_ @@ -9416,7 +9863,7 @@ - + 10 X raise oct 22 12 X raise oct 24 + conversion to k2 =4 * k3 @@ -9424,46 +9871,46 @@ - DAG_Ca_PLA2_p_568_0_ - APC_573_0_ - kenz_cplx_571_0_ - kenz_570_0_ + DAG_Ca_PLA2_p_541_0_ + APC_546_0_ + kenz_cplx_544_0_ + kenz_543_0_ 1 205.882352941 - -19.2771084337 + 19.2771084337 pink red - - + + - + - kinetics_479_0_ * ( k1 * DAG_Ca_PLA2_p_568_0_*APC_573_0_ - k2 * kenz_cplx_571_0_ ) + kinetics_451_0_ * ( k1 * APC_546_0_*DAG_Ca_PLA2_p_541_0_ - k2 * kenz_cplx_544_0_ ) - kinetics_479_0_ + kinetics_451_0_ k1 - DAG_Ca_PLA2_p_568_0_ - APC_573_0_ + APC_546_0_ + DAG_Ca_PLA2_p_541_0_ k2 - kenz_cplx_571_0_ + kenz_cplx_544_0_ @@ -9474,39 +9921,39 @@ - + - kenz_cplx_571_0_ - DAG_Ca_PLA2_p_568_0_ - Arachidonic_Acid_596_0_ - kenz_570_0_ + kenz_cplx_544_0_ + DAG_Ca_PLA2_p_541_0_ + Arachidonic_Acid_569_0_ + kenz_543_0_ 2 205.882352941 - -19.2771084337 + 19.2771084337 pink red - + - - + + - kinetics_479_0_ * k3*kenz_cplx_571_0_ + kinetics_451_0_ * k3*kenz_cplx_544_0_ - kinetics_479_0_ + kinetics_451_0_ k3 - kenz_cplx_571_0_ + kenz_cplx_544_0_ @@ -9514,7 +9961,7 @@ - + This form should be 3 to 6 times as fast as the Ca-only form. I have scaled by 4x which seems to give a 5x rise. 10x raise Oct 22 12 x oct 24, changed k2 = 4 * k3 @@ -9522,46 +9969,46 @@ - PLA2_p_Ca_575_0_ - APC_573_0_ - kenz_cplx_578_0_ - kenz_577_0_ + PLA2_p_Ca_548_0_ + APC_546_0_ + kenz_cplx_551_0_ + kenz_550_0_ 1 235.294117647 - -19.2771084337 + 19.2771084337 orange red - - + + - + - kinetics_479_0_ * ( k1 * APC_573_0_*PLA2_p_Ca_575_0_ - k2 * kenz_cplx_578_0_ ) + kinetics_451_0_ * ( k1 * APC_546_0_*PLA2_p_Ca_548_0_ - k2 * kenz_cplx_551_0_ ) - kinetics_479_0_ + kinetics_451_0_ k1 - APC_573_0_ - PLA2_p_Ca_575_0_ + APC_546_0_ + PLA2_p_Ca_548_0_ k2 - kenz_cplx_578_0_ + kenz_cplx_551_0_ @@ -9572,39 +10019,39 @@ - + - kenz_cplx_578_0_ - PLA2_p_Ca_575_0_ - Arachidonic_Acid_596_0_ - kenz_577_0_ + kenz_cplx_551_0_ + PLA2_p_Ca_548_0_ + Arachidonic_Acid_569_0_ + kenz_550_0_ 2 235.294117647 - -19.2771084337 + 19.2771084337 orange red - + - - + + - kinetics_479_0_ * k3*kenz_cplx_578_0_ + kinetics_451_0_ * k3*kenz_cplx_551_0_ - kinetics_479_0_ + kinetics_451_0_ k3 - kenz_cplx_578_0_ + kenz_cplx_551_0_ @@ -9612,7 +10059,7 @@ - + From Sternweis et al Phil Trans R Soc Lond 1992, also matched by Homma et al. k1 = 1.5e-5, now 4.2e-6 k2 = 70/sec; now 40/sec k3 = 17.5/sec; now 10/sec Note that the wording in Sternweis et al is ambiguous re the Km. @@ -9620,46 +10067,46 @@ - PLC_Ca_604_0_ - PIP2_636_0_ - PLC_Ca_cplx_607_0_ - PLC_Ca_606_0_ + PLC_Ca_577_0_ + PIP2_609_0_ + PLC_Ca_cplx_580_0_ + PLC_Ca_579_0_ 1 323.529411765 - -19.2771084337 + 19.2771084337 cyan red - - + + - + - kinetics_479_0_ * ( k1 * PIP2_636_0_*PLC_Ca_604_0_ - k2 * PLC_Ca_cplx_607_0_ ) + kinetics_451_0_ * ( k1 * PLC_Ca_577_0_*PIP2_609_0_ - k2 * PLC_Ca_cplx_580_0_ ) - kinetics_479_0_ + kinetics_451_0_ k1 - PIP2_636_0_ - PLC_Ca_604_0_ + PLC_Ca_577_0_ + PIP2_609_0_ k2 - PLC_Ca_cplx_607_0_ + PLC_Ca_cplx_580_0_ @@ -9670,41 +10117,41 @@ - + - PLC_Ca_cplx_607_0_ - PLC_Ca_604_0_ - DAG_632_0_ - IP3_634_0_ - PLC_Ca_606_0_ + PLC_Ca_cplx_580_0_ + PLC_Ca_577_0_ + DAG_605_0_ + IP3_607_0_ + PLC_Ca_579_0_ 2 323.529411765 - -19.2771084337 + 19.2771084337 cyan red - + - - - + + + - kinetics_479_0_ * k3*PLC_Ca_cplx_607_0_ + kinetics_451_0_ * k3*PLC_Ca_cplx_580_0_ - kinetics_479_0_ + kinetics_451_0_ k3 - PLC_Ca_cplx_607_0_ + PLC_Ca_cplx_580_0_ @@ -9712,7 +10159,7 @@ - + From Sternweis et al, Phil Trans R Soc Lond 1992, and the values from other refs eg Homma et al JBC 263(14) pp6592 1988 match. k1 = 5e-5/sec k2 = 240/sec; now 120/sec k3 = 60/sec; now 30/sec Note that the wording in Sternweis et al is ambiguous wr. to the Km for Gq vs non-Gq states of PLC. K1 is still a bit too low. Raise to 7e-5 9 Jun 1996: k1 was 0.0002, changed to 5e-5 @@ -9720,46 +10167,46 @@ - PLC_Ca_Gq_609_0_ - PIP2_636_0_ - PLCb_Ca_Gq_cplx_612_0_ - PLCb_Ca_Gq_611_0_ + PLC_Ca_Gq_582_0_ + PIP2_609_0_ + PLCb_Ca_Gq_cplx_585_0_ + PLCb_Ca_Gq_584_0_ 1 338.235294118 - -19.2771084337 + 19.2771084337 cyan red - - + + - + - kinetics_479_0_ * ( k1 * PLC_Ca_Gq_609_0_*PIP2_636_0_ - k2 * PLCb_Ca_Gq_cplx_612_0_ ) + kinetics_451_0_ * ( k1 * PIP2_609_0_*PLC_Ca_Gq_582_0_ - k2 * PLCb_Ca_Gq_cplx_585_0_ ) - kinetics_479_0_ + kinetics_451_0_ k1 - PLC_Ca_Gq_609_0_ - PIP2_636_0_ + PIP2_609_0_ + PLC_Ca_Gq_582_0_ k2 - PLCb_Ca_Gq_cplx_612_0_ + PLCb_Ca_Gq_cplx_585_0_ @@ -9770,41 +10217,41 @@ - + - PLCb_Ca_Gq_cplx_612_0_ - PLC_Ca_Gq_609_0_ - DAG_632_0_ - IP3_634_0_ - PLCb_Ca_Gq_611_0_ + PLCb_Ca_Gq_cplx_585_0_ + PLC_Ca_Gq_582_0_ + DAG_605_0_ + IP3_607_0_ + PLCb_Ca_Gq_584_0_ 2 338.235294118 - -19.2771084337 + 19.2771084337 cyan red - + - - - + + + - kinetics_479_0_ * k3*PLCb_Ca_Gq_cplx_612_0_ + kinetics_451_0_ * k3*PLCb_Ca_Gq_cplx_585_0_ - kinetics_479_0_ + kinetics_451_0_ k3 - PLCb_Ca_Gq_cplx_612_0_ + PLCb_Ca_Gq_cplx_585_0_ @@ -9812,7 +10259,7 @@ - + Km = 25uM @ 50 uM ATP and 1mg/ml MBP (huge XS of substrate) Vmax = 4124 pmol/min/ml at a conc of 125 pmol/ml of enz, so: k3 = .5/sec (rate limiting) k1 = (k2 + k3)/Km = (.5 + 0)/(25*6e5) = 2e-8 (#/cell)^-1 #s from Sanghera et al JBC 265 pp 52 , 1990. From Nemenoff et al JBC 268(3):1960-1964 - using Sanghera's 1e-4 ratio of MAPK to protein, we get k3 = 7/sec from 1000 pmol/min/mg fig 5 @@ -9820,46 +10267,46 @@ - MAPK_p_p_648_0_ - PLA2_cytosolic_551_0_ - MAPK_p_p_cplx_651_0_ - MAPK_p_p_650_0_ + MAPK_p_p_621_0_ + PLA2_cytosolic_524_0_ + MAPK_p_p_cplx_624_0_ + MAPK_p_p_623_0_ 1 588.235294118 - -19.2771084337 + 19.2771084337 orange red - - + + - + - kinetics_479_0_ * ( k1 * MAPK_p_p_648_0_*PLA2_cytosolic_551_0_ - k2 * MAPK_p_p_cplx_651_0_ ) + kinetics_451_0_ * ( k1 * PLA2_cytosolic_524_0_*MAPK_p_p_621_0_ - k2 * MAPK_p_p_cplx_624_0_ ) - kinetics_479_0_ + kinetics_451_0_ k1 - MAPK_p_p_648_0_ - PLA2_cytosolic_551_0_ + PLA2_cytosolic_524_0_ + MAPK_p_p_621_0_ k2 - MAPK_p_p_cplx_651_0_ + MAPK_p_p_cplx_624_0_ @@ -9870,39 +10317,39 @@ - + - MAPK_p_p_cplx_651_0_ - MAPK_p_p_648_0_ - PLA2_p_580_0_ - MAPK_p_p_650_0_ + MAPK_p_p_cplx_624_0_ + MAPK_p_p_621_0_ + PLA2_p_553_0_ + MAPK_p_p_623_0_ 2 588.235294118 - -19.2771084337 + 19.2771084337 orange red - + - - + + - kinetics_479_0_ * k3*MAPK_p_p_cplx_651_0_ + kinetics_451_0_ * k3*MAPK_p_p_cplx_624_0_ - kinetics_479_0_ + kinetics_451_0_ k3 - MAPK_p_p_cplx_651_0_ + MAPK_p_p_cplx_624_0_ @@ -9910,7 +10357,7 @@ - + Ueki et al JBC 269(22):15756-15761 show the presence of this step, but not the rate consts, which are derived from Sanghera et al JBC 265(1):52-57, 1990, see the deriv in the MAPK* notes. @@ -9918,46 +10365,46 @@ - MAPK_p_p_648_0_ - craf_1_p_670_0_ - MAPK_p_p_feedback_cplx_654_0_ - MAPK_p_p_feedback_653_0_ + MAPK_p_p_621_0_ + craf_1_p_643_0_ + MAPK_p_p_feedback_cplx_627_0_ + MAPK_p_p_feedback_626_0_ 1 588.235294118 - -28.9156626506 + 28.9156626506 orange red - - + + - + - kinetics_479_0_ * ( k1 * MAPK_p_p_648_0_*craf_1_p_670_0_ - k2 * MAPK_p_p_feedback_cplx_654_0_ ) + kinetics_451_0_ * ( k1 * craf_1_p_643_0_*MAPK_p_p_621_0_ - k2 * MAPK_p_p_feedback_cplx_627_0_ ) - kinetics_479_0_ + kinetics_451_0_ k1 - MAPK_p_p_648_0_ - craf_1_p_670_0_ + craf_1_p_643_0_ + MAPK_p_p_621_0_ k2 - MAPK_p_p_feedback_cplx_654_0_ + MAPK_p_p_feedback_cplx_627_0_ @@ -9968,39 +10415,39 @@ - + - MAPK_p_p_feedback_cplx_654_0_ - MAPK_p_p_648_0_ - craf_1_p_p_682_0_ - MAPK_p_p_feedback_653_0_ + MAPK_p_p_feedback_cplx_627_0_ + MAPK_p_p_621_0_ + craf_1_p_p_655_0_ + MAPK_p_p_feedback_626_0_ 2 588.235294118 - -28.9156626506 + 28.9156626506 orange red - + - - + + - kinetics_479_0_ * k3*MAPK_p_p_feedback_cplx_654_0_ + kinetics_451_0_ * k3*MAPK_p_p_feedback_cplx_627_0_ - kinetics_479_0_ + kinetics_451_0_ k3 - MAPK_p_p_feedback_cplx_654_0_ + MAPK_p_p_feedback_cplx_627_0_ @@ -10008,7 +10455,7 @@ - + See Porfiri and McCormick JBC 271:10 pp5871 1996 for the existence of this step. We'll take the rates from the ones used for the phosph of Raf by MAPK. Sep 17 1997: The transient activation curve matches better with k1 up by 10 x. @@ -10016,46 +10463,46 @@ - MAPK_p_p_648_0_ - Sos_796_0_ - phosph_Sos_cplx_657_0_ - phosph_Sos_656_0_ + MAPK_p_p_621_0_ + Sos_769_0_ + phosph_Sos_cplx_630_0_ + phosph_Sos_629_0_ 1 588.235294118 - -38.5542168675 + 38.5542168675 orange red - - + + - + - kinetics_479_0_ * ( k1 * MAPK_p_p_648_0_*Sos_796_0_ - k2 * phosph_Sos_cplx_657_0_ ) + kinetics_451_0_ * ( k1 * Sos_769_0_*MAPK_p_p_621_0_ - k2 * phosph_Sos_cplx_630_0_ ) - kinetics_479_0_ + kinetics_451_0_ k1 - MAPK_p_p_648_0_ - Sos_796_0_ + Sos_769_0_ + MAPK_p_p_621_0_ k2 - phosph_Sos_cplx_657_0_ + phosph_Sos_cplx_630_0_ @@ -10066,39 +10513,39 @@ - + - phosph_Sos_cplx_657_0_ - MAPK_p_p_648_0_ - Sos_p_794_0_ - phosph_Sos_656_0_ + phosph_Sos_cplx_630_0_ + MAPK_p_p_621_0_ + Sos_p_767_0_ + phosph_Sos_629_0_ 2 588.235294118 - -38.5542168675 + 38.5542168675 orange red - + - - + + - kinetics_479_0_ * k3*phosph_Sos_cplx_657_0_ + kinetics_451_0_ * k3*phosph_Sos_cplx_630_0_ - kinetics_479_0_ + kinetics_451_0_ k3 - phosph_Sos_cplx_657_0_ + phosph_Sos_cplx_630_0_ @@ -10106,49 +10553,49 @@ - + - MAPK_p_p_648_0_ - S6K_1329_0_ - cluster_phospho_S6K_cplx_660_0_ - cluster_phospho_S6K_659_0_ + MAPK_p_p_621_0_ + S6K_1302_0_ + cluster_phospho_S6K_cplx_633_0_ + cluster_phospho_S6K_632_0_ 1 588.235294118 - -48.1927710843 + 48.1927710843 red red - - + + - + - kinetics_479_0_ * ( k1 * MAPK_p_p_648_0_*S6K_1329_0_ - k2 * cluster_phospho_S6K_cplx_660_0_ ) + kinetics_451_0_ * ( k1 * MAPK_p_p_621_0_*S6K_1302_0_ - k2 * cluster_phospho_S6K_cplx_633_0_ ) - kinetics_479_0_ + kinetics_451_0_ k1 - MAPK_p_p_648_0_ - S6K_1329_0_ + MAPK_p_p_621_0_ + S6K_1302_0_ k2 - cluster_phospho_S6K_cplx_660_0_ + cluster_phospho_S6K_cplx_633_0_ @@ -10159,39 +10606,39 @@ - + - cluster_phospho_S6K_cplx_660_0_ - MAPK_p_p_648_0_ - S6K_p_1327_0_ - cluster_phospho_S6K_659_0_ + cluster_phospho_S6K_cplx_633_0_ + MAPK_p_p_621_0_ + S6K_p_1300_0_ + cluster_phospho_S6K_632_0_ 2 588.235294118 - -48.1927710843 + 48.1927710843 red red - + - - + + - kinetics_479_0_ * k3*cluster_phospho_S6K_cplx_660_0_ + kinetics_451_0_ * k3*cluster_phospho_S6K_cplx_633_0_ - kinetics_479_0_ + kinetics_451_0_ k3 - cluster_phospho_S6K_cplx_660_0_ + cluster_phospho_S6K_cplx_633_0_ @@ -10199,49 +10646,49 @@ - + - MAPK_p_p_648_0_ - _4E_BP_t37_46_1365_0_ - MAPK_4E_BP_p_p_cplx_663_0_ - MAPK_4E_BP_p_p_662_0_ + MAPK_p_p_621_0_ + _4E_BP_t37_46_1338_0_ + MAPK_4E_BP_p_p_cplx_636_0_ + MAPK_4E_BP_p_p_635_0_ 1 588.235294118 - -57.8313253012 + 57.8313253012 red orange - - + + - + - kinetics_479_0_ * ( k1 * MAPK_p_p_648_0_*_4E_BP_t37_46_1365_0_ - k2 * MAPK_4E_BP_p_p_cplx_663_0_ ) + kinetics_451_0_ * ( k1 * _4E_BP_t37_46_1338_0_*MAPK_p_p_621_0_ - k2 * MAPK_4E_BP_p_p_cplx_636_0_ ) - kinetics_479_0_ + kinetics_451_0_ k1 - MAPK_p_p_648_0_ - _4E_BP_t37_46_1365_0_ + _4E_BP_t37_46_1338_0_ + MAPK_p_p_621_0_ k2 - MAPK_4E_BP_p_p_cplx_663_0_ + MAPK_4E_BP_p_p_cplx_636_0_ @@ -10252,39 +10699,39 @@ - + - MAPK_4E_BP_p_p_cplx_663_0_ - MAPK_p_p_648_0_ - _4E_BP_t37_46_s65_1357_0_ - MAPK_4E_BP_p_p_662_0_ + MAPK_4E_BP_p_p_cplx_636_0_ + MAPK_p_p_621_0_ + _4E_BP_t37_46_s65_1330_0_ + MAPK_4E_BP_p_p_635_0_ 2 588.235294118 - -57.8313253012 + 57.8313253012 red orange - + - - + + - kinetics_479_0_ * k3*MAPK_4E_BP_p_p_cplx_663_0_ + kinetics_451_0_ * k3*MAPK_4E_BP_p_p_cplx_636_0_ - kinetics_479_0_ + kinetics_451_0_ k3 - MAPK_4E_BP_p_p_cplx_663_0_ + MAPK_4E_BP_p_p_cplx_636_0_ @@ -10292,49 +10739,49 @@ - + - MAPK_p_p_648_0_ - eIF4E_BP_thr37_46_1361_0_ - MAPK_4E_BP_phospho_cplx_666_0_ - MAPK_4E_BP_phospho_665_0_ + MAPK_p_p_621_0_ + eIF4E_BP_thr37_46_1334_0_ + MAPK_4E_BP_phospho_cplx_639_0_ + MAPK_4E_BP_phospho_638_0_ 1 588.235294118 - -67.4698795181 + 67.4698795181 red 47 - - + + - + - kinetics_479_0_ * ( k1 * MAPK_p_p_648_0_*eIF4E_BP_thr37_46_1361_0_ - k2 * MAPK_4E_BP_phospho_cplx_666_0_ ) + kinetics_451_0_ * ( k1 * MAPK_p_p_621_0_*eIF4E_BP_thr37_46_1334_0_ - k2 * MAPK_4E_BP_phospho_cplx_639_0_ ) - kinetics_479_0_ + kinetics_451_0_ k1 - MAPK_p_p_648_0_ - eIF4E_BP_thr37_46_1361_0_ + MAPK_p_p_621_0_ + eIF4E_BP_thr37_46_1334_0_ k2 - MAPK_4E_BP_phospho_cplx_666_0_ + MAPK_4E_BP_phospho_cplx_639_0_ @@ -10345,39 +10792,39 @@ - + - MAPK_4E_BP_phospho_cplx_666_0_ - MAPK_p_p_648_0_ - eIF4E_BP_t37_46_s65_1363_0_ - MAPK_4E_BP_phospho_665_0_ + MAPK_4E_BP_phospho_cplx_639_0_ + MAPK_p_p_621_0_ + eIF4E_BP_t37_46_s65_1336_0_ + MAPK_4E_BP_phospho_638_0_ 2 588.235294118 - -67.4698795181 + 67.4698795181 red 47 - + - - + + - kinetics_479_0_ * k3*MAPK_4E_BP_phospho_cplx_666_0_ + kinetics_451_0_ * k3*MAPK_4E_BP_phospho_cplx_639_0_ - kinetics_479_0_ + kinetics_451_0_ k3 - MAPK_4E_BP_phospho_cplx_666_0_ + MAPK_4E_BP_phospho_cplx_639_0_ @@ -10385,49 +10832,49 @@ - + - craf_1_p_670_0_ - MAPKK_678_0_ - MEK_phospho_cplx_673_0_ - MEK_phospho_672_0_ + craf_1_p_643_0_ + MAPKK_651_0_ + MEK_phospho_cplx_646_0_ + MEK_phospho_645_0_ 1 617.647058824 - -19.2771084337 + 19.2771084337 0 black - - + + - + - kinetics_479_0_ * ( k1 * MAPKK_678_0_*craf_1_p_670_0_ - k2 * MEK_phospho_cplx_673_0_ ) + kinetics_451_0_ * ( k1 * craf_1_p_643_0_*MAPKK_651_0_ - k2 * MEK_phospho_cplx_646_0_ ) - kinetics_479_0_ + kinetics_451_0_ k1 - MAPKK_678_0_ - craf_1_p_670_0_ + craf_1_p_643_0_ + MAPKK_651_0_ k2 - MEK_phospho_cplx_673_0_ + MEK_phospho_cplx_646_0_ @@ -10438,39 +10885,39 @@ - + - MEK_phospho_cplx_673_0_ - craf_1_p_670_0_ - MAPKK_p_694_0_ - MEK_phospho_672_0_ + MEK_phospho_cplx_646_0_ + craf_1_p_643_0_ + MAPKK_p_667_0_ + MEK_phospho_645_0_ 2 617.647058824 - -19.2771084337 + 19.2771084337 0 black - + - - + + - kinetics_479_0_ * k3*MEK_phospho_cplx_673_0_ + kinetics_451_0_ * k3*MEK_phospho_cplx_646_0_ - kinetics_479_0_ + kinetics_451_0_ k3 - MEK_phospho_cplx_673_0_ + MEK_phospho_cplx_646_0_ @@ -10478,49 +10925,49 @@ - + - craf_1_p_670_0_ - MAPKK_p_694_0_ - MEKp_phospho_cplx_676_0_ - MEKp_phospho_675_0_ + craf_1_p_643_0_ + MAPKK_p_667_0_ + MEKp_phospho_cplx_649_0_ + MEKp_phospho_648_0_ 1 617.647058824 - -28.9156626506 + 28.9156626506 63 black - - + + - + - kinetics_479_0_ * ( k1 * MAPKK_p_694_0_*craf_1_p_670_0_ - k2 * MEKp_phospho_cplx_676_0_ ) + kinetics_451_0_ * ( k1 * craf_1_p_643_0_*MAPKK_p_667_0_ - k2 * MEKp_phospho_cplx_649_0_ ) - kinetics_479_0_ + kinetics_451_0_ k1 - MAPKK_p_694_0_ - craf_1_p_670_0_ + craf_1_p_643_0_ + MAPKK_p_667_0_ k2 - MEKp_phospho_cplx_676_0_ + MEKp_phospho_cplx_649_0_ @@ -10531,39 +10978,39 @@ - + - MEKp_phospho_cplx_676_0_ - craf_1_p_670_0_ - MAPKK_p_p_686_0_ - MEKp_phospho_675_0_ + MEKp_phospho_cplx_649_0_ + craf_1_p_643_0_ + MAPKK_p_p_659_0_ + MEKp_phospho_648_0_ 2 617.647058824 - -28.9156626506 + 28.9156626506 63 black - + - - + + - kinetics_479_0_ * k3*MEKp_phospho_cplx_676_0_ + kinetics_451_0_ * k3*MEKp_phospho_cplx_649_0_ - kinetics_479_0_ + kinetics_451_0_ k3 - MEKp_phospho_cplx_676_0_ + MEKp_phospho_cplx_649_0_ @@ -10571,7 +11018,7 @@ - + The actual MAPKK is 2 forms from Seger et al JBC 267:20 14373(1992) Vmax = 150nmol/min/mg From Haystead et al FEBS 306(1):17-22 we get Km=46.6nM for at least one of the phosphs. Putting these together: k3=0.15/sec, scale to get k2=0.6. k1=0.75/46.6nM=2.7e-5 @@ -10579,46 +11026,46 @@ - MAPKK_p_p_686_0_ - MAPK_680_0_ - MAPKKtyr_cplx_689_0_ - MAPKKtyr_688_0_ + MAPKK_p_p_659_0_ + MAPK_653_0_ + MAPKKtyr_cplx_662_0_ + MAPKKtyr_661_0_ 1 691.176470588 - -19.2771084337 + 19.2771084337 pink red - - + + - + - kinetics_479_0_ * ( k1 * MAPK_680_0_*MAPKK_p_p_686_0_ - k2 * MAPKKtyr_cplx_689_0_ ) + kinetics_451_0_ * ( k1 * MAPKK_p_p_659_0_*MAPK_653_0_ - k2 * MAPKKtyr_cplx_662_0_ ) - kinetics_479_0_ + kinetics_451_0_ k1 - MAPK_680_0_ - MAPKK_p_p_686_0_ + MAPKK_p_p_659_0_ + MAPK_653_0_ k2 - MAPKKtyr_cplx_689_0_ + MAPKKtyr_cplx_662_0_ @@ -10629,39 +11076,39 @@ - + - MAPKKtyr_cplx_689_0_ - MAPKK_p_p_686_0_ - MAPK_p_684_0_ - MAPKKtyr_688_0_ + MAPKKtyr_cplx_662_0_ + MAPKK_p_p_659_0_ + MAPK_p_657_0_ + MAPKKtyr_661_0_ 2 691.176470588 - -19.2771084337 + 19.2771084337 pink red - + - - + + - kinetics_479_0_ * k3*MAPKKtyr_cplx_689_0_ + kinetics_451_0_ * k3*MAPKKtyr_cplx_662_0_ - kinetics_479_0_ + kinetics_451_0_ k3 - MAPKKtyr_cplx_689_0_ + MAPKKtyr_cplx_662_0_ @@ -10669,7 +11116,7 @@ - + Rate consts same as for MAPKKtyr. @@ -10677,46 +11124,46 @@ - MAPKK_p_p_686_0_ - MAPK_p_684_0_ - MAPKKthr_cplx_692_0_ - MAPKKthr_691_0_ + MAPKK_p_p_659_0_ + MAPK_p_657_0_ + MAPKKthr_cplx_665_0_ + MAPKKthr_664_0_ 1 691.176470588 - -28.9156626506 + 28.9156626506 pink red - - + + - + - kinetics_479_0_ * ( k1 * MAPK_p_684_0_*MAPKK_p_p_686_0_ - k2 * MAPKKthr_cplx_692_0_ ) + kinetics_451_0_ * ( k1 * MAPK_p_657_0_*MAPKK_p_p_659_0_ - k2 * MAPKKthr_cplx_665_0_ ) - kinetics_479_0_ + kinetics_451_0_ k1 - MAPK_p_684_0_ - MAPKK_p_p_686_0_ + MAPK_p_657_0_ + MAPKK_p_p_659_0_ k2 - MAPKKthr_cplx_692_0_ + MAPKKthr_cplx_665_0_ @@ -10727,39 +11174,39 @@ - + - MAPKKthr_cplx_692_0_ - MAPKK_p_p_686_0_ - MAPK_p_p_648_0_ - MAPKKthr_691_0_ + MAPKKthr_cplx_665_0_ + MAPKK_p_p_659_0_ + MAPK_p_p_621_0_ + MAPKKthr_664_0_ 2 691.176470588 - -28.9156626506 + 28.9156626506 pink red - + - - + + - kinetics_479_0_ * k3*MAPKKthr_cplx_692_0_ + kinetics_451_0_ * k3*MAPKKthr_cplx_665_0_ - kinetics_479_0_ + kinetics_451_0_ k3 - MAPKKthr_cplx_692_0_ + MAPKKthr_cplx_665_0_ @@ -10767,7 +11214,7 @@ - + Kinetics are the same as for the craf-1* activity, ie., k1=1.1e-6, k2=.42, k3 =0.105 These are based on Force et al PNAS USA 91 1270-1274 1994. These parms cannot reach the observed 4X stim of MAPK. So lets increase the affinity, ie, raise k1 10X to 1.1e-5 Lets take it back down to where it was. Back up to 5X: 5.5e-6 @@ -10775,46 +11222,46 @@ - Raf_p_GTP_Ras_696_0_ - MAPKK_678_0_ - Raf_p_GTP_Ras_dot_1_cplx_699_0_ - Raf_p_GTP_Ras_dot_1_698_0_ + Raf_p_GTP_Ras_669_0_ + MAPKK_651_0_ + Raf_p_GTP_Ras_dot_1_cplx_672_0_ + Raf_p_GTP_Ras_dot_1_671_0_ 1 595.588235294 - -125.301204819 + 125.301204819 red red - - + + - + - kinetics_479_0_ * ( k1 * Raf_p_GTP_Ras_696_0_*MAPKK_678_0_ - k2 * Raf_p_GTP_Ras_dot_1_cplx_699_0_ ) + kinetics_451_0_ * ( k1 * MAPKK_651_0_*Raf_p_GTP_Ras_669_0_ - k2 * Raf_p_GTP_Ras_dot_1_cplx_672_0_ ) - kinetics_479_0_ + kinetics_451_0_ k1 - Raf_p_GTP_Ras_696_0_ - MAPKK_678_0_ + MAPKK_651_0_ + Raf_p_GTP_Ras_669_0_ k2 - Raf_p_GTP_Ras_dot_1_cplx_699_0_ + Raf_p_GTP_Ras_dot_1_cplx_672_0_ @@ -10825,39 +11272,39 @@ - + - Raf_p_GTP_Ras_dot_1_cplx_699_0_ - Raf_p_GTP_Ras_696_0_ - MAPKK_p_694_0_ - Raf_p_GTP_Ras_dot_1_698_0_ + Raf_p_GTP_Ras_dot_1_cplx_672_0_ + Raf_p_GTP_Ras_669_0_ + MAPKK_p_667_0_ + Raf_p_GTP_Ras_dot_1_671_0_ 2 595.588235294 - -125.301204819 + 125.301204819 red red - + - - + + - kinetics_479_0_ * k3*Raf_p_GTP_Ras_dot_1_cplx_699_0_ + kinetics_451_0_ * k3*Raf_p_GTP_Ras_dot_1_cplx_672_0_ - kinetics_479_0_ + kinetics_451_0_ k3 - Raf_p_GTP_Ras_dot_1_cplx_699_0_ + Raf_p_GTP_Ras_dot_1_cplx_672_0_ @@ -10865,7 +11312,7 @@ - + Same kinetics as other c-raf activated forms. See Force et al PNAS 91 1270-1274 1994. k1 = 1.1e-6, k2 = .42, k3 = 1.05 raise k1 to 5.5e-6 @@ -10873,46 +11320,46 @@ - Raf_p_GTP_Ras_696_0_ - MAPKK_p_694_0_ - Raf_p_GTP_Ras_dot_2_cplx_702_0_ - Raf_p_GTP_Ras_dot_2_701_0_ + Raf_p_GTP_Ras_669_0_ + MAPKK_p_667_0_ + Raf_p_GTP_Ras_dot_2_cplx_675_0_ + Raf_p_GTP_Ras_dot_2_674_0_ 1 595.588235294 - -115.662650602 + 115.662650602 red red - - + + - + - kinetics_479_0_ * ( k1 * Raf_p_GTP_Ras_696_0_*MAPKK_p_694_0_ - k2 * Raf_p_GTP_Ras_dot_2_cplx_702_0_ ) + kinetics_451_0_ * ( k1 * MAPKK_p_667_0_*Raf_p_GTP_Ras_669_0_ - k2 * Raf_p_GTP_Ras_dot_2_cplx_675_0_ ) - kinetics_479_0_ + kinetics_451_0_ k1 - Raf_p_GTP_Ras_696_0_ - MAPKK_p_694_0_ + MAPKK_p_667_0_ + Raf_p_GTP_Ras_669_0_ k2 - Raf_p_GTP_Ras_dot_2_cplx_702_0_ + Raf_p_GTP_Ras_dot_2_cplx_675_0_ @@ -10923,39 +11370,39 @@ - + - Raf_p_GTP_Ras_dot_2_cplx_702_0_ - Raf_p_GTP_Ras_696_0_ - MAPKK_p_p_686_0_ - Raf_p_GTP_Ras_dot_2_701_0_ + Raf_p_GTP_Ras_dot_2_cplx_675_0_ + Raf_p_GTP_Ras_669_0_ + MAPKK_p_p_659_0_ + Raf_p_GTP_Ras_dot_2_674_0_ 2 595.588235294 - -115.662650602 + 115.662650602 red red - + - - + + - kinetics_479_0_ * k3*Raf_p_GTP_Ras_dot_2_cplx_702_0_ + kinetics_451_0_ * k3*Raf_p_GTP_Ras_dot_2_cplx_675_0_ - kinetics_479_0_ + kinetics_451_0_ k3 - Raf_p_GTP_Ras_dot_2_cplx_702_0_ + Raf_p_GTP_Ras_dot_2_cplx_675_0_ @@ -10963,7 +11410,7 @@ - + Kinetics based on the activation of Gq by the receptor complex in the Gq model (in turn based on the Mahama and Linderman model) k1 = 2e-5, k2 = 1e-10, k3 = 10 (I do not know why they even bother with k2). Lets put k1 at 2e-6 to get a reasonable equilibrium More specific values from, eg.g: Orita et al JBC 268(34) 25542-25546 from rasGRF and smgGDS: k1=3.3e-7; k2 = 0.08, k3 = 0.02 @@ -10971,46 +11418,46 @@ - GEF_Gprot_bg_710_0_ - GDP_Ras_727_0_ - GEF_bg_act_Ras_cplx_713_0_ - GEF_bg_act_Ras_712_0_ + GEF_Gprot_bg_683_0_ + GDP_Ras_700_0_ + GEF_bg_act_Ras_cplx_686_0_ + GEF_bg_act_Ras_685_0_ 1 735.294117647 - -19.2771084337 + 19.2771084337 hotpink red - - + + - + - kinetics_479_0_ * ( k1 * GEF_Gprot_bg_710_0_*GDP_Ras_727_0_ - k2 * GEF_bg_act_Ras_cplx_713_0_ ) + kinetics_451_0_ * ( k1 * GEF_Gprot_bg_683_0_*GDP_Ras_700_0_ - k2 * GEF_bg_act_Ras_cplx_686_0_ ) - kinetics_479_0_ + kinetics_451_0_ k1 - GEF_Gprot_bg_710_0_ - GDP_Ras_727_0_ + GEF_Gprot_bg_683_0_ + GDP_Ras_700_0_ k2 - GEF_bg_act_Ras_cplx_713_0_ + GEF_bg_act_Ras_cplx_686_0_ @@ -11021,39 +11468,39 @@ - + - GEF_bg_act_Ras_cplx_713_0_ - GEF_Gprot_bg_710_0_ - GTP_Ras_725_0_ - GEF_bg_act_Ras_712_0_ + GEF_bg_act_Ras_cplx_686_0_ + GEF_Gprot_bg_683_0_ + GTP_Ras_698_0_ + GEF_bg_act_Ras_685_0_ 2 735.294117647 - -19.2771084337 + 19.2771084337 hotpink red - + - - + + - kinetics_479_0_ * k3*GEF_bg_act_Ras_cplx_713_0_ + kinetics_451_0_ * k3*GEF_bg_act_Ras_cplx_686_0_ - kinetics_479_0_ + kinetics_451_0_ k3 - GEF_bg_act_Ras_cplx_713_0_ + GEF_bg_act_Ras_cplx_686_0_ @@ -11061,49 +11508,49 @@ - + - inact_GEF_715_0_ - GDP_Ras_727_0_ - basal_GEF_activity_cplx_718_0_ - basal_GEF_activity_717_0_ + inact_GEF_688_0_ + GDP_Ras_700_0_ + basal_GEF_activity_cplx_691_0_ + basal_GEF_activity_690_0_ 1 750.0 - -19.2771084337 + 19.2771084337 red hotpink - - + + - + - kinetics_479_0_ * ( k1 * inact_GEF_715_0_*GDP_Ras_727_0_ - k2 * basal_GEF_activity_cplx_718_0_ ) + kinetics_451_0_ * ( k1 * inact_GEF_688_0_*GDP_Ras_700_0_ - k2 * basal_GEF_activity_cplx_691_0_ ) - kinetics_479_0_ + kinetics_451_0_ k1 - inact_GEF_715_0_ - GDP_Ras_727_0_ + inact_GEF_688_0_ + GDP_Ras_700_0_ k2 - basal_GEF_activity_cplx_718_0_ + basal_GEF_activity_cplx_691_0_ @@ -11114,39 +11561,39 @@ - + - basal_GEF_activity_cplx_718_0_ - inact_GEF_715_0_ - GTP_Ras_725_0_ - basal_GEF_activity_717_0_ + basal_GEF_activity_cplx_691_0_ + inact_GEF_688_0_ + GTP_Ras_698_0_ + basal_GEF_activity_690_0_ 2 750.0 - -19.2771084337 + 19.2771084337 red hotpink - + - - + + - kinetics_479_0_ * k3*basal_GEF_activity_cplx_718_0_ + kinetics_451_0_ * k3*basal_GEF_activity_cplx_691_0_ - kinetics_479_0_ + kinetics_451_0_ k3 - basal_GEF_activity_cplx_718_0_ + basal_GEF_activity_cplx_691_0_ @@ -11154,7 +11601,7 @@ - + Kinetics same as GEF-bg-act-ras @@ -11162,46 +11609,46 @@ - GEF_p_720_0_ - GDP_Ras_727_0_ - GEF_p_act_Ras_cplx_723_0_ - GEF_p_act_Ras_722_0_ + GEF_p_693_0_ + GDP_Ras_700_0_ + GEF_p_act_Ras_cplx_696_0_ + GEF_p_act_Ras_695_0_ 1 764.705882353 - -19.2771084337 + 19.2771084337 hotpink red - - + + - + - kinetics_479_0_ * ( k1 * GEF_p_720_0_*GDP_Ras_727_0_ - k2 * GEF_p_act_Ras_cplx_723_0_ ) + kinetics_451_0_ * ( k1 * GDP_Ras_700_0_*GEF_p_693_0_ - k2 * GEF_p_act_Ras_cplx_696_0_ ) - kinetics_479_0_ + kinetics_451_0_ k1 - GEF_p_720_0_ - GDP_Ras_727_0_ + GDP_Ras_700_0_ + GEF_p_693_0_ k2 - GEF_p_act_Ras_cplx_723_0_ + GEF_p_act_Ras_cplx_696_0_ @@ -11212,39 +11659,39 @@ - + - GEF_p_act_Ras_cplx_723_0_ - GEF_p_720_0_ - GTP_Ras_725_0_ - GEF_p_act_Ras_722_0_ + GEF_p_act_Ras_cplx_696_0_ + GEF_p_693_0_ + GTP_Ras_698_0_ + GEF_p_act_Ras_695_0_ 2 764.705882353 - -19.2771084337 + 19.2771084337 hotpink red - + - - + + - kinetics_479_0_ * k3*GEF_p_act_Ras_cplx_723_0_ + kinetics_451_0_ * k3*GEF_p_act_Ras_cplx_696_0_ - kinetics_479_0_ + kinetics_451_0_ k3 - GEF_p_act_Ras_cplx_723_0_ + GEF_p_act_Ras_cplx_696_0_ @@ -11252,7 +11699,7 @@ - + From Eccleston et al JBC 268(36)pp27012-19 get Kd _lessthan_ 2uM, kcat - 10/sec From Martin et al Cell 63 843-849 1990 get Kd ~ 250 nM, kcat = 20/min I will go with the Eccleston figures as there are good error bars (10%). In general the values are reasonably close. k1 = 1.666e-3/sec, k2 = 1000/sec, k3 = 10/sec (note k3 is rate-limiting) 5 Nov 2002: Changed ratio term to 4 from 100. Now we have k1=8.25e-5; k2=40, k3=10. k3 is still rate-limiting. @@ -11260,46 +11707,46 @@ - GAP_731_0_ - GTP_Ras_725_0_ - GAP_inact_Ras_cplx_734_0_ - GAP_inact_Ras_733_0_ + GAP_704_0_ + GTP_Ras_698_0_ + GAP_inact_Ras_cplx_707_0_ + GAP_inact_Ras_706_0_ 1 823.529411765 - -19.2771084337 + 19.2771084337 red red - - + + - + - kinetics_479_0_ * ( k1 * GAP_731_0_*GTP_Ras_725_0_ - k2 * GAP_inact_Ras_cplx_734_0_ ) + kinetics_451_0_ * ( k1 * GAP_704_0_*GTP_Ras_698_0_ - k2 * GAP_inact_Ras_cplx_707_0_ ) - kinetics_479_0_ + kinetics_451_0_ k1 - GAP_731_0_ - GTP_Ras_725_0_ + GAP_704_0_ + GTP_Ras_698_0_ k2 - GAP_inact_Ras_cplx_734_0_ + GAP_inact_Ras_cplx_707_0_ @@ -11310,39 +11757,39 @@ - + - GAP_inact_Ras_cplx_734_0_ - GAP_731_0_ - GDP_Ras_727_0_ - GAP_inact_Ras_733_0_ + GAP_inact_Ras_cplx_707_0_ + GAP_704_0_ + GDP_Ras_700_0_ + GAP_inact_Ras_706_0_ 2 823.529411765 - -19.2771084337 + 19.2771084337 red red - + - - + + - kinetics_479_0_ * k3*GAP_inact_Ras_cplx_734_0_ + kinetics_451_0_ * k3*GAP_inact_Ras_cplx_707_0_ - kinetics_479_0_ + kinetics_451_0_ k3 - GAP_inact_Ras_cplx_734_0_ + GAP_inact_Ras_cplx_707_0_ @@ -11350,7 +11797,7 @@ - + Kinetics same as GEF-bg_act-ras @@ -11358,46 +11805,46 @@ - CaM_GEF_738_0_ - GDP_Ras_727_0_ - CaM_GEF_act_Ras_cplx_741_0_ - CaM_GEF_act_Ras_740_0_ + CaM_GEF_711_0_ + GDP_Ras_700_0_ + CaM_GEF_act_Ras_cplx_714_0_ + CaM_GEF_act_Ras_713_0_ 1 852.941176471 - -19.2771084337 + 19.2771084337 pink red - - + + - + - kinetics_479_0_ * ( k1 * CaM_GEF_738_0_*GDP_Ras_727_0_ - k2 * CaM_GEF_act_Ras_cplx_741_0_ ) + kinetics_451_0_ * ( k1 * GDP_Ras_700_0_*CaM_GEF_711_0_ - k2 * CaM_GEF_act_Ras_cplx_714_0_ ) - kinetics_479_0_ + kinetics_451_0_ k1 - CaM_GEF_738_0_ - GDP_Ras_727_0_ + GDP_Ras_700_0_ + CaM_GEF_711_0_ k2 - CaM_GEF_act_Ras_cplx_741_0_ + CaM_GEF_act_Ras_cplx_714_0_ @@ -11408,39 +11855,39 @@ - + - CaM_GEF_act_Ras_cplx_741_0_ - CaM_GEF_738_0_ - GTP_Ras_725_0_ - CaM_GEF_act_Ras_740_0_ + CaM_GEF_act_Ras_cplx_714_0_ + CaM_GEF_711_0_ + GTP_Ras_698_0_ + CaM_GEF_act_Ras_713_0_ 2 852.941176471 - -19.2771084337 + 19.2771084337 pink red - + - - + + - kinetics_479_0_ * k3*CaM_GEF_act_Ras_cplx_741_0_ + kinetics_451_0_ * k3*CaM_GEF_act_Ras_cplx_714_0_ - kinetics_479_0_ + kinetics_451_0_ k3 - CaM_GEF_act_Ras_cplx_741_0_ + CaM_GEF_act_Ras_cplx_714_0_ @@ -11448,7 +11895,7 @@ - + Hsu et al JBC 266:1 603-608 1991 Km = 385 +- 100 uM, Vm = 5.1 +-1 pmol/min/ug for PLC-771. Other sites have similar range, but are not stim as much by EGF. k1 = 2.8e-2/385/6e5 = 1.2e-10. Phenomenally slow. But Sherrill and Kyte say turnover # for angiotensin II is 5/min for cell extt, and 2/min for placental. Also see Okada et al for Shc rates which are much faster. @@ -11456,46 +11903,46 @@ - L_dot_EGFR_761_0_ - Ca_dot_PLC_g_818_0_ - Ca_dot_PLC_g_phospho_cplx_764_0_ - Ca_dot_PLC_g_phospho_763_0_ + L_dot_EGFR_734_0_ + Ca_dot_PLC_g_791_0_ + Ca_dot_PLC_g_phospho_cplx_737_0_ + Ca_dot_PLC_g_phospho_736_0_ 1 897.058823529 - -19.2771084337 + 19.2771084337 red red - - + + - + - kinetics_479_0_ * ( k1 * L_dot_EGFR_761_0_*Ca_dot_PLC_g_818_0_ - k2 * Ca_dot_PLC_g_phospho_cplx_764_0_ ) + kinetics_451_0_ * ( k1 * L_dot_EGFR_734_0_*Ca_dot_PLC_g_791_0_ - k2 * Ca_dot_PLC_g_phospho_cplx_737_0_ ) - kinetics_479_0_ + kinetics_451_0_ k1 - L_dot_EGFR_761_0_ - Ca_dot_PLC_g_818_0_ + L_dot_EGFR_734_0_ + Ca_dot_PLC_g_791_0_ k2 - Ca_dot_PLC_g_phospho_cplx_764_0_ + Ca_dot_PLC_g_phospho_cplx_737_0_ @@ -11506,39 +11953,39 @@ - + - Ca_dot_PLC_g_phospho_cplx_764_0_ - L_dot_EGFR_761_0_ - Ca_dot_PLC_g_p_822_0_ - Ca_dot_PLC_g_phospho_763_0_ + Ca_dot_PLC_g_phospho_cplx_737_0_ + L_dot_EGFR_734_0_ + Ca_dot_PLC_g_p_795_0_ + Ca_dot_PLC_g_phospho_736_0_ 2 897.058823529 - -19.2771084337 + 19.2771084337 red red - + - - + + - kinetics_479_0_ * k3*Ca_dot_PLC_g_phospho_cplx_764_0_ + kinetics_451_0_ * k3*Ca_dot_PLC_g_phospho_cplx_737_0_ - kinetics_479_0_ + kinetics_451_0_ k3 - Ca_dot_PLC_g_phospho_cplx_764_0_ + Ca_dot_PLC_g_phospho_cplx_737_0_ @@ -11546,7 +11993,7 @@ - + Rates from Okada et al JBC 270:35 pp 20737 1995 Km = 0.70 to 0.85 uM, Vmax = 4.4 to 5.0 pmol/min. Unfortunately the amount of enzyme is not known, the prep is only partially purified. Time course of phosph is max within 30 sec, falls back within 20 min. Ref: Sasaoka et al JBC 269:51 32621 1994. Use k3 = 0.1 based on this tau. @@ -11554,46 +12001,46 @@ - L_dot_EGFR_761_0_ - SHC_784_0_ - SHC_phospho_cplx_767_0_ - SHC_phospho_766_0_ + L_dot_EGFR_734_0_ + SHC_757_0_ + SHC_phospho_cplx_740_0_ + SHC_phospho_739_0_ 1 897.058823529 - -28.9156626506 + 28.9156626506 red red - - + + - + - kinetics_479_0_ * ( k1 * SHC_784_0_*L_dot_EGFR_761_0_ - k2 * SHC_phospho_cplx_767_0_ ) + kinetics_451_0_ * ( k1 * SHC_757_0_*L_dot_EGFR_734_0_ - k2 * SHC_phospho_cplx_740_0_ ) - kinetics_479_0_ + kinetics_451_0_ k1 - SHC_784_0_ - L_dot_EGFR_761_0_ + SHC_757_0_ + L_dot_EGFR_734_0_ k2 - SHC_phospho_cplx_767_0_ + SHC_phospho_cplx_740_0_ @@ -11604,39 +12051,39 @@ - + - SHC_phospho_cplx_767_0_ - L_dot_EGFR_761_0_ - SHC_p_786_0_ - SHC_phospho_766_0_ + SHC_phospho_cplx_740_0_ + L_dot_EGFR_734_0_ + SHC_p_759_0_ + SHC_phospho_739_0_ 2 897.058823529 - -28.9156626506 + 28.9156626506 red red - + - - + + - kinetics_479_0_ * k3*SHC_phospho_cplx_767_0_ + kinetics_451_0_ * k3*SHC_phospho_cplx_740_0_ - kinetics_479_0_ + kinetics_451_0_ k3 - SHC_phospho_cplx_767_0_ + SHC_phospho_cplx_740_0_ @@ -11644,49 +12091,49 @@ - + - SHC_p_dot_Sos_dot_Grb2_779_0_ - GDP_Ras_727_0_ - Sos_dot_Ras_GEF_cplx_782_0_ - Sos_dot_Ras_GEF_781_0_ + SHC_p_dot_Sos_dot_Grb2_752_0_ + GDP_Ras_700_0_ + Sos_dot_Ras_GEF_cplx_755_0_ + Sos_dot_Ras_GEF_754_0_ 1 0.0 - -212.048192771 + 212.048192771 brown red - - + + - + - kinetics_479_0_ * ( k1 * SHC_p_dot_Sos_dot_Grb2_779_0_*GDP_Ras_727_0_ - k2 * Sos_dot_Ras_GEF_cplx_782_0_ ) + kinetics_451_0_ * ( k1 * SHC_p_dot_Sos_dot_Grb2_752_0_*GDP_Ras_700_0_ - k2 * Sos_dot_Ras_GEF_cplx_755_0_ ) - kinetics_479_0_ + kinetics_451_0_ k1 - SHC_p_dot_Sos_dot_Grb2_779_0_ - GDP_Ras_727_0_ + SHC_p_dot_Sos_dot_Grb2_752_0_ + GDP_Ras_700_0_ k2 - Sos_dot_Ras_GEF_cplx_782_0_ + Sos_dot_Ras_GEF_cplx_755_0_ @@ -11697,39 +12144,39 @@ - + - Sos_dot_Ras_GEF_cplx_782_0_ - SHC_p_dot_Sos_dot_Grb2_779_0_ - GTP_Ras_725_0_ - Sos_dot_Ras_GEF_781_0_ + Sos_dot_Ras_GEF_cplx_755_0_ + SHC_p_dot_Sos_dot_Grb2_752_0_ + GTP_Ras_698_0_ + Sos_dot_Ras_GEF_754_0_ 2 0.0 - -212.048192771 + 212.048192771 brown red - + - - + + - kinetics_479_0_ * k3*Sos_dot_Ras_GEF_cplx_782_0_ + kinetics_451_0_ * k3*Sos_dot_Ras_GEF_cplx_755_0_ - kinetics_479_0_ + kinetics_451_0_ k3 - Sos_dot_Ras_GEF_cplx_782_0_ + Sos_dot_Ras_GEF_cplx_755_0_ @@ -11737,7 +12184,7 @@ - + Mainly Homma et al JBC 263:14 1988 pp 6592, but these parms are the Ca-stimulated form. It is not clear whether the enzyme is activated by tyrosine phosphorylation at this point or not. Wahl et al JBC 267:15 10447-10456 1992 say that the Ca_stim and phosph form has 7X higher affinity for substrate than control. This is close to Wahl's figure 7, which I am using as reference. @@ -11746,43 +12193,43 @@ 176.470588235 - -212.048192771 + 212.048192771 pink red - + - - + + - + - kinetics_479_0_ * ( kcat * PIP2_636_0_ * Ca_dot_PLC_g_818_0_ / ( Km + PIP2_636_0_)) + kinetics_451_0_ * ( kcat * PIP2_609_0_ * Ca_dot_PLC_g_791_0_ / ( Km + PIP2_609_0_)) - kinetics_479_0_ + kinetics_451_0_ kcat - PIP2_636_0_ - Ca_dot_PLC_g_818_0_ + PIP2_609_0_ + Ca_dot_PLC_g_791_0_ Km - PIP2_636_0_ + PIP2_609_0_ @@ -11793,7 +12240,7 @@ - + Mainly Homma et al JBC 263:14 1988 pp 6592, but these parms are the Ca-stimulated form. It is not clear whether the enzyme is activated by tyrosine phosphorylation at this point or not. Wahl et al JBC 267:15 10447-10456 1992 say that this has 7X higher affinity for substrate than control. @@ -11802,43 +12249,43 @@ 191.176470588 - -212.048192771 + 212.048192771 pink red - + - - + + - + - kinetics_479_0_ * ( kcat * PIP2_636_0_ * Ca_dot_PLC_g_p_822_0_ / ( Km + PIP2_636_0_)) + kinetics_451_0_ * ( kcat * PIP2_609_0_ * Ca_dot_PLC_g_p_795_0_ / ( Km + PIP2_609_0_)) - kinetics_479_0_ + kinetics_451_0_ kcat - PIP2_636_0_ - Ca_dot_PLC_g_p_822_0_ + PIP2_609_0_ + Ca_dot_PLC_g_p_795_0_ Km - PIP2_636_0_ + PIP2_609_0_ @@ -11849,49 +12296,49 @@ - + - PLCg_basal_826_0_ - PLC_g_814_0_ - PLC_g_phospho_cplx_829_0_ - PLC_g_phospho_828_0_ + PLCg_basal_799_0_ + PLC_g_787_0_ + PLC_g_phospho_cplx_802_0_ + PLC_g_phospho_801_0_ 1 205.882352941 - -212.048192771 + 212.048192771 red 33 - - + + - + - kinetics_479_0_ * ( k1 * PLCg_basal_826_0_*PLC_g_814_0_ - k2 * PLC_g_phospho_cplx_829_0_ ) + kinetics_451_0_ * ( k1 * PLC_g_787_0_*PLCg_basal_799_0_ - k2 * PLC_g_phospho_cplx_802_0_ ) - kinetics_479_0_ + kinetics_451_0_ k1 - PLCg_basal_826_0_ - PLC_g_814_0_ + PLC_g_787_0_ + PLCg_basal_799_0_ k2 - PLC_g_phospho_cplx_829_0_ + PLC_g_phospho_cplx_802_0_ @@ -11902,39 +12349,39 @@ - + - PLC_g_phospho_cplx_829_0_ - PLCg_basal_826_0_ - PLC_g_p_816_0_ - PLC_g_phospho_828_0_ + PLC_g_phospho_cplx_802_0_ + PLCg_basal_799_0_ + PLC_g_p_789_0_ + PLC_g_phospho_801_0_ 2 205.882352941 - -212.048192771 + 212.048192771 red 33 - + - - + + - kinetics_479_0_ * k3*PLC_g_phospho_cplx_829_0_ + kinetics_451_0_ * k3*PLC_g_phospho_cplx_802_0_ - kinetics_479_0_ + kinetics_451_0_ k3 - PLC_g_phospho_cplx_829_0_ + PLC_g_phospho_cplx_802_0_ @@ -11942,7 +12389,7 @@ - + Rates from autocamtide phosphorylation, from Hanson and Schulman JBC 267:24 17216-17224 1992. Jan 1 1998: Speed up 12x to match fig 5. @@ -11950,46 +12397,46 @@ - tot_CaM_CaMKII_853_0_ - CaMKII_thr286_849_0_ - CaM_act_305_cplx_856_0_ - CaM_act_305_855_0_ + tot_CaM_CaMKII_826_0_ + CaMKII_thr286_822_0_ + CaM_act_305_cplx_829_0_ + CaM_act_305_828_0_ 1 316.176470588 - -308.43373494 + 308.43373494 green red - - + + - + - kinetics_479_0_ * ( k1 * CaMKII_thr286_849_0_*tot_CaM_CaMKII_853_0_ - k2 * CaM_act_305_cplx_856_0_ ) + kinetics_451_0_ * ( k1 * tot_CaM_CaMKII_826_0_*CaMKII_thr286_822_0_ - k2 * CaM_act_305_cplx_829_0_ ) - kinetics_479_0_ + kinetics_451_0_ k1 - CaMKII_thr286_849_0_ - tot_CaM_CaMKII_853_0_ + tot_CaM_CaMKII_826_0_ + CaMKII_thr286_822_0_ k2 - CaM_act_305_cplx_856_0_ + CaM_act_305_cplx_829_0_ @@ -12000,39 +12447,39 @@ - + - CaM_act_305_cplx_856_0_ - tot_CaM_CaMKII_853_0_ - CaMKII_p_p_p_847_0_ - CaM_act_305_855_0_ + CaM_act_305_cplx_829_0_ + tot_CaM_CaMKII_826_0_ + CaMKII_p_p_p_820_0_ + CaM_act_305_828_0_ 2 316.176470588 - -308.43373494 + 308.43373494 green red - + - - + + - kinetics_479_0_ * k3*CaM_act_305_cplx_856_0_ + kinetics_451_0_ * k3*CaM_act_305_cplx_829_0_ - kinetics_479_0_ + kinetics_451_0_ k3 - CaM_act_305_cplx_856_0_ + CaM_act_305_cplx_829_0_ @@ -12040,49 +12487,49 @@ - + - tot_CaM_CaMKII_853_0_ - CaMKII_CaM_843_0_ - CaM_act_286_cplx_859_0_ - CaM_act_286_858_0_ + tot_CaM_CaMKII_826_0_ + CaMKII_CaM_816_0_ + CaM_act_286_cplx_832_0_ + CaM_act_286_831_0_ 1 316.176470588 - -318.072289157 + 318.072289157 green red - - + + - + - kinetics_479_0_ * ( k1 * CaMKII_CaM_843_0_*tot_CaM_CaMKII_853_0_ - k2 * CaM_act_286_cplx_859_0_ ) + kinetics_451_0_ * ( k1 * CaMKII_CaM_816_0_*tot_CaM_CaMKII_826_0_ - k2 * CaM_act_286_cplx_832_0_ ) - kinetics_479_0_ + kinetics_451_0_ k1 - CaMKII_CaM_843_0_ - tot_CaM_CaMKII_853_0_ + CaMKII_CaM_816_0_ + tot_CaM_CaMKII_826_0_ k2 - CaM_act_286_cplx_859_0_ + CaM_act_286_cplx_832_0_ @@ -12093,39 +12540,39 @@ - + - CaM_act_286_cplx_859_0_ - tot_CaM_CaMKII_853_0_ - CaMKII_thr286_p_CaM_845_0_ - CaM_act_286_858_0_ + CaM_act_286_cplx_832_0_ + tot_CaM_CaMKII_826_0_ + CaMKII_thr286_p_CaM_818_0_ + CaM_act_286_831_0_ 2 316.176470588 - -318.072289157 + 318.072289157 green red - + - - + + - kinetics_479_0_ * k3*CaM_act_286_cplx_859_0_ + kinetics_451_0_ * k3*CaM_act_286_cplx_832_0_ - kinetics_479_0_ + kinetics_451_0_ k3 - CaM_act_286_cplx_859_0_ + CaM_act_286_cplx_832_0_ @@ -12133,7 +12580,7 @@ - + See Hanson and Schulman again, for afterburst rates of phosph. @@ -12141,46 +12588,46 @@ - tot_autonomous_CaMKII_861_0_ - CaMKII_thr286_849_0_ - auton_305_cplx_864_0_ - auton_305_863_0_ + tot_autonomous_CaMKII_834_0_ + CaMKII_thr286_822_0_ + auton_305_cplx_837_0_ + auton_305_836_0_ 1 375.0 - -308.43373494 + 308.43373494 green red - - + + - + - kinetics_479_0_ * ( k1 * CaMKII_thr286_849_0_*tot_autonomous_CaMKII_861_0_ - k2 * auton_305_cplx_864_0_ ) + kinetics_451_0_ * ( k1 * tot_autonomous_CaMKII_834_0_*CaMKII_thr286_822_0_ - k2 * auton_305_cplx_837_0_ ) - kinetics_479_0_ + kinetics_451_0_ k1 - CaMKII_thr286_849_0_ - tot_autonomous_CaMKII_861_0_ + tot_autonomous_CaMKII_834_0_ + CaMKII_thr286_822_0_ k2 - auton_305_cplx_864_0_ + auton_305_cplx_837_0_ @@ -12191,39 +12638,39 @@ - + - auton_305_cplx_864_0_ - tot_autonomous_CaMKII_861_0_ - CaMKII_p_p_p_847_0_ - auton_305_863_0_ + auton_305_cplx_837_0_ + tot_autonomous_CaMKII_834_0_ + CaMKII_p_p_p_820_0_ + auton_305_836_0_ 2 375.0 - -308.43373494 + 308.43373494 green red - + - - + + - kinetics_479_0_ * k3*auton_305_cplx_864_0_ + kinetics_451_0_ * k3*auton_305_cplx_837_0_ - kinetics_479_0_ + kinetics_451_0_ k3 - auton_305_cplx_864_0_ + auton_305_cplx_837_0_ @@ -12231,49 +12678,49 @@ - + - tot_autonomous_CaMKII_861_0_ - CaMKII_CaM_843_0_ - auton_286_cplx_867_0_ - auton_286_866_0_ + tot_autonomous_CaMKII_834_0_ + CaMKII_CaM_816_0_ + auton_286_cplx_840_0_ + auton_286_839_0_ 1 375.0 - -318.072289157 + 318.072289157 green red - - + + - + - kinetics_479_0_ * ( k1 * CaMKII_CaM_843_0_*tot_autonomous_CaMKII_861_0_ - k2 * auton_286_cplx_867_0_ ) + kinetics_451_0_ * ( k1 * CaMKII_CaM_816_0_*tot_autonomous_CaMKII_834_0_ - k2 * auton_286_cplx_840_0_ ) - kinetics_479_0_ + kinetics_451_0_ k1 - CaMKII_CaM_843_0_ - tot_autonomous_CaMKII_861_0_ + CaMKII_CaM_816_0_ + tot_autonomous_CaMKII_834_0_ k2 - auton_286_cplx_867_0_ + auton_286_cplx_840_0_ @@ -12284,39 +12731,39 @@ - + - auton_286_cplx_867_0_ - tot_autonomous_CaMKII_861_0_ - CaMKII_thr286_p_CaM_845_0_ - auton_286_866_0_ + auton_286_cplx_840_0_ + tot_autonomous_CaMKII_834_0_ + CaMKII_thr286_p_CaM_818_0_ + auton_286_839_0_ 2 375.0 - -318.072289157 + 318.072289157 green red - + - - + + - kinetics_479_0_ * k3*auton_286_cplx_867_0_ + kinetics_451_0_ * k3*auton_286_cplx_840_0_ - kinetics_479_0_ + kinetics_451_0_ k3 - auton_286_cplx_867_0_ + auton_286_cplx_840_0_ @@ -12324,7 +12771,7 @@ - + From Seki et al ABB 316(2):673-679 @@ -12332,46 +12779,46 @@ - CaM_bo_Ca_bc_n_CaNAB_889_0_ - neurogranin_p_883_0_ - dephosph_neurogranin_cplx_892_0_ - dephosph_neurogranin_891_0_ + CaM_bo_Ca_bc_n_CaNAB_862_0_ + neurogranin_p_856_0_ + dephosph_neurogranin_cplx_865_0_ + dephosph_neurogranin_864_0_ 1 544.117647059 - -212.048192771 + 212.048192771 darkblue red - - + + - + - kinetics_479_0_ * ( k1 * CaM_bo_Ca_bc_n_CaNAB_889_0_*neurogranin_p_883_0_ - k2 * dephosph_neurogranin_cplx_892_0_ ) + kinetics_451_0_ * ( k1 * neurogranin_p_856_0_*CaM_bo_Ca_bc_n_CaNAB_862_0_ - k2 * dephosph_neurogranin_cplx_865_0_ ) - kinetics_479_0_ + kinetics_451_0_ k1 - CaM_bo_Ca_bc_n_CaNAB_889_0_ - neurogranin_p_883_0_ + neurogranin_p_856_0_ + CaM_bo_Ca_bc_n_CaNAB_862_0_ k2 - dephosph_neurogranin_cplx_892_0_ + dephosph_neurogranin_cplx_865_0_ @@ -12382,39 +12829,39 @@ - + - dephosph_neurogranin_cplx_892_0_ - CaM_bo_Ca_bc_n_CaNAB_889_0_ - neurogranin_885_0_ - dephosph_neurogranin_891_0_ + dephosph_neurogranin_cplx_865_0_ + CaM_bo_Ca_bc_n_CaNAB_862_0_ + neurogranin_858_0_ + dephosph_neurogranin_864_0_ 2 544.117647059 - -212.048192771 + 212.048192771 darkblue red - + - - + + - kinetics_479_0_ * k3*dephosph_neurogranin_cplx_892_0_ + kinetics_451_0_ * k3*dephosph_neurogranin_cplx_865_0_ - kinetics_479_0_ + kinetics_451_0_ k3 - dephosph_neurogranin_cplx_892_0_ + dephosph_neurogranin_cplx_865_0_ @@ -12422,49 +12869,49 @@ - + - CaM_bo_Ca_bc_n_CaNAB_889_0_ - I1_p_944_0_ - dephosph_inhib1_cplx_895_0_ - dephosph_inhib1_894_0_ + CaM_bo_Ca_bc_n_CaNAB_862_0_ + I1_p_917_0_ + dephosph_inhib1_cplx_868_0_ + dephosph_inhib1_867_0_ 1 544.117647059 - -221.686746988 + 221.686746988 darkblue red - - + + - + - kinetics_479_0_ * ( k1 * I1_p_944_0_*CaM_bo_Ca_bc_n_CaNAB_889_0_ - k2 * dephosph_inhib1_cplx_895_0_ ) + kinetics_451_0_ * ( k1 * I1_p_917_0_*CaM_bo_Ca_bc_n_CaNAB_862_0_ - k2 * dephosph_inhib1_cplx_868_0_ ) - kinetics_479_0_ + kinetics_451_0_ k1 - I1_p_944_0_ - CaM_bo_Ca_bc_n_CaNAB_889_0_ + I1_p_917_0_ + CaM_bo_Ca_bc_n_CaNAB_862_0_ k2 - dephosph_inhib1_cplx_895_0_ + dephosph_inhib1_cplx_868_0_ @@ -12475,39 +12922,39 @@ - + - dephosph_inhib1_cplx_895_0_ - CaM_bo_Ca_bc_n_CaNAB_889_0_ - I1_942_0_ - dephosph_inhib1_894_0_ + dephosph_inhib1_cplx_868_0_ + CaM_bo_Ca_bc_n_CaNAB_862_0_ + I1_915_0_ + dephosph_inhib1_867_0_ 2 544.117647059 - -221.686746988 + 221.686746988 darkblue red - + - - + + - kinetics_479_0_ * k3*dephosph_inhib1_cplx_895_0_ + kinetics_451_0_ * k3*dephosph_inhib1_cplx_868_0_ - kinetics_479_0_ + kinetics_451_0_ k3 - dephosph_inhib1_cplx_895_0_ + dephosph_inhib1_cplx_868_0_ @@ -12515,49 +12962,49 @@ - + - CaM_bo_Ca_bc_n_CaNAB_889_0_ - PP1_I1_p_946_0_ - dephosph_PP1_I_p_cplx_898_0_ - dephosph_PP1_I_p_897_0_ + CaM_bo_Ca_bc_n_CaNAB_862_0_ + PP1_I1_p_919_0_ + dephosph_PP1_I_p_cplx_871_0_ + dephosph_PP1_I_p_870_0_ 1 544.117647059 - -231.325301205 + 231.325301205 darkblue white - - + + - + - kinetics_479_0_ * ( k1 * CaM_bo_Ca_bc_n_CaNAB_889_0_*PP1_I1_p_946_0_ - k2 * dephosph_PP1_I_p_cplx_898_0_ ) + kinetics_451_0_ * ( k1 * CaM_bo_Ca_bc_n_CaNAB_862_0_*PP1_I1_p_919_0_ - k2 * dephosph_PP1_I_p_cplx_871_0_ ) - kinetics_479_0_ + kinetics_451_0_ k1 - CaM_bo_Ca_bc_n_CaNAB_889_0_ - PP1_I1_p_946_0_ + CaM_bo_Ca_bc_n_CaNAB_862_0_ + PP1_I1_p_919_0_ k2 - dephosph_PP1_I_p_cplx_898_0_ + dephosph_PP1_I_p_cplx_871_0_ @@ -12568,39 +13015,39 @@ - + - dephosph_PP1_I_p_cplx_898_0_ - CaM_bo_Ca_bc_n_CaNAB_889_0_ - PP1_I1_948_0_ - dephosph_PP1_I_p_897_0_ + dephosph_PP1_I_p_cplx_871_0_ + CaM_bo_Ca_bc_n_CaNAB_862_0_ + PP1_I1_921_0_ + dephosph_PP1_I_p_870_0_ 2 544.117647059 - -231.325301205 + 231.325301205 darkblue white - + - - + + - kinetics_479_0_ * k3*dephosph_PP1_I_p_cplx_898_0_ + kinetics_451_0_ * k3*dephosph_PP1_I_p_cplx_871_0_ - kinetics_479_0_ + kinetics_451_0_ k3 - dephosph_PP1_I_p_cplx_898_0_ + dephosph_PP1_I_p_cplx_871_0_ @@ -12608,7 +13055,7 @@ - + The rates here are so slow I do not know if we should even bother with this enz reacn. These numbers are from Liu and Storm. Other refs suggest that the Km stays the same but the Vmax goes to 10% of the CaM stim levels. Prev: k1=2.2e-9, k2 = 0.0052, k3 = 0.0013 New : k1=5.7e-8, k2=.136, k3=.034 @@ -12616,46 +13063,46 @@ - CaNAB_Ca4_900_0_ - I1_p_944_0_ - dephosph_inhib1_noCaM_cplx_903_0_ - dephosph_inhib1_noCaM_902_0_ + CaNAB_Ca4_873_0_ + I1_p_917_0_ + dephosph_inhib1_noCaM_cplx_876_0_ + dephosph_inhib1_noCaM_875_0_ 1 558.823529412 - -212.048192771 + 212.048192771 tan red - - + + - + - kinetics_479_0_ * ( k1 * I1_p_944_0_*CaNAB_Ca4_900_0_ - k2 * dephosph_inhib1_noCaM_cplx_903_0_ ) + kinetics_451_0_ * ( k1 * CaNAB_Ca4_873_0_*I1_p_917_0_ - k2 * dephosph_inhib1_noCaM_cplx_876_0_ ) - kinetics_479_0_ + kinetics_451_0_ k1 - I1_p_944_0_ - CaNAB_Ca4_900_0_ + CaNAB_Ca4_873_0_ + I1_p_917_0_ k2 - dephosph_inhib1_noCaM_cplx_903_0_ + dephosph_inhib1_noCaM_cplx_876_0_ @@ -12666,39 +13113,39 @@ - + - dephosph_inhib1_noCaM_cplx_903_0_ - CaNAB_Ca4_900_0_ - I1_942_0_ - dephosph_inhib1_noCaM_902_0_ + dephosph_inhib1_noCaM_cplx_876_0_ + CaNAB_Ca4_873_0_ + I1_915_0_ + dephosph_inhib1_noCaM_875_0_ 2 558.823529412 - -212.048192771 + 212.048192771 tan red - + - - + + - kinetics_479_0_ * k3*dephosph_inhib1_noCaM_cplx_903_0_ + kinetics_451_0_ * k3*dephosph_inhib1_noCaM_cplx_876_0_ - kinetics_479_0_ + kinetics_451_0_ k3 - dephosph_inhib1_noCaM_cplx_903_0_ + dephosph_inhib1_noCaM_cplx_876_0_ @@ -12706,7 +13153,7 @@ - + The rates are from Stralfors et al Eur J Biochem 149 295-303 giving Vmax = 5.7 umol/min giving k3 = 3.5/sec and k2 = 14. Foulkes et al Eur J Biochem 132 309-313 1983 give Km = 5.1 uM so k1 becomes 5.72e-6 Simonelli 1984 (Grad Thesis, CUNY) showed that other substrates are about 1/10 rate of phosphorylase a, so we reduce k1,k2,k3 by 10 to 5.72e-7, 1.4, 0.35 @@ -12714,46 +13161,46 @@ - PP1_active_925_0_ - CaMKII_thr286_p_CaM_845_0_ - Deph_thr286_cplx_928_0_ - Deph_thr286_927_0_ + PP1_active_898_0_ + CaMKII_thr286_p_CaM_818_0_ + Deph_thr286_cplx_901_0_ + Deph_thr286_900_0_ 1 588.235294118 - -212.048192771 + 212.048192771 cyan red - - + + - + - kinetics_479_0_ * ( k1 * PP1_active_925_0_*CaMKII_thr286_p_CaM_845_0_ - k2 * Deph_thr286_cplx_928_0_ ) + kinetics_451_0_ * ( k1 * PP1_active_898_0_*CaMKII_thr286_p_CaM_818_0_ - k2 * Deph_thr286_cplx_901_0_ ) - kinetics_479_0_ + kinetics_451_0_ k1 - PP1_active_925_0_ - CaMKII_thr286_p_CaM_845_0_ + PP1_active_898_0_ + CaMKII_thr286_p_CaM_818_0_ k2 - Deph_thr286_cplx_928_0_ + Deph_thr286_cplx_901_0_ @@ -12764,39 +13211,39 @@ - + - Deph_thr286_cplx_928_0_ - PP1_active_925_0_ - CaMKII_CaM_843_0_ - Deph_thr286_927_0_ + Deph_thr286_cplx_901_0_ + PP1_active_898_0_ + CaMKII_CaM_816_0_ + Deph_thr286_900_0_ 2 588.235294118 - -212.048192771 + 212.048192771 cyan red - + - - + + - kinetics_479_0_ * k3*Deph_thr286_cplx_928_0_ + kinetics_451_0_ * k3*Deph_thr286_cplx_901_0_ - kinetics_479_0_ + kinetics_451_0_ k3 - Deph_thr286_cplx_928_0_ + Deph_thr286_cplx_901_0_ @@ -12804,49 +13251,49 @@ - + - PP1_active_925_0_ - CaMKII_p_p_p_847_0_ - Deph_thr305_cplx_931_0_ - Deph_thr305_930_0_ + PP1_active_898_0_ + CaMKII_p_p_p_820_0_ + Deph_thr305_cplx_904_0_ + Deph_thr305_903_0_ 1 588.235294118 - -221.686746988 + 221.686746988 cyan red - - + + - + - kinetics_479_0_ * ( k1 * PP1_active_925_0_*CaMKII_p_p_p_847_0_ - k2 * Deph_thr305_cplx_931_0_ ) + kinetics_451_0_ * ( k1 * PP1_active_898_0_*CaMKII_p_p_p_820_0_ - k2 * Deph_thr305_cplx_904_0_ ) - kinetics_479_0_ + kinetics_451_0_ k1 - PP1_active_925_0_ - CaMKII_p_p_p_847_0_ + PP1_active_898_0_ + CaMKII_p_p_p_820_0_ k2 - Deph_thr305_cplx_931_0_ + Deph_thr305_cplx_904_0_ @@ -12857,39 +13304,39 @@ - + - Deph_thr305_cplx_931_0_ - PP1_active_925_0_ - CaMKII_thr286_849_0_ - Deph_thr305_930_0_ + Deph_thr305_cplx_904_0_ + PP1_active_898_0_ + CaMKII_thr286_822_0_ + Deph_thr305_903_0_ 2 588.235294118 - -221.686746988 + 221.686746988 cyan red - + - - + + - kinetics_479_0_ * k3*Deph_thr305_cplx_931_0_ + kinetics_451_0_ * k3*Deph_thr305_cplx_904_0_ - kinetics_479_0_ + kinetics_451_0_ k3 - Deph_thr305_cplx_931_0_ + Deph_thr305_cplx_904_0_ @@ -12897,7 +13344,7 @@ - + See Cohen et al @@ -12905,46 +13352,46 @@ - PP1_active_925_0_ - CaMKII_thr306_851_0_ - Deph_thr306_cplx_934_0_ - Deph_thr306_933_0_ + PP1_active_898_0_ + CaMKII_thr306_824_0_ + Deph_thr306_cplx_907_0_ + Deph_thr306_906_0_ 1 588.235294118 - -231.325301205 + 231.325301205 cyan red - - + + - + - kinetics_479_0_ * ( k1 * CaMKII_thr306_851_0_*PP1_active_925_0_ - k2 * Deph_thr306_cplx_934_0_ ) + kinetics_451_0_ * ( k1 * CaMKII_thr306_824_0_*PP1_active_898_0_ - k2 * Deph_thr306_cplx_907_0_ ) - kinetics_479_0_ + kinetics_451_0_ k1 - CaMKII_thr306_851_0_ - PP1_active_925_0_ + CaMKII_thr306_824_0_ + PP1_active_898_0_ k2 - Deph_thr306_cplx_934_0_ + Deph_thr306_cplx_907_0_ @@ -12955,39 +13402,39 @@ - + - Deph_thr306_cplx_934_0_ - PP1_active_925_0_ - CaMKII_841_0_ - Deph_thr306_933_0_ + Deph_thr306_cplx_907_0_ + PP1_active_898_0_ + CaMKII_814_0_ + Deph_thr306_906_0_ 2 588.235294118 - -231.325301205 + 231.325301205 cyan red - + - - + + - kinetics_479_0_ * k3*Deph_thr306_cplx_934_0_ + kinetics_451_0_ * k3*Deph_thr306_cplx_907_0_ - kinetics_479_0_ + kinetics_451_0_ k3 - Deph_thr306_cplx_934_0_ + Deph_thr306_cplx_907_0_ @@ -12995,49 +13442,49 @@ - + - PP1_active_925_0_ - CaMKII_p_p_p_847_0_ - Deph_thr286c_cplx_937_0_ - Deph_thr286c_936_0_ + PP1_active_898_0_ + CaMKII_p_p_p_820_0_ + Deph_thr286c_cplx_910_0_ + Deph_thr286c_909_0_ 1 588.235294118 - -240.963855422 + 240.963855422 cyan red - - + + - + - kinetics_479_0_ * ( k1 * PP1_active_925_0_*CaMKII_p_p_p_847_0_ - k2 * Deph_thr286c_cplx_937_0_ ) + kinetics_451_0_ * ( k1 * PP1_active_898_0_*CaMKII_p_p_p_820_0_ - k2 * Deph_thr286c_cplx_910_0_ ) - kinetics_479_0_ + kinetics_451_0_ k1 - PP1_active_925_0_ - CaMKII_p_p_p_847_0_ + PP1_active_898_0_ + CaMKII_p_p_p_820_0_ k2 - Deph_thr286c_cplx_937_0_ + Deph_thr286c_cplx_910_0_ @@ -13048,39 +13495,39 @@ - + - Deph_thr286c_cplx_937_0_ - PP1_active_925_0_ - CaMKII_thr306_851_0_ - Deph_thr286c_936_0_ + Deph_thr286c_cplx_910_0_ + PP1_active_898_0_ + CaMKII_thr306_824_0_ + Deph_thr286c_909_0_ 2 588.235294118 - -240.963855422 + 240.963855422 cyan red - + - - + + - kinetics_479_0_ * k3*Deph_thr286c_cplx_937_0_ + kinetics_451_0_ * k3*Deph_thr286c_cplx_910_0_ - kinetics_479_0_ + kinetics_451_0_ k3 - Deph_thr286c_cplx_937_0_ + Deph_thr286c_cplx_910_0_ @@ -13088,49 +13535,49 @@ - + - PP1_active_925_0_ - CaMKII_thr286_849_0_ - Deph_thr286b_cplx_940_0_ - Deph_thr286b_939_0_ + PP1_active_898_0_ + CaMKII_thr286_822_0_ + Deph_thr286b_cplx_913_0_ + Deph_thr286b_912_0_ 1 588.235294118 - -250.602409639 + 250.602409639 cyan red - - + + - + - kinetics_479_0_ * ( k1 * CaMKII_thr286_849_0_*PP1_active_925_0_ - k2 * Deph_thr286b_cplx_940_0_ ) + kinetics_451_0_ * ( k1 * PP1_active_898_0_*CaMKII_thr286_822_0_ - k2 * Deph_thr286b_cplx_913_0_ ) - kinetics_479_0_ + kinetics_451_0_ k1 - CaMKII_thr286_849_0_ - PP1_active_925_0_ + PP1_active_898_0_ + CaMKII_thr286_822_0_ k2 - Deph_thr286b_cplx_940_0_ + Deph_thr286b_cplx_913_0_ @@ -13141,39 +13588,39 @@ - + - Deph_thr286b_cplx_940_0_ - PP1_active_925_0_ - CaMKII_841_0_ - Deph_thr286b_939_0_ + Deph_thr286b_cplx_913_0_ + PP1_active_898_0_ + CaMKII_814_0_ + Deph_thr286b_912_0_ 2 588.235294118 - -250.602409639 + 250.602409639 cyan red - + - - + + - kinetics_479_0_ * k3*Deph_thr286b_cplx_940_0_ + kinetics_451_0_ * k3*Deph_thr286b_cplx_913_0_ - kinetics_479_0_ + kinetics_451_0_ k3 - Deph_thr286b_cplx_940_0_ + Deph_thr286b_cplx_913_0_ @@ -13181,7 +13628,7 @@ - + This pathway inhibits Ras when cAMP is elevated. See: Hordijk et al JBC 269:5 3534-3538 1994 Burgering et al EMBO J 12:11 4211-4220 1993 The rates are the same as used in PKA-phosph-I1 @@ -13189,46 +13636,46 @@ - PKA_active_978_0_ - inact_GEF_715_0_ - PKA_phosph_GEF_cplx_981_0_ - PKA_phosph_GEF_980_0_ + PKA_active_951_0_ + inact_GEF_688_0_ + PKA_phosph_GEF_cplx_954_0_ + PKA_phosph_GEF_953_0_ 1 882.352941176 - -212.048192771 + 212.048192771 yellow red - - + + - + - kinetics_479_0_ * ( k1 * PKA_active_978_0_*inact_GEF_715_0_ - k2 * PKA_phosph_GEF_cplx_981_0_ ) + kinetics_451_0_ * ( k1 * inact_GEF_688_0_*PKA_active_951_0_ - k2 * PKA_phosph_GEF_cplx_954_0_ ) - kinetics_479_0_ + kinetics_451_0_ k1 - PKA_active_978_0_ - inact_GEF_715_0_ + inact_GEF_688_0_ + PKA_active_951_0_ k2 - PKA_phosph_GEF_cplx_981_0_ + PKA_phosph_GEF_cplx_954_0_ @@ -13239,39 +13686,39 @@ - + - PKA_phosph_GEF_cplx_981_0_ - PKA_active_978_0_ - inact_GEF_p_736_0_ - PKA_phosph_GEF_980_0_ + PKA_phosph_GEF_cplx_954_0_ + PKA_active_951_0_ + inact_GEF_p_709_0_ + PKA_phosph_GEF_953_0_ 2 882.352941176 - -212.048192771 + 212.048192771 yellow red - + - - + + - kinetics_479_0_ * k3*PKA_phosph_GEF_cplx_981_0_ + kinetics_451_0_ * k3*PKA_phosph_GEF_cplx_954_0_ - kinetics_479_0_ + kinetics_451_0_ k3 - PKA_phosph_GEF_cplx_981_0_ + PKA_phosph_GEF_cplx_954_0_ @@ -13279,7 +13726,7 @@ - + #s from Bramson et al CRC crit rev Biochem 15:2 93-124. They have a huge list of peptide substrates and I have chosen high-ish rates. These consts give too much PKA activity, so lower Vmax 1/3. Now, k1 = 3e-5, k2 = 36, k3 = 9 (still pretty fast). Also lower Km 1/3 so k1 = 1e-5 Cohen et al FEBS Lett 76:182-86 1977 say rate =30% PKA act on phosphokinase beta. @@ -13287,46 +13734,46 @@ - PKA_active_978_0_ - I1_942_0_ - PKA_phosph_I1_cplx_984_0_ - PKA_phosph_I1_983_0_ + PKA_active_951_0_ + I1_915_0_ + PKA_phosph_I1_cplx_957_0_ + PKA_phosph_I1_956_0_ 1 882.352941176 - -221.686746988 + 221.686746988 yellow red - - + + - + - kinetics_479_0_ * ( k1 * PKA_active_978_0_*I1_942_0_ - k2 * PKA_phosph_I1_cplx_984_0_ ) + kinetics_451_0_ * ( k1 * I1_915_0_*PKA_active_951_0_ - k2 * PKA_phosph_I1_cplx_957_0_ ) - kinetics_479_0_ + kinetics_451_0_ k1 - PKA_active_978_0_ - I1_942_0_ + I1_915_0_ + PKA_active_951_0_ k2 - PKA_phosph_I1_cplx_984_0_ + PKA_phosph_I1_cplx_957_0_ @@ -13337,39 +13784,39 @@ - + - PKA_phosph_I1_cplx_984_0_ - PKA_active_978_0_ - I1_p_944_0_ - PKA_phosph_I1_983_0_ + PKA_phosph_I1_cplx_957_0_ + PKA_active_951_0_ + I1_p_917_0_ + PKA_phosph_I1_956_0_ 2 882.352941176 - -221.686746988 + 221.686746988 yellow red - + - - + + - kinetics_479_0_ * k3*PKA_phosph_I1_cplx_984_0_ + kinetics_451_0_ * k3*PKA_phosph_I1_cplx_957_0_ - kinetics_479_0_ + kinetics_451_0_ k3 - PKA_phosph_I1_cplx_984_0_ + PKA_phosph_I1_cplx_957_0_ @@ -13377,7 +13824,7 @@ - + Same rates as PKA-phosph-I1 @@ -13385,46 +13832,46 @@ - PKA_active_978_0_ - cAMP_PDE_1051_0_ - phosph_PDE_cplx_987_0_ - phosph_PDE_986_0_ + PKA_active_951_0_ + cAMP_PDE_1024_0_ + phosph_PDE_cplx_960_0_ + phosph_PDE_959_0_ 1 882.352941176 - -231.325301205 + 231.325301205 yellow red - - + + - + - kinetics_479_0_ * ( k1 * PKA_active_978_0_*cAMP_PDE_1051_0_ - k2 * phosph_PDE_cplx_987_0_ ) + kinetics_451_0_ * ( k1 * cAMP_PDE_1024_0_*PKA_active_951_0_ - k2 * phosph_PDE_cplx_960_0_ ) - kinetics_479_0_ + kinetics_451_0_ k1 - PKA_active_978_0_ - cAMP_PDE_1051_0_ + cAMP_PDE_1024_0_ + PKA_active_951_0_ k2 - phosph_PDE_cplx_987_0_ + phosph_PDE_cplx_960_0_ @@ -13435,39 +13882,39 @@ - + - phosph_PDE_cplx_987_0_ - PKA_active_978_0_ - cAMP_PDE_p_1056_0_ - phosph_PDE_986_0_ + phosph_PDE_cplx_960_0_ + PKA_active_951_0_ + cAMP_PDE_p_1029_0_ + phosph_PDE_959_0_ 2 882.352941176 - -231.325301205 + 231.325301205 yellow red - + - - + + - kinetics_479_0_ * k3*phosph_PDE_cplx_987_0_ + kinetics_451_0_ * k3*phosph_PDE_cplx_960_0_ - kinetics_479_0_ + kinetics_451_0_ k3 - phosph_PDE_cplx_987_0_ + phosph_PDE_cplx_960_0_ @@ -13475,46 +13922,46 @@ - + 29.4117647059 - -404.819277108 + 404.819277108 orange red - + - + - + - kinetics_479_0_ * ( kcat * ATP_1025_0_ * AC1_CaM_1027_0_ / ( Km + ATP_1025_0_)) + kinetics_451_0_ * ( kcat * ATP_998_0_ * AC1_CaM_1000_0_ / ( Km + ATP_998_0_)) - kinetics_479_0_ + kinetics_451_0_ kcat - ATP_1025_0_ - AC1_CaM_1027_0_ + ATP_998_0_ + AC1_CaM_1000_0_ Km - ATP_1025_0_ + ATP_998_0_ @@ -13525,7 +13972,7 @@ - + Reduced Km to match expt data for basal activation of AC2 by PKC. Now k1 = 2.9e-6, k2 = 72, k3 = 18 @@ -13534,42 +13981,42 @@ 58.8235294118 - -404.819277108 + 404.819277108 yellow red - + - + - + - kinetics_479_0_ * ( kcat * ATP_1025_0_ * AC2_p_1033_0_ / ( Km + ATP_1025_0_)) + kinetics_451_0_ * ( kcat * ATP_998_0_ * AC2_p_1006_0_ / ( Km + ATP_998_0_)) - kinetics_479_0_ + kinetics_451_0_ kcat - ATP_1025_0_ - AC2_p_1033_0_ + ATP_998_0_ + AC2_p_1006_0_ Km - ATP_1025_0_ + ATP_998_0_ @@ -13580,46 +14027,46 @@ - + 73.5294117647 - -404.819277108 + 404.819277108 yellow red - + - + - + - kinetics_479_0_ * ( kcat * ATP_1025_0_ * AC2_Gs_1037_0_ / ( Km + ATP_1025_0_)) + kinetics_451_0_ * ( kcat * ATP_998_0_ * AC2_Gs_1010_0_ / ( Km + ATP_998_0_)) - kinetics_479_0_ + kinetics_451_0_ kcat - ATP_1025_0_ - AC2_Gs_1037_0_ + ATP_998_0_ + AC2_Gs_1010_0_ Km - ATP_1025_0_ + ATP_998_0_ @@ -13630,46 +14077,46 @@ - + 102.941176471 - -404.819277108 + 404.819277108 orange red - + - + - + - kinetics_479_0_ * ( kcat * ATP_1025_0_ * AC1_Gs_1043_0_ / ( Km + ATP_1025_0_)) + kinetics_451_0_ * ( kcat * ATP_998_0_ * AC1_Gs_1016_0_ / ( Km + ATP_998_0_)) - kinetics_479_0_ + kinetics_451_0_ kcat - ATP_1025_0_ - AC1_Gs_1043_0_ + ATP_998_0_ + AC1_Gs_1016_0_ Km - ATP_1025_0_ + ATP_998_0_ @@ -13680,46 +14127,46 @@ - + 117.647058824 - -404.819277108 + 404.819277108 green red - + - + - + - kinetics_479_0_ * ( kcat * ATP_1025_0_ * AC2_p_Gs_1047_0_ / ( Km + ATP_1025_0_)) + kinetics_451_0_ * ( kcat * ATP_998_0_ * AC2_p_Gs_1020_0_ / ( Km + ATP_998_0_)) - kinetics_479_0_ + kinetics_451_0_ kcat - ATP_1025_0_ - AC2_p_Gs_1047_0_ + ATP_998_0_ + AC2_p_Gs_1020_0_ Km - ATP_1025_0_ + ATP_998_0_ @@ -13730,7 +14177,7 @@ - + Best rates are from Conti et al Biochem 34 7979-7987 1995. Though these are for the Sertoli cell form, it looks like they carry nicely into alternatively spliced brain form. See Sette et al JBC 269:28 18271-18274 Km ~2 uM, Vmax est ~ 10 umol/min/mg for pure form. Brain protein is 93 kD but this was 67. So k3 ~10, k2 ~40, k1 ~4.2e-6 @@ -13738,46 +14185,46 @@ - cAMP_PDE_1051_0_ - cAMP_1023_0_ - PDE_cplx_1054_0_ - PDE_1053_0_ + cAMP_PDE_1024_0_ + cAMP_996_0_ + PDE_cplx_1027_0_ + PDE_1026_0_ 1 7.35294117647 - -510.843373494 + 510.843373494 green red - - + + - + - kinetics_479_0_ * ( k1 * cAMP_PDE_1051_0_*cAMP_1023_0_ - k2 * PDE_cplx_1054_0_ ) + kinetics_451_0_ * ( k1 * cAMP_PDE_1024_0_*cAMP_996_0_ - k2 * PDE_cplx_1027_0_ ) - kinetics_479_0_ + kinetics_451_0_ k1 - cAMP_PDE_1051_0_ - cAMP_1023_0_ + cAMP_PDE_1024_0_ + cAMP_996_0_ k2 - PDE_cplx_1054_0_ + PDE_cplx_1027_0_ @@ -13788,39 +14235,39 @@ - + - PDE_cplx_1054_0_ - cAMP_PDE_1051_0_ - AMP_1085_0_ - PDE_1053_0_ + PDE_cplx_1027_0_ + cAMP_PDE_1024_0_ + AMP_1058_0_ + PDE_1026_0_ 2 7.35294117647 - -510.843373494 + 510.843373494 green red - + - - + + - kinetics_479_0_ * k3*PDE_cplx_1054_0_ + kinetics_451_0_ * k3*PDE_cplx_1027_0_ - kinetics_479_0_ + kinetics_451_0_ k3 - PDE_cplx_1054_0_ + PDE_cplx_1027_0_ @@ -13828,7 +14275,7 @@ - + This form has about twice the activity of the unphosphorylated form. See Sette et al JBC 269:28 18271-18274 1994. We'll ignore cGMP effects for now. @@ -13836,46 +14283,46 @@ - cAMP_PDE_p_1056_0_ - cAMP_1023_0_ - PDE_p_cplx_1059_0_ - PDE_p_1058_0_ + cAMP_PDE_p_1029_0_ + cAMP_996_0_ + PDE_p_cplx_1032_0_ + PDE_p_1031_0_ 1 22.0588235294 - -510.843373494 + 510.843373494 green red - - + + - + - kinetics_479_0_ * ( k1 * cAMP_PDE_p_1056_0_*cAMP_1023_0_ - k2 * PDE_p_cplx_1059_0_ ) + kinetics_451_0_ * ( k1 * cAMP_996_0_*cAMP_PDE_p_1029_0_ - k2 * PDE_p_cplx_1032_0_ ) - kinetics_479_0_ + kinetics_451_0_ k1 - cAMP_PDE_p_1056_0_ - cAMP_1023_0_ + cAMP_996_0_ + cAMP_PDE_p_1029_0_ k2 - PDE_p_cplx_1059_0_ + PDE_p_cplx_1032_0_ @@ -13886,39 +14333,39 @@ - + - PDE_p_cplx_1059_0_ - cAMP_PDE_p_1056_0_ - AMP_1085_0_ - PDE_p_1058_0_ + PDE_p_cplx_1032_0_ + cAMP_PDE_p_1029_0_ + AMP_1058_0_ + PDE_p_1031_0_ 2 22.0588235294 - -510.843373494 + 510.843373494 green red - + - - + + - kinetics_479_0_ * k3*PDE_p_cplx_1059_0_ + kinetics_451_0_ * k3*PDE_p_cplx_1032_0_ - kinetics_479_0_ + kinetics_451_0_ k3 - PDE_p_cplx_1059_0_ + PDE_p_cplx_1032_0_ @@ -13926,7 +14373,7 @@ - + Rate is 1/6 of the CaM stim form. We'll just reduce all lf k1, k2, k3 so that the Vmax goes down 1/6. @@ -13934,46 +14381,46 @@ - PDE1_1061_0_ - cAMP_1023_0_ - PDE1_cplx_1064_0_ - PDE1_1063_0_ + PDE1_1034_0_ + cAMP_996_0_ + PDE1_cplx_1037_0_ + PDE1_1036_0_ 1 36.7647058824 - -510.843373494 + 510.843373494 green red - - + + - + - kinetics_479_0_ * ( k1 * PDE1_1061_0_*cAMP_1023_0_ - k2 * PDE1_cplx_1064_0_ ) + kinetics_451_0_ * ( k1 * PDE1_1034_0_*cAMP_996_0_ - k2 * PDE1_cplx_1037_0_ ) - kinetics_479_0_ + kinetics_451_0_ k1 - PDE1_1061_0_ - cAMP_1023_0_ + PDE1_1034_0_ + cAMP_996_0_ k2 - PDE1_cplx_1064_0_ + PDE1_cplx_1037_0_ @@ -13984,39 +14431,39 @@ - + - PDE1_cplx_1064_0_ - PDE1_1061_0_ - AMP_1085_0_ - PDE1_1063_0_ + PDE1_cplx_1037_0_ + PDE1_1034_0_ + AMP_1058_0_ + PDE1_1036_0_ 2 36.7647058824 - -510.843373494 + 510.843373494 green red - + - - + + - kinetics_479_0_ * k3*PDE1_cplx_1064_0_ + kinetics_451_0_ * k3*PDE1_cplx_1037_0_ - kinetics_479_0_ + kinetics_451_0_ k3 - PDE1_cplx_1064_0_ + PDE1_cplx_1037_0_ @@ -14024,7 +14471,7 @@ - + Max activity ~10umol/min/mg in presence of lots of CaM. Affinity is low, 40 uM. k3 = 10, k2 = 40, k1 = (50/40) / 6e5. @@ -14032,46 +14479,46 @@ - CaM_dot_PDE1_1066_0_ - cAMP_1023_0_ - CaM_dot_PDE1_cplx_1069_0_ - CaM_dot_PDE1_1068_0_ + CaM_dot_PDE1_1039_0_ + cAMP_996_0_ + CaM_dot_PDE1_cplx_1042_0_ + CaM_dot_PDE1_1041_0_ 1 51.4705882353 - -510.843373494 + 510.843373494 green red - - + + - + - kinetics_479_0_ * ( k1 * CaM_dot_PDE1_1066_0_*cAMP_1023_0_ - k2 * CaM_dot_PDE1_cplx_1069_0_ ) + kinetics_451_0_ * ( k1 * cAMP_996_0_*CaM_dot_PDE1_1039_0_ - k2 * CaM_dot_PDE1_cplx_1042_0_ ) - kinetics_479_0_ + kinetics_451_0_ k1 - CaM_dot_PDE1_1066_0_ - cAMP_1023_0_ + cAMP_996_0_ + CaM_dot_PDE1_1039_0_ k2 - CaM_dot_PDE1_cplx_1069_0_ + CaM_dot_PDE1_cplx_1042_0_ @@ -14082,39 +14529,39 @@ - + - CaM_dot_PDE1_cplx_1069_0_ - CaM_dot_PDE1_1066_0_ - AMP_1085_0_ - CaM_dot_PDE1_1068_0_ + CaM_dot_PDE1_cplx_1042_0_ + CaM_dot_PDE1_1039_0_ + AMP_1058_0_ + CaM_dot_PDE1_1041_0_ 2 51.4705882353 - -510.843373494 + 510.843373494 green red - + - - + + - kinetics_479_0_ * k3*CaM_dot_PDE1_cplx_1069_0_ + kinetics_451_0_ * k3*CaM_dot_PDE1_cplx_1042_0_ - kinetics_479_0_ + kinetics_451_0_ k3 - CaM_dot_PDE1_cplx_1069_0_ + CaM_dot_PDE1_cplx_1042_0_ @@ -14122,7 +14569,7 @@ - + The original kinetics have been modified to obey the k2 = 4 * k3 rule, while keeping kcat and Km fixed. As noted in the NOTES, the only constraining data point is the time course of MAPK dephosphorylation, which this model satisfies. It would be nice to have more accurate estimates of rate consts and MKP-1 levels from the literature. Effective Km : 67 nM kcat = 1.43 umol/min/mg @@ -14130,46 +14577,46 @@ - MKP_1_1129_0_ - MAPK_p_684_0_ - MKP1_tyr_deph_cplx_1132_0_ - MKP1_tyr_deph_1131_0_ + MKP_1_1102_0_ + MAPK_p_657_0_ + MKP1_tyr_deph_cplx_1105_0_ + MKP1_tyr_deph_1104_0_ 1 441.176470588 - -404.819277108 + 404.819277108 hotpink red - - + + - + - kinetics_479_0_ * ( k1 * MKP_1_1129_0_*MAPK_p_684_0_ - k2 * MKP1_tyr_deph_cplx_1132_0_ ) + kinetics_451_0_ * ( k1 * MAPK_p_657_0_*MKP_1_1102_0_ - k2 * MKP1_tyr_deph_cplx_1105_0_ ) - kinetics_479_0_ + kinetics_451_0_ k1 - MKP_1_1129_0_ - MAPK_p_684_0_ + MAPK_p_657_0_ + MKP_1_1102_0_ k2 - MKP1_tyr_deph_cplx_1132_0_ + MKP1_tyr_deph_cplx_1105_0_ @@ -14180,39 +14627,39 @@ - + - MKP1_tyr_deph_cplx_1132_0_ - MKP_1_1129_0_ - MAPK_680_0_ - MKP1_tyr_deph_1131_0_ + MKP1_tyr_deph_cplx_1105_0_ + MKP_1_1102_0_ + MAPK_653_0_ + MKP1_tyr_deph_1104_0_ 2 441.176470588 - -404.819277108 + 404.819277108 hotpink red - + - - + + - kinetics_479_0_ * k3*MKP1_tyr_deph_cplx_1132_0_ + kinetics_451_0_ * k3*MKP1_tyr_deph_cplx_1105_0_ - kinetics_479_0_ + kinetics_451_0_ k3 - MKP1_tyr_deph_cplx_1132_0_ + MKP1_tyr_deph_cplx_1105_0_ @@ -14220,7 +14667,7 @@ - + See MKP1-tyr-deph @@ -14228,46 +14675,46 @@ - MKP_1_1129_0_ - MAPK_p_p_648_0_ - MKP1_thr_deph_cplx_1135_0_ - MKP1_thr_deph_1134_0_ + MKP_1_1102_0_ + MAPK_p_p_621_0_ + MKP1_thr_deph_cplx_1108_0_ + MKP1_thr_deph_1107_0_ 1 441.176470588 - -414.457831325 + 414.457831325 hotpink red - - + + - + - kinetics_479_0_ * ( k1 * MAPK_p_p_648_0_*MKP_1_1129_0_ - k2 * MKP1_thr_deph_cplx_1135_0_ ) + kinetics_451_0_ * ( k1 * MAPK_p_p_621_0_*MKP_1_1102_0_ - k2 * MKP1_thr_deph_cplx_1108_0_ ) - kinetics_479_0_ + kinetics_451_0_ k1 - MAPK_p_p_648_0_ - MKP_1_1129_0_ + MAPK_p_p_621_0_ + MKP_1_1102_0_ k2 - MKP1_thr_deph_cplx_1135_0_ + MKP1_thr_deph_cplx_1108_0_ @@ -14278,39 +14725,39 @@ - + - MKP1_thr_deph_cplx_1135_0_ - MKP_1_1129_0_ - MAPK_p_684_0_ - MKP1_thr_deph_1134_0_ + MKP1_thr_deph_cplx_1108_0_ + MKP_1_1102_0_ + MAPK_p_657_0_ + MKP1_thr_deph_1107_0_ 2 441.176470588 - -414.457831325 + 414.457831325 hotpink red - + - - + + - kinetics_479_0_ * k3*MKP1_thr_deph_cplx_1135_0_ + kinetics_451_0_ * k3*MKP1_thr_deph_cplx_1108_0_ - kinetics_479_0_ + kinetics_451_0_ k3 - MKP1_thr_deph_cplx_1135_0_ + MKP1_thr_deph_cplx_1108_0_ @@ -14318,7 +14765,7 @@ - + See parent PPhosphatase2A for parms @@ -14326,46 +14773,46 @@ - PPhosphatase2A_1137_0_ - craf_1_p_670_0_ - craf_dephospho_cplx_1140_0_ - craf_dephospho_1139_0_ + PPhosphatase2A_1110_0_ + craf_1_p_643_0_ + craf_dephospho_cplx_1113_0_ + craf_dephospho_1112_0_ 1 455.882352941 - -404.819277108 + 404.819277108 hotpink red - - + + - + - kinetics_479_0_ * ( k1 * PPhosphatase2A_1137_0_*craf_1_p_670_0_ - k2 * craf_dephospho_cplx_1140_0_ ) + kinetics_451_0_ * ( k1 * craf_1_p_643_0_*PPhosphatase2A_1110_0_ - k2 * craf_dephospho_cplx_1113_0_ ) - kinetics_479_0_ + kinetics_451_0_ k1 - PPhosphatase2A_1137_0_ - craf_1_p_670_0_ + craf_1_p_643_0_ + PPhosphatase2A_1110_0_ k2 - craf_dephospho_cplx_1140_0_ + craf_dephospho_cplx_1113_0_ @@ -14376,39 +14823,39 @@ - + - craf_dephospho_cplx_1140_0_ - PPhosphatase2A_1137_0_ - craf_1_668_0_ - craf_dephospho_1139_0_ + craf_dephospho_cplx_1113_0_ + PPhosphatase2A_1110_0_ + craf_1_641_0_ + craf_dephospho_1112_0_ 2 455.882352941 - -404.819277108 + 404.819277108 hotpink red - + - - + + - kinetics_479_0_ * k3*craf_dephospho_cplx_1140_0_ + kinetics_451_0_ * k3*craf_dephospho_cplx_1113_0_ - kinetics_479_0_ + kinetics_451_0_ k3 - craf_dephospho_cplx_1140_0_ + craf_dephospho_cplx_1113_0_ @@ -14416,7 +14863,7 @@ - + See: Kyriakis et al Nature 358 pp 417-421 1992 Ahn et al Curr Op Cell Biol 4:992-999 1992 for this pathway. See parent PPhosphatase2A for parms. @@ -14424,46 +14871,46 @@ - PPhosphatase2A_1137_0_ - MAPKK_p_p_686_0_ - MAPKK_dephospho_cplx_1143_0_ - MAPKK_dephospho_1142_0_ + PPhosphatase2A_1110_0_ + MAPKK_p_p_659_0_ + MAPKK_dephospho_cplx_1116_0_ + MAPKK_dephospho_1115_0_ 1 455.882352941 - -414.457831325 + 414.457831325 hotpink red - - + + - + - kinetics_479_0_ * ( k1 * PPhosphatase2A_1137_0_*MAPKK_p_p_686_0_ - k2 * MAPKK_dephospho_cplx_1143_0_ ) + kinetics_451_0_ * ( k1 * MAPKK_p_p_659_0_*PPhosphatase2A_1110_0_ - k2 * MAPKK_dephospho_cplx_1116_0_ ) - kinetics_479_0_ + kinetics_451_0_ k1 - PPhosphatase2A_1137_0_ - MAPKK_p_p_686_0_ + MAPKK_p_p_659_0_ + PPhosphatase2A_1110_0_ k2 - MAPKK_dephospho_cplx_1143_0_ + MAPKK_dephospho_cplx_1116_0_ @@ -14474,39 +14921,39 @@ - + - MAPKK_dephospho_cplx_1143_0_ - PPhosphatase2A_1137_0_ - MAPKK_p_694_0_ - MAPKK_dephospho_1142_0_ + MAPKK_dephospho_cplx_1116_0_ + PPhosphatase2A_1110_0_ + MAPKK_p_667_0_ + MAPKK_dephospho_1115_0_ 2 455.882352941 - -414.457831325 + 414.457831325 hotpink red - + - - + + - kinetics_479_0_ * k3*MAPKK_dephospho_cplx_1143_0_ + kinetics_451_0_ * k3*MAPKK_dephospho_cplx_1116_0_ - kinetics_479_0_ + kinetics_451_0_ k3 - MAPKK_dephospho_cplx_1143_0_ + MAPKK_dephospho_cplx_1116_0_ @@ -14514,49 +14961,49 @@ - + - PPhosphatase2A_1137_0_ - MAPKK_p_694_0_ - MAPKK_dephospho_ser_cplx_1146_0_ - MAPKK_dephospho_ser_1145_0_ + PPhosphatase2A_1110_0_ + MAPKK_p_667_0_ + MAPKK_dephospho_ser_cplx_1119_0_ + MAPKK_dephospho_ser_1118_0_ 1 455.882352941 - -424.096385542 + 424.096385542 hotpink red - - + + - + - kinetics_479_0_ * ( k1 * PPhosphatase2A_1137_0_*MAPKK_p_694_0_ - k2 * MAPKK_dephospho_ser_cplx_1146_0_ ) + kinetics_451_0_ * ( k1 * MAPKK_p_667_0_*PPhosphatase2A_1110_0_ - k2 * MAPKK_dephospho_ser_cplx_1119_0_ ) - kinetics_479_0_ + kinetics_451_0_ k1 - PPhosphatase2A_1137_0_ - MAPKK_p_694_0_ + MAPKK_p_667_0_ + PPhosphatase2A_1110_0_ k2 - MAPKK_dephospho_ser_cplx_1146_0_ + MAPKK_dephospho_ser_cplx_1119_0_ @@ -14567,39 +15014,39 @@ - + - MAPKK_dephospho_ser_cplx_1146_0_ - PPhosphatase2A_1137_0_ - MAPKK_678_0_ - MAPKK_dephospho_ser_1145_0_ + MAPKK_dephospho_ser_cplx_1119_0_ + PPhosphatase2A_1110_0_ + MAPKK_651_0_ + MAPKK_dephospho_ser_1118_0_ 2 455.882352941 - -424.096385542 + 424.096385542 hotpink red - + - - + + - kinetics_479_0_ * k3*MAPKK_dephospho_ser_cplx_1146_0_ + kinetics_451_0_ * k3*MAPKK_dephospho_ser_cplx_1119_0_ - kinetics_479_0_ + kinetics_451_0_ k3 - MAPKK_dephospho_ser_cplx_1146_0_ + MAPKK_dephospho_ser_cplx_1119_0_ @@ -14607,7 +15054,7 @@ - + Ueki et al JBC 269(22) pp 15756-15761 1994 show hyperphosphorylation of craf, so this is there to dephosphorylate it. Identity of phosphatase is not known to me, but it may be PP2A like the rest, so I have made it so. @@ -14615,46 +15062,46 @@ - PPhosphatase2A_1137_0_ - craf_1_p_p_682_0_ - craf_p_p_dephospho_cplx_1149_0_ - craf_p_p_dephospho_1148_0_ + PPhosphatase2A_1110_0_ + craf_1_p_p_655_0_ + craf_p_p_dephospho_cplx_1122_0_ + craf_p_p_dephospho_1121_0_ 1 455.882352941 - -433.734939759 + 433.734939759 hotpink red - - + + - + - kinetics_479_0_ * ( k1 * PPhosphatase2A_1137_0_*craf_1_p_p_682_0_ - k2 * craf_p_p_dephospho_cplx_1149_0_ ) + kinetics_451_0_ * ( k1 * PPhosphatase2A_1110_0_*craf_1_p_p_655_0_ - k2 * craf_p_p_dephospho_cplx_1122_0_ ) - kinetics_479_0_ + kinetics_451_0_ k1 - PPhosphatase2A_1137_0_ - craf_1_p_p_682_0_ + PPhosphatase2A_1110_0_ + craf_1_p_p_655_0_ k2 - craf_p_p_dephospho_cplx_1149_0_ + craf_p_p_dephospho_cplx_1122_0_ @@ -14665,39 +15112,39 @@ - + - craf_p_p_dephospho_cplx_1149_0_ - PPhosphatase2A_1137_0_ - craf_1_p_670_0_ - craf_p_p_dephospho_1148_0_ + craf_p_p_dephospho_cplx_1122_0_ + PPhosphatase2A_1110_0_ + craf_1_p_643_0_ + craf_p_p_dephospho_1121_0_ 2 455.882352941 - -433.734939759 + 433.734939759 hotpink red - + - - + + - kinetics_479_0_ * k3*craf_p_p_dephospho_cplx_1149_0_ + kinetics_451_0_ * k3*craf_p_p_dephospho_cplx_1122_0_ - kinetics_479_0_ + kinetics_451_0_ k3 - craf_p_p_dephospho_cplx_1149_0_ + craf_p_p_dephospho_cplx_1122_0_ @@ -14705,49 +15152,49 @@ - + - PPhosphatase2A_1137_0_ - craf_1_p_ser259_704_0_ - deph_raf_ser259_cplx_1152_0_ - deph_raf_ser259_1151_0_ + PPhosphatase2A_1110_0_ + craf_1_p_ser259_677_0_ + deph_raf_ser259_cplx_1125_0_ + deph_raf_ser259_1124_0_ 1 455.882352941 - -395.180722892 + 395.180722892 red hotpink - - + + - + - kinetics_479_0_ * ( k1 * craf_1_p_ser259_704_0_*PPhosphatase2A_1137_0_ - k2 * deph_raf_ser259_cplx_1152_0_ ) + kinetics_451_0_ * ( k1 * craf_1_p_ser259_677_0_*PPhosphatase2A_1110_0_ - k2 * deph_raf_ser259_cplx_1125_0_ ) - kinetics_479_0_ + kinetics_451_0_ k1 - craf_1_p_ser259_704_0_ - PPhosphatase2A_1137_0_ + craf_1_p_ser259_677_0_ + PPhosphatase2A_1110_0_ k2 - deph_raf_ser259_cplx_1152_0_ + deph_raf_ser259_cplx_1125_0_ @@ -14758,39 +15205,39 @@ - + - deph_raf_ser259_cplx_1152_0_ - PPhosphatase2A_1137_0_ - craf_1_668_0_ - deph_raf_ser259_1151_0_ + deph_raf_ser259_cplx_1125_0_ + PPhosphatase2A_1110_0_ + craf_1_641_0_ + deph_raf_ser259_1124_0_ 2 455.882352941 - -395.180722892 + 395.180722892 red hotpink - + - - + + - kinetics_479_0_ * k3*deph_raf_ser259_cplx_1152_0_ + kinetics_451_0_ * k3*deph_raf_ser259_cplx_1125_0_ - kinetics_479_0_ + kinetics_451_0_ k3 - deph_raf_ser259_cplx_1152_0_ + deph_raf_ser259_cplx_1125_0_ @@ -14798,7 +15245,7 @@ - + PP2A does most of the dephosph of I1 at basal Ca levels. See the review by Cohen in Ann Rev Biochem 1989. For now, lets halve Km. k1 was 3.3e-6, now 6.6e-6 @@ -14806,46 +15253,46 @@ - PP2A_1154_0_ - I1_p_944_0_ - PP2A_dephospho_I1_cplx_1157_0_ - PP2A_dephospho_I1_1156_0_ + PP2A_1127_0_ + I1_p_917_0_ + PP2A_dephospho_I1_cplx_1130_0_ + PP2A_dephospho_I1_1129_0_ 1 470.588235294 - -404.819277108 + 404.819277108 red red - - + + - + - kinetics_479_0_ * ( k1 * I1_p_944_0_*PP2A_1154_0_ - k2 * PP2A_dephospho_I1_cplx_1157_0_ ) + kinetics_451_0_ * ( k1 * I1_p_917_0_*PP2A_1127_0_ - k2 * PP2A_dephospho_I1_cplx_1130_0_ ) - kinetics_479_0_ + kinetics_451_0_ k1 - I1_p_944_0_ - PP2A_1154_0_ + I1_p_917_0_ + PP2A_1127_0_ k2 - PP2A_dephospho_I1_cplx_1157_0_ + PP2A_dephospho_I1_cplx_1130_0_ @@ -14856,39 +15303,39 @@ - + - PP2A_dephospho_I1_cplx_1157_0_ - PP2A_1154_0_ - I1_942_0_ - PP2A_dephospho_I1_1156_0_ + PP2A_dephospho_I1_cplx_1130_0_ + PP2A_1127_0_ + I1_915_0_ + PP2A_dephospho_I1_1129_0_ 2 470.588235294 - -404.819277108 + 404.819277108 red red - + - - + + - kinetics_479_0_ * k3*PP2A_dephospho_I1_cplx_1157_0_ + kinetics_451_0_ * k3*PP2A_dephospho_I1_cplx_1130_0_ - kinetics_479_0_ + kinetics_451_0_ k3 - PP2A_dephospho_I1_cplx_1157_0_ + PP2A_dephospho_I1_cplx_1130_0_ @@ -14896,7 +15343,7 @@ - + k1 changed from 3.3e-6 to 6.6e-6 @@ -14904,46 +15351,46 @@ - PP2A_1154_0_ - PP1_I1_p_946_0_ - PP2A_dephospho_PP1_I_p_cplx_1160_0_ - PP2A_dephospho_PP1_I_p_1159_0_ + PP2A_1127_0_ + PP1_I1_p_919_0_ + PP2A_dephospho_PP1_I_p_cplx_1133_0_ + PP2A_dephospho_PP1_I_p_1132_0_ 1 470.588235294 - -414.457831325 + 414.457831325 red red - - + + - + - kinetics_479_0_ * ( k1 * PP2A_1154_0_*PP1_I1_p_946_0_ - k2 * PP2A_dephospho_PP1_I_p_cplx_1160_0_ ) + kinetics_451_0_ * ( k1 * PP1_I1_p_919_0_*PP2A_1127_0_ - k2 * PP2A_dephospho_PP1_I_p_cplx_1133_0_ ) - kinetics_479_0_ + kinetics_451_0_ k1 - PP2A_1154_0_ - PP1_I1_p_946_0_ + PP1_I1_p_919_0_ + PP2A_1127_0_ k2 - PP2A_dephospho_PP1_I_p_cplx_1160_0_ + PP2A_dephospho_PP1_I_p_cplx_1133_0_ @@ -14954,39 +15401,39 @@ - + - PP2A_dephospho_PP1_I_p_cplx_1160_0_ - PP2A_1154_0_ - PP1_I1_948_0_ - PP2A_dephospho_PP1_I_p_1159_0_ + PP2A_dephospho_PP1_I_p_cplx_1133_0_ + PP2A_1127_0_ + PP1_I1_921_0_ + PP2A_dephospho_PP1_I_p_1132_0_ 2 470.588235294 - -414.457831325 + 414.457831325 red red - + - - + + - kinetics_479_0_ * k3*PP2A_dephospho_PP1_I_p_cplx_1160_0_ + kinetics_451_0_ * k3*PP2A_dephospho_PP1_I_p_cplx_1133_0_ - kinetics_479_0_ + kinetics_451_0_ k3 - PP2A_dephospho_PP1_I_p_cplx_1160_0_ + PP2A_dephospho_PP1_I_p_cplx_1133_0_ @@ -14994,49 +15441,49 @@ - + - PP2A_1154_0_ - S6K_p_1327_0_ - dephos_clus_S6K_cplx_1163_0_ - dephos_clus_S6K_1162_0_ + PP2A_1127_0_ + S6K_p_1300_0_ + dephos_clus_S6K_cplx_1136_0_ + dephos_clus_S6K_1135_0_ 1 470.588235294 - -424.096385542 + 424.096385542 red 25 - - + + - + - kinetics_479_0_ * ( k1 * PP2A_1154_0_*S6K_p_1327_0_ - k2 * dephos_clus_S6K_cplx_1163_0_ ) + kinetics_451_0_ * ( k1 * S6K_p_1300_0_*PP2A_1127_0_ - k2 * dephos_clus_S6K_cplx_1136_0_ ) - kinetics_479_0_ + kinetics_451_0_ k1 - PP2A_1154_0_ - S6K_p_1327_0_ + S6K_p_1300_0_ + PP2A_1127_0_ k2 - dephos_clus_S6K_cplx_1163_0_ + dephos_clus_S6K_cplx_1136_0_ @@ -15047,39 +15494,39 @@ - + - dephos_clus_S6K_cplx_1163_0_ - PP2A_1154_0_ - S6K_1329_0_ - dephos_clus_S6K_1162_0_ + dephos_clus_S6K_cplx_1136_0_ + PP2A_1127_0_ + S6K_1302_0_ + dephos_clus_S6K_1135_0_ 2 470.588235294 - -424.096385542 + 424.096385542 red 25 - + - - + + - kinetics_479_0_ * k3*dephos_clus_S6K_cplx_1163_0_ + kinetics_451_0_ * k3*dephos_clus_S6K_cplx_1136_0_ - kinetics_479_0_ + kinetics_451_0_ k3 - dephos_clus_S6K_cplx_1163_0_ + dephos_clus_S6K_cplx_1136_0_ @@ -15087,49 +15534,49 @@ - + - PP2A_1154_0_ - S6K_thr_412_1331_0_ - dephos_S6K_cplx_1166_0_ - dephos_S6K_1165_0_ + PP2A_1127_0_ + S6K_thr_412_1304_0_ + dephos_S6K_cplx_1139_0_ + dephos_S6K_1138_0_ 1 470.588235294 - -433.734939759 + 433.734939759 red 25 - - + + - + - kinetics_479_0_ * ( k1 * PP2A_1154_0_*S6K_thr_412_1331_0_ - k2 * dephos_S6K_cplx_1166_0_ ) + kinetics_451_0_ * ( k1 * S6K_thr_412_1304_0_*PP2A_1127_0_ - k2 * dephos_S6K_cplx_1139_0_ ) - kinetics_479_0_ + kinetics_451_0_ k1 - PP2A_1154_0_ - S6K_thr_412_1331_0_ + S6K_thr_412_1304_0_ + PP2A_1127_0_ k2 - dephos_S6K_cplx_1166_0_ + dephos_S6K_cplx_1139_0_ @@ -15140,39 +15587,39 @@ - + - dephos_S6K_cplx_1166_0_ - PP2A_1154_0_ - S6K_p_1327_0_ - dephos_S6K_1165_0_ + dephos_S6K_cplx_1139_0_ + PP2A_1127_0_ + S6K_p_1300_0_ + dephos_S6K_1138_0_ 2 470.588235294 - -433.734939759 + 433.734939759 red 25 - + - - + + - kinetics_479_0_ * k3*dephos_S6K_cplx_1166_0_ + kinetics_451_0_ * k3*dephos_S6K_cplx_1139_0_ - kinetics_479_0_ + kinetics_451_0_ k3 - dephos_S6K_cplx_1166_0_ + dephos_S6K_cplx_1139_0_ @@ -15180,49 +15627,49 @@ - + - PP2A_1154_0_ - S6K_thr_252_1336_0_ - dephosp_S6K_cplx_1169_0_ - dephosp_S6K_1168_0_ + PP2A_1127_0_ + S6K_thr_252_1309_0_ + dephosp_S6K_cplx_1142_0_ + dephosp_S6K_1141_0_ 1 470.588235294 - -443.373493976 + 443.373493976 red 25 - - + + - + - kinetics_479_0_ * ( k1 * S6K_thr_252_1336_0_*PP2A_1154_0_ - k2 * dephosp_S6K_cplx_1169_0_ ) + kinetics_451_0_ * ( k1 * S6K_thr_252_1309_0_*PP2A_1127_0_ - k2 * dephosp_S6K_cplx_1142_0_ ) - kinetics_479_0_ + kinetics_451_0_ k1 - S6K_thr_252_1336_0_ - PP2A_1154_0_ + S6K_thr_252_1309_0_ + PP2A_1127_0_ k2 - dephosp_S6K_cplx_1169_0_ + dephosp_S6K_cplx_1142_0_ @@ -15233,39 +15680,39 @@ - + - dephosp_S6K_cplx_1169_0_ - PP2A_1154_0_ - S6K_thr_412_1331_0_ - dephosp_S6K_1168_0_ + dephosp_S6K_cplx_1142_0_ + PP2A_1127_0_ + S6K_thr_412_1304_0_ + dephosp_S6K_1141_0_ 2 470.588235294 - -443.373493976 + 443.373493976 red 25 - + - - + + - kinetics_479_0_ * k3*dephosp_S6K_cplx_1169_0_ + kinetics_451_0_ * k3*dephosp_S6K_cplx_1142_0_ - kinetics_479_0_ + kinetics_451_0_ k3 - dephosp_S6K_cplx_1169_0_ + dephosp_S6K_cplx_1142_0_ @@ -15273,49 +15720,49 @@ - + - PP2A_1154_0_ - PIP3_AKT_t308_s473_1260_0_ - Dephos_AKTser473_cplx_1172_0_ - Dephos_AKTser473_1171_0_ + PP2A_1127_0_ + PIP3_AKT_t308_s473_1233_0_ + Dephos_AKTser473_cplx_1145_0_ + Dephos_AKTser473_1144_0_ 1 470.588235294 - -453.012048193 + 453.012048193 red 46 - - + + - + - kinetics_479_0_ * ( k1 * PP2A_1154_0_*PIP3_AKT_t308_s473_1260_0_ - k2 * Dephos_AKTser473_cplx_1172_0_ ) + kinetics_451_0_ * ( k1 * PIP3_AKT_t308_s473_1233_0_*PP2A_1127_0_ - k2 * Dephos_AKTser473_cplx_1145_0_ ) - kinetics_479_0_ + kinetics_451_0_ k1 - PP2A_1154_0_ - PIP3_AKT_t308_s473_1260_0_ + PIP3_AKT_t308_s473_1233_0_ + PP2A_1127_0_ k2 - Dephos_AKTser473_cplx_1172_0_ + Dephos_AKTser473_cplx_1145_0_ @@ -15326,39 +15773,39 @@ - + - Dephos_AKTser473_cplx_1172_0_ - PP2A_1154_0_ - PIP3_AKT_thr308_1258_0_ - Dephos_AKTser473_1171_0_ + Dephos_AKTser473_cplx_1145_0_ + PP2A_1127_0_ + PIP3_AKT_thr308_1231_0_ + Dephos_AKTser473_1144_0_ 2 470.588235294 - -453.012048193 + 453.012048193 red 46 - + - - + + - kinetics_479_0_ * k3*Dephos_AKTser473_cplx_1172_0_ + kinetics_451_0_ * k3*Dephos_AKTser473_cplx_1145_0_ - kinetics_479_0_ + kinetics_451_0_ k3 - Dephos_AKTser473_cplx_1172_0_ + Dephos_AKTser473_cplx_1145_0_ @@ -15366,49 +15813,49 @@ - + - PP2A_1154_0_ - PIP3_AKT_thr308_1258_0_ - Dephosph_AKTthr308_cplx_1175_0_ - Dephosph_AKTthr308_1174_0_ + PP2A_1127_0_ + PIP3_AKT_thr308_1231_0_ + Dephosph_AKTthr308_cplx_1148_0_ + Dephosph_AKTthr308_1147_0_ 1 470.588235294 - -462.65060241 + 462.65060241 red 46 - - + + - + - kinetics_479_0_ * ( k1 * PP2A_1154_0_*PIP3_AKT_thr308_1258_0_ - k2 * Dephosph_AKTthr308_cplx_1175_0_ ) + kinetics_451_0_ * ( k1 * PIP3_AKT_thr308_1231_0_*PP2A_1127_0_ - k2 * Dephosph_AKTthr308_cplx_1148_0_ ) - kinetics_479_0_ + kinetics_451_0_ k1 - PP2A_1154_0_ - PIP3_AKT_thr308_1258_0_ + PIP3_AKT_thr308_1231_0_ + PP2A_1127_0_ k2 - Dephosph_AKTthr308_cplx_1175_0_ + Dephosph_AKTthr308_cplx_1148_0_ @@ -15419,39 +15866,39 @@ - + - Dephosph_AKTthr308_cplx_1175_0_ - PP2A_1154_0_ - PIP3_AKT_1246_0_ - Dephosph_AKTthr308_1174_0_ + Dephosph_AKTthr308_cplx_1148_0_ + PP2A_1127_0_ + PIP3_AKT_1219_0_ + Dephosph_AKTthr308_1147_0_ 2 470.588235294 - -462.65060241 + 462.65060241 red 46 - + - - + + - kinetics_479_0_ * k3*Dephosph_AKTthr308_cplx_1175_0_ + kinetics_451_0_ * k3*Dephosph_AKTthr308_cplx_1148_0_ - kinetics_479_0_ + kinetics_451_0_ k3 - Dephosph_AKTthr308_cplx_1175_0_ + Dephosph_AKTthr308_cplx_1148_0_ @@ -15459,49 +15906,49 @@ - + - PP2A_1154_0_ - eEFthr_56_1467_0_ - eEF2thr_56_dephospho_cplx_1178_0_ - eEF2thr_56_dephospho_1177_0_ + PP2A_1127_0_ + eEFthr_56_1440_0_ + eEF2thr_56_dephospho_cplx_1151_0_ + eEF2thr_56_dephospho_1150_0_ 1 470.588235294 - -472.289156627 + 472.289156627 red 4 - - + + - + - kinetics_479_0_ * ( k1 * PP2A_1154_0_*eEFthr_56_1467_0_ - k2 * eEF2thr_56_dephospho_cplx_1178_0_ ) + kinetics_451_0_ * ( k1 * eEFthr_56_1440_0_*PP2A_1127_0_ - k2 * eEF2thr_56_dephospho_cplx_1151_0_ ) - kinetics_479_0_ + kinetics_451_0_ k1 - PP2A_1154_0_ - eEFthr_56_1467_0_ + eEFthr_56_1440_0_ + PP2A_1127_0_ k2 - eEF2thr_56_dephospho_cplx_1178_0_ + eEF2thr_56_dephospho_cplx_1151_0_ @@ -15512,39 +15959,39 @@ - + - eEF2thr_56_dephospho_cplx_1178_0_ - PP2A_1154_0_ - eEF2_1465_0_ - eEF2thr_56_dephospho_1177_0_ + eEF2thr_56_dephospho_cplx_1151_0_ + PP2A_1127_0_ + eEF2_1438_0_ + eEF2thr_56_dephospho_1150_0_ 2 470.588235294 - -472.289156627 + 472.289156627 red 4 - + - - + + - kinetics_479_0_ * k3*eEF2thr_56_dephospho_cplx_1178_0_ + kinetics_451_0_ * k3*eEF2thr_56_dephospho_cplx_1151_0_ - kinetics_479_0_ + kinetics_451_0_ k3 - eEF2thr_56_dephospho_cplx_1178_0_ + eEF2thr_56_dephospho_cplx_1151_0_ @@ -15552,49 +15999,49 @@ - + - PP2A_1154_0_ - _4E_BP_t37_46_s65_1357_0_ - PP2A_4E_BP_p_p_cplx_1181_0_ - PP2A_4E_BP_p_p_1180_0_ + PP2A_1127_0_ + _4E_BP_t37_46_s65_1330_0_ + PP2A_4E_BP_p_p_cplx_1154_0_ + PP2A_4E_BP_p_p_1153_0_ 1 470.588235294 - -481.927710843 + 481.927710843 red 4 - - + + - + - kinetics_479_0_ * ( k1 * PP2A_1154_0_*_4E_BP_t37_46_s65_1357_0_ - k2 * PP2A_4E_BP_p_p_cplx_1181_0_ ) + kinetics_451_0_ * ( k1 * _4E_BP_t37_46_s65_1330_0_*PP2A_1127_0_ - k2 * PP2A_4E_BP_p_p_cplx_1154_0_ ) - kinetics_479_0_ + kinetics_451_0_ k1 - PP2A_1154_0_ - _4E_BP_t37_46_s65_1357_0_ + _4E_BP_t37_46_s65_1330_0_ + PP2A_1127_0_ k2 - PP2A_4E_BP_p_p_cplx_1181_0_ + PP2A_4E_BP_p_p_cplx_1154_0_ @@ -15605,39 +16052,39 @@ - + - PP2A_4E_BP_p_p_cplx_1181_0_ - PP2A_1154_0_ - _4E_BP_t37_46_1365_0_ - PP2A_4E_BP_p_p_1180_0_ + PP2A_4E_BP_p_p_cplx_1154_0_ + PP2A_1127_0_ + _4E_BP_t37_46_1338_0_ + PP2A_4E_BP_p_p_1153_0_ 2 470.588235294 - -481.927710843 + 481.927710843 red 4 - + - - + + - kinetics_479_0_ * k3*PP2A_4E_BP_p_p_cplx_1181_0_ + kinetics_451_0_ * k3*PP2A_4E_BP_p_p_cplx_1154_0_ - kinetics_479_0_ + kinetics_451_0_ k3 - PP2A_4E_BP_p_p_cplx_1181_0_ + PP2A_4E_BP_p_p_cplx_1154_0_ @@ -15645,49 +16092,49 @@ - + - PP2A_1154_0_ - _4E_BP_t37_46_1365_0_ - PP2A_4E_BP_p_cplx_1184_0_ - PP2A_4E_BP_p_1183_0_ + PP2A_1127_0_ + _4E_BP_t37_46_1338_0_ + PP2A_4E_BP_p_cplx_1157_0_ + PP2A_4E_BP_p_1156_0_ 1 470.588235294 - -491.56626506 + 491.56626506 red 4 - - + + - + - kinetics_479_0_ * ( k1 * PP2A_1154_0_*_4E_BP_t37_46_1365_0_ - k2 * PP2A_4E_BP_p_cplx_1184_0_ ) + kinetics_451_0_ * ( k1 * _4E_BP_t37_46_1338_0_*PP2A_1127_0_ - k2 * PP2A_4E_BP_p_cplx_1157_0_ ) - kinetics_479_0_ + kinetics_451_0_ k1 - PP2A_1154_0_ - _4E_BP_t37_46_1365_0_ + _4E_BP_t37_46_1338_0_ + PP2A_1127_0_ k2 - PP2A_4E_BP_p_cplx_1184_0_ + PP2A_4E_BP_p_cplx_1157_0_ @@ -15698,39 +16145,39 @@ - + - PP2A_4E_BP_p_cplx_1184_0_ - PP2A_1154_0_ - _4E_BP_1355_0_ - PP2A_4E_BP_p_1183_0_ + PP2A_4E_BP_p_cplx_1157_0_ + PP2A_1127_0_ + _4E_BP_1328_0_ + PP2A_4E_BP_p_1156_0_ 2 470.588235294 - -491.56626506 + 491.56626506 red 4 - + - - + + - kinetics_479_0_ * k3*PP2A_4E_BP_p_cplx_1184_0_ + kinetics_451_0_ * k3*PP2A_4E_BP_p_cplx_1157_0_ - kinetics_479_0_ + kinetics_451_0_ k3 - PP2A_4E_BP_p_cplx_1184_0_ + PP2A_4E_BP_p_cplx_1157_0_ @@ -15738,49 +16185,49 @@ - + - PP2A_1154_0_ - eIF4E_BP_t37_46_s65_1363_0_ - PP2A_4E_BP_cplx_1187_0_ - PP2A_4E_BP_1186_0_ + PP2A_1127_0_ + eIF4E_BP_t37_46_s65_1336_0_ + PP2A_4E_BP_cplx_1160_0_ + PP2A_4E_BP_1159_0_ 1 470.588235294 - -501.204819277 + 501.204819277 red 62 - - + + - + - kinetics_479_0_ * ( k1 * PP2A_1154_0_*eIF4E_BP_t37_46_s65_1363_0_ - k2 * PP2A_4E_BP_cplx_1187_0_ ) + kinetics_451_0_ * ( k1 * eIF4E_BP_t37_46_s65_1336_0_*PP2A_1127_0_ - k2 * PP2A_4E_BP_cplx_1160_0_ ) - kinetics_479_0_ + kinetics_451_0_ k1 - PP2A_1154_0_ - eIF4E_BP_t37_46_s65_1363_0_ + eIF4E_BP_t37_46_s65_1336_0_ + PP2A_1127_0_ k2 - PP2A_4E_BP_cplx_1187_0_ + PP2A_4E_BP_cplx_1160_0_ @@ -15791,39 +16238,39 @@ - + - PP2A_4E_BP_cplx_1187_0_ - PP2A_1154_0_ - eIF4E_BP_thr37_46_1361_0_ - PP2A_4E_BP_1186_0_ + PP2A_4E_BP_cplx_1160_0_ + PP2A_1127_0_ + eIF4E_BP_thr37_46_1334_0_ + PP2A_4E_BP_1159_0_ 2 470.588235294 - -501.204819277 + 501.204819277 red 62 - + - - + + - kinetics_479_0_ * k3*PP2A_4E_BP_cplx_1187_0_ + kinetics_451_0_ * k3*PP2A_4E_BP_cplx_1160_0_ - kinetics_479_0_ + kinetics_451_0_ k3 - PP2A_4E_BP_cplx_1187_0_ + PP2A_4E_BP_cplx_1160_0_ @@ -15831,49 +16278,49 @@ - + - PP2A_1154_0_ - eIF4E_BP_thr37_46_1361_0_ - PP2A_4EBP_cplx_1190_0_ - PP2A_4EBP_1189_0_ + PP2A_1127_0_ + eIF4E_BP_thr37_46_1334_0_ + PP2A_4EBP_cplx_1163_0_ + PP2A_4EBP_1162_0_ 1 470.588235294 - -510.843373494 + 510.843373494 red 62 - - + + - + - kinetics_479_0_ * ( k1 * eIF4E_BP_thr37_46_1361_0_*PP2A_1154_0_ - k2 * PP2A_4EBP_cplx_1190_0_ ) + kinetics_451_0_ * ( k1 * eIF4E_BP_thr37_46_1334_0_*PP2A_1127_0_ - k2 * PP2A_4EBP_cplx_1163_0_ ) - kinetics_479_0_ + kinetics_451_0_ k1 - eIF4E_BP_thr37_46_1361_0_ - PP2A_1154_0_ + eIF4E_BP_thr37_46_1334_0_ + PP2A_1127_0_ k2 - PP2A_4EBP_cplx_1190_0_ + PP2A_4EBP_cplx_1163_0_ @@ -15884,39 +16331,39 @@ - + - PP2A_4EBP_cplx_1190_0_ - PP2A_1154_0_ - eIF4E_BP_1359_0_ - PP2A_4EBP_1189_0_ + PP2A_4EBP_cplx_1163_0_ + PP2A_1127_0_ + eIF4E_BP_1332_0_ + PP2A_4EBP_1162_0_ 2 470.588235294 - -510.843373494 + 510.843373494 red 62 - + - - + + - kinetics_479_0_ * k3*PP2A_4EBP_cplx_1190_0_ + kinetics_451_0_ * k3*PP2A_4EBP_cplx_1163_0_ - kinetics_479_0_ + kinetics_451_0_ k3 - PP2A_4EBP_cplx_1190_0_ + PP2A_4EBP_cplx_1163_0_ @@ -15924,49 +16371,49 @@ - + - PP2A_1154_0_ - Internal_mGluR_p_1553_0_ - mGluR_dephosph_cplx_1193_0_ - mGluR_dephosph_1192_0_ + PP2A_1127_0_ + Internal_mGluR_p_1526_0_ + mGluR_dephosph_cplx_1166_0_ + mGluR_dephosph_1165_0_ 1 470.588235294 - -520.481927711 + 520.481927711 23 black - - + + - + - kinetics_479_0_ * ( k1 * Internal_mGluR_p_1553_0_*PP2A_1154_0_ - k2 * mGluR_dephosph_cplx_1193_0_ ) + kinetics_451_0_ * ( k1 * Internal_mGluR_p_1526_0_*PP2A_1127_0_ - k2 * mGluR_dephosph_cplx_1166_0_ ) - kinetics_479_0_ + kinetics_451_0_ k1 - Internal_mGluR_p_1553_0_ - PP2A_1154_0_ + Internal_mGluR_p_1526_0_ + PP2A_1127_0_ k2 - mGluR_dephosph_cplx_1193_0_ + mGluR_dephosph_cplx_1166_0_ @@ -15977,39 +16424,39 @@ - + - mGluR_dephosph_cplx_1193_0_ - PP2A_1154_0_ - Internal_mGluR_1551_0_ - mGluR_dephosph_1192_0_ + mGluR_dephosph_cplx_1166_0_ + PP2A_1127_0_ + Internal_mGluR_1524_0_ + mGluR_dephosph_1165_0_ 2 470.588235294 - -520.481927711 + 520.481927711 23 black - + - - + + - kinetics_479_0_ * k3*mGluR_dephosph_cplx_1193_0_ + kinetics_451_0_ * k3*mGluR_dephosph_cplx_1166_0_ - kinetics_479_0_ + kinetics_451_0_ k3 - mGluR_dephosph_cplx_1193_0_ + mGluR_dephosph_cplx_1166_0_ @@ -16017,49 +16464,49 @@ - + - PDK1_1205_0_ - S6K_thr_412_1331_0_ - S6K_phospho_cplx_1208_0_ - S6K_phospho_1207_0_ + PDK1_1178_0_ + S6K_thr_412_1304_0_ + S6K_phospho_cplx_1181_0_ + S6K_phospho_1180_0_ 1 794.117647059 - -404.819277108 + 404.819277108 red 37 - - + + - + - kinetics_479_0_ * ( k1 * S6K_thr_412_1331_0_*PDK1_1205_0_ - k2 * S6K_phospho_cplx_1208_0_ ) + kinetics_451_0_ * ( k1 * S6K_thr_412_1304_0_*PDK1_1178_0_ - k2 * S6K_phospho_cplx_1181_0_ ) - kinetics_479_0_ + kinetics_451_0_ k1 - S6K_thr_412_1331_0_ - PDK1_1205_0_ + S6K_thr_412_1304_0_ + PDK1_1178_0_ k2 - S6K_phospho_cplx_1208_0_ + S6K_phospho_cplx_1181_0_ @@ -16070,39 +16517,39 @@ - + - S6K_phospho_cplx_1208_0_ - PDK1_1205_0_ - S6K_thr_252_1336_0_ - S6K_phospho_1207_0_ + S6K_phospho_cplx_1181_0_ + PDK1_1178_0_ + S6K_thr_252_1309_0_ + S6K_phospho_1180_0_ 2 794.117647059 - -404.819277108 + 404.819277108 red 37 - + - - + + - kinetics_479_0_ * k3*S6K_phospho_cplx_1208_0_ + kinetics_451_0_ * k3*S6K_phospho_cplx_1181_0_ - kinetics_479_0_ + kinetics_451_0_ k3 - S6K_phospho_cplx_1208_0_ + S6K_phospho_cplx_1181_0_ @@ -16110,49 +16557,49 @@ - + - SHC_p_Grb2_Gab1_PI3K_clx_1210_0_ - PIP2_636_0_ - Phospho_cplx_1213_0_ - Phospho_1212_0_ + SHC_p_Grb2_Gab1_PI3K_clx_1183_0_ + PIP2_609_0_ + Phospho_cplx_1186_0_ + Phospho_1185_0_ 1 808.823529412 - -404.819277108 + 404.819277108 red brown - - + + - + - kinetics_479_0_ * ( k1 * SHC_p_Grb2_Gab1_PI3K_clx_1210_0_*PIP2_636_0_ - k2 * Phospho_cplx_1213_0_ ) + kinetics_451_0_ * ( k1 * PIP2_609_0_*SHC_p_Grb2_Gab1_PI3K_clx_1183_0_ - k2 * Phospho_cplx_1186_0_ ) - kinetics_479_0_ + kinetics_451_0_ k1 - SHC_p_Grb2_Gab1_PI3K_clx_1210_0_ - PIP2_636_0_ + PIP2_609_0_ + SHC_p_Grb2_Gab1_PI3K_clx_1183_0_ k2 - Phospho_cplx_1213_0_ + Phospho_cplx_1186_0_ @@ -16163,39 +16610,39 @@ - + - Phospho_cplx_1213_0_ - SHC_p_Grb2_Gab1_PI3K_clx_1210_0_ - PIP3_1203_0_ - Phospho_1212_0_ + Phospho_cplx_1186_0_ + SHC_p_Grb2_Gab1_PI3K_clx_1183_0_ + PIP3_1176_0_ + Phospho_1185_0_ 2 808.823529412 - -404.819277108 + 404.819277108 red brown - + - - + + - kinetics_479_0_ * k3*Phospho_cplx_1213_0_ + kinetics_451_0_ * k3*Phospho_cplx_1186_0_ - kinetics_479_0_ + kinetics_451_0_ k3 - Phospho_cplx_1213_0_ + Phospho_cplx_1186_0_ @@ -16203,49 +16650,49 @@ - + - PI3K_basal_1217_0_ - PIP2_636_0_ - basal_phosp_cplx_1220_0_ - basal_phosp_1219_0_ + PI3K_basal_1190_0_ + PIP2_609_0_ + basal_phosp_cplx_1193_0_ + basal_phosp_1192_0_ 1 838.235294118 - -404.819277108 + 404.819277108 red 10 - - + + - + - kinetics_479_0_ * ( k1 * PI3K_basal_1217_0_*PIP2_636_0_ - k2 * basal_phosp_cplx_1220_0_ ) + kinetics_451_0_ * ( k1 * PIP2_609_0_*PI3K_basal_1190_0_ - k2 * basal_phosp_cplx_1193_0_ ) - kinetics_479_0_ + kinetics_451_0_ k1 - PI3K_basal_1217_0_ - PIP2_636_0_ + PIP2_609_0_ + PI3K_basal_1190_0_ k2 - basal_phosp_cplx_1220_0_ + basal_phosp_cplx_1193_0_ @@ -16256,39 +16703,39 @@ - + - basal_phosp_cplx_1220_0_ - PI3K_basal_1217_0_ - PIP3_1203_0_ - basal_phosp_1219_0_ + basal_phosp_cplx_1193_0_ + PI3K_basal_1190_0_ + PIP3_1176_0_ + basal_phosp_1192_0_ 2 838.235294118 - -404.819277108 + 404.819277108 red 10 - + - - + + - kinetics_479_0_ * k3*basal_phosp_cplx_1220_0_ + kinetics_451_0_ * k3*basal_phosp_cplx_1193_0_ - kinetics_479_0_ + kinetics_451_0_ k3 - basal_phosp_cplx_1220_0_ + basal_phosp_cplx_1193_0_ @@ -16296,49 +16743,49 @@ - + - PTEN_1226_0_ - PIP3_1203_0_ - PIP3_dephosp_cplx_1229_0_ - PIP3_dephosp_1228_0_ + PTEN_1199_0_ + PIP3_1176_0_ + PIP3_dephosp_cplx_1202_0_ + PIP3_dephosp_1201_0_ 1 757.352941176 - -510.843373494 + 510.843373494 red 37 - - + + - + - kinetics_479_0_ * ( k1 * PTEN_1226_0_*PIP3_1203_0_ - k2 * PIP3_dephosp_cplx_1229_0_ ) + kinetics_451_0_ * ( k1 * PIP3_1176_0_*PTEN_1199_0_ - k2 * PIP3_dephosp_cplx_1202_0_ ) - kinetics_479_0_ + kinetics_451_0_ k1 - PTEN_1226_0_ - PIP3_1203_0_ + PIP3_1176_0_ + PTEN_1199_0_ k2 - PIP3_dephosp_cplx_1229_0_ + PIP3_dephosp_cplx_1202_0_ @@ -16349,39 +16796,39 @@ - + - PIP3_dephosp_cplx_1229_0_ - PTEN_1226_0_ - PIP2_636_0_ - PIP3_dephosp_1228_0_ + PIP3_dephosp_cplx_1202_0_ + PTEN_1199_0_ + PIP2_609_0_ + PIP3_dephosp_1201_0_ 2 757.352941176 - -510.843373494 + 510.843373494 red 37 - + - - + + - kinetics_479_0_ * k3*PIP3_dephosp_cplx_1229_0_ + kinetics_451_0_ * k3*PIP3_dephosp_cplx_1202_0_ - kinetics_479_0_ + kinetics_451_0_ k3 - PIP3_dephosp_cplx_1229_0_ + PIP3_dephosp_cplx_1202_0_ @@ -16389,49 +16836,49 @@ - + - Ras_GTP_PI3K_1237_0_ - PIP2_636_0_ - PIP2_phospho_Ras_GTP_cplx_1240_0_ - PIP2_phospho_Ras_GTP_1239_0_ + Ras_GTP_PI3K_1210_0_ + PIP2_609_0_ + PIP2_phospho_Ras_GTP_cplx_1213_0_ + PIP2_phospho_Ras_GTP_1212_0_ 1 794.117647059 - -510.843373494 + 510.843373494 red 31 - - + + - + - kinetics_479_0_ * ( k1 * PIP2_636_0_*Ras_GTP_PI3K_1237_0_ - k2 * PIP2_phospho_Ras_GTP_cplx_1240_0_ ) + kinetics_451_0_ * ( k1 * PIP2_609_0_*Ras_GTP_PI3K_1210_0_ - k2 * PIP2_phospho_Ras_GTP_cplx_1213_0_ ) - kinetics_479_0_ + kinetics_451_0_ k1 - PIP2_636_0_ - Ras_GTP_PI3K_1237_0_ + PIP2_609_0_ + Ras_GTP_PI3K_1210_0_ k2 - PIP2_phospho_Ras_GTP_cplx_1240_0_ + PIP2_phospho_Ras_GTP_cplx_1213_0_ @@ -16442,39 +16889,39 @@ - + - PIP2_phospho_Ras_GTP_cplx_1240_0_ - Ras_GTP_PI3K_1237_0_ - PIP3_1203_0_ - PIP2_phospho_Ras_GTP_1239_0_ + PIP2_phospho_Ras_GTP_cplx_1213_0_ + Ras_GTP_PI3K_1210_0_ + PIP3_1176_0_ + PIP2_phospho_Ras_GTP_1212_0_ 2 794.117647059 - -510.843373494 + 510.843373494 red 31 - + - - + + - kinetics_479_0_ * k3*PIP2_phospho_Ras_GTP_cplx_1240_0_ + kinetics_451_0_ * k3*PIP2_phospho_Ras_GTP_cplx_1213_0_ - kinetics_479_0_ + kinetics_451_0_ k3 - PIP2_phospho_Ras_GTP_cplx_1240_0_ + PIP2_phospho_Ras_GTP_cplx_1213_0_ @@ -16482,49 +16929,49 @@ - + - PIP3_PDK1_1248_0_ - PIP3_AKT_1246_0_ - phospho_thr308_cplx_1251_0_ - phospho_thr308_1250_0_ + PIP3_PDK1_1221_0_ + PIP3_AKT_1219_0_ + phospho_thr308_cplx_1224_0_ + phospho_thr308_1223_0_ 1 897.058823529 - -404.819277108 + 404.819277108 red 9 - - + + - + - kinetics_479_0_ * ( k1 * PIP3_PDK1_1248_0_*PIP3_AKT_1246_0_ - k2 * phospho_thr308_cplx_1251_0_ ) + kinetics_451_0_ * ( k1 * PIP3_AKT_1219_0_*PIP3_PDK1_1221_0_ - k2 * phospho_thr308_cplx_1224_0_ ) - kinetics_479_0_ + kinetics_451_0_ k1 - PIP3_PDK1_1248_0_ - PIP3_AKT_1246_0_ + PIP3_AKT_1219_0_ + PIP3_PDK1_1221_0_ k2 - phospho_thr308_cplx_1251_0_ + phospho_thr308_cplx_1224_0_ @@ -16535,39 +16982,39 @@ - + - phospho_thr308_cplx_1251_0_ - PIP3_PDK1_1248_0_ - PIP3_AKT_thr308_1258_0_ - phospho_thr308_1250_0_ + phospho_thr308_cplx_1224_0_ + PIP3_PDK1_1221_0_ + PIP3_AKT_thr308_1231_0_ + phospho_thr308_1223_0_ 2 897.058823529 - -404.819277108 + 404.819277108 red 9 - + - - + + - kinetics_479_0_ * k3*phospho_thr308_cplx_1251_0_ + kinetics_451_0_ * k3*phospho_thr308_cplx_1224_0_ - kinetics_479_0_ + kinetics_451_0_ k3 - phospho_thr308_cplx_1251_0_ + phospho_thr308_cplx_1224_0_ @@ -16575,49 +17022,49 @@ - + - PIP3_PDK2_1253_0_ - PIP3_AKT_thr308_1258_0_ - phosp_AKTser473_cplx_1256_0_ - phosp_AKTser473_1255_0_ + PIP3_PDK2_1226_0_ + PIP3_AKT_thr308_1231_0_ + phosp_AKTser473_cplx_1229_0_ + phosp_AKTser473_1228_0_ 1 911.764705882 - -404.819277108 + 404.819277108 red 39 - - + + - + - kinetics_479_0_ * ( k1 * PIP3_AKT_thr308_1258_0_*PIP3_PDK2_1253_0_ - k2 * phosp_AKTser473_cplx_1256_0_ ) + kinetics_451_0_ * ( k1 * PIP3_PDK2_1226_0_*PIP3_AKT_thr308_1231_0_ - k2 * phosp_AKTser473_cplx_1229_0_ ) - kinetics_479_0_ + kinetics_451_0_ k1 - PIP3_AKT_thr308_1258_0_ - PIP3_PDK2_1253_0_ + PIP3_PDK2_1226_0_ + PIP3_AKT_thr308_1231_0_ k2 - phosp_AKTser473_cplx_1256_0_ + phosp_AKTser473_cplx_1229_0_ @@ -16628,39 +17075,39 @@ - + - phosp_AKTser473_cplx_1256_0_ - PIP3_PDK2_1253_0_ - PIP3_AKT_t308_s473_1260_0_ - phosp_AKTser473_1255_0_ + phosp_AKTser473_cplx_1229_0_ + PIP3_PDK2_1226_0_ + PIP3_AKT_t308_s473_1233_0_ + phosp_AKTser473_1228_0_ 2 911.764705882 - -404.819277108 + 404.819277108 red 39 - + - - + + - kinetics_479_0_ * k3*phosp_AKTser473_cplx_1256_0_ + kinetics_451_0_ * k3*phosp_AKTser473_cplx_1229_0_ - kinetics_479_0_ + kinetics_451_0_ k3 - phosp_AKTser473_cplx_1256_0_ + phosp_AKTser473_cplx_1229_0_ @@ -16668,49 +17115,49 @@ - + - PIP3_AKT_t308_s473_1260_0_ - TSC1_TSC2_1508_0_ - TSC2_phospho_cplx_1263_0_ - TSC2_phospho_1262_0_ + PIP3_AKT_t308_s473_1233_0_ + TSC1_TSC2_1481_0_ + TSC2_phospho_cplx_1236_0_ + TSC2_phospho_1235_0_ 1 941.176470588 - -404.819277108 + 404.819277108 red 25 - - + + - + - kinetics_479_0_ * ( k1 * TSC1_TSC2_1508_0_*PIP3_AKT_t308_s473_1260_0_ - k2 * TSC2_phospho_cplx_1263_0_ ) + kinetics_451_0_ * ( k1 * PIP3_AKT_t308_s473_1233_0_*TSC1_TSC2_1481_0_ - k2 * TSC2_phospho_cplx_1236_0_ ) - kinetics_479_0_ + kinetics_451_0_ k1 - TSC1_TSC2_1508_0_ - PIP3_AKT_t308_s473_1260_0_ + PIP3_AKT_t308_s473_1233_0_ + TSC1_TSC2_1481_0_ k2 - TSC2_phospho_cplx_1263_0_ + TSC2_phospho_cplx_1236_0_ @@ -16721,39 +17168,39 @@ - + - TSC2_phospho_cplx_1263_0_ - PIP3_AKT_t308_s473_1260_0_ - TSC1_TSC2_p_1506_0_ - TSC2_phospho_1262_0_ + TSC2_phospho_cplx_1236_0_ + PIP3_AKT_t308_s473_1233_0_ + TSC1_TSC2_p_1479_0_ + TSC2_phospho_1235_0_ 2 941.176470588 - -404.819277108 + 404.819277108 red 25 - + - - + + - kinetics_479_0_ * k3*TSC2_phospho_cplx_1263_0_ + kinetics_451_0_ * k3*TSC2_phospho_cplx_1236_0_ - kinetics_479_0_ + kinetics_451_0_ k3 - TSC2_phospho_cplx_1263_0_ + TSC2_phospho_cplx_1236_0_ @@ -16761,49 +17208,49 @@ - + - PIP3_AKT_t308_s473_1260_0_ - craf_1_668_0_ - Enz_cplx_1266_0_ - Enz_1265_0_ + PIP3_AKT_t308_s473_1233_0_ + craf_1_641_0_ + Enz_cplx_1239_0_ + Enz_1238_0_ 1 941.176470588 - -414.457831325 + 414.457831325 black 19 - - + + - + - kinetics_479_0_ * ( k1 * craf_1_668_0_*PIP3_AKT_t308_s473_1260_0_ - k2 * Enz_cplx_1266_0_ ) + kinetics_451_0_ * ( k1 * PIP3_AKT_t308_s473_1233_0_*craf_1_641_0_ - k2 * Enz_cplx_1239_0_ ) - kinetics_479_0_ + kinetics_451_0_ k1 - craf_1_668_0_ - PIP3_AKT_t308_s473_1260_0_ + PIP3_AKT_t308_s473_1233_0_ + craf_1_641_0_ k2 - Enz_cplx_1266_0_ + Enz_cplx_1239_0_ @@ -16814,39 +17261,39 @@ - + - Enz_cplx_1266_0_ - PIP3_AKT_t308_s473_1260_0_ - craf_1_p_ser259_704_0_ - Enz_1265_0_ + Enz_cplx_1239_0_ + PIP3_AKT_t308_s473_1233_0_ + craf_1_p_ser259_677_0_ + Enz_1238_0_ 2 941.176470588 - -414.457831325 + 414.457831325 black 19 - + - - + + - kinetics_479_0_ * k3*Enz_cplx_1266_0_ + kinetics_451_0_ * k3*Enz_cplx_1239_0_ - kinetics_479_0_ + kinetics_451_0_ k3 - Enz_cplx_1266_0_ + Enz_cplx_1239_0_ @@ -16854,49 +17301,49 @@ - + - BDNF_TrKB2_p_clx_1284_0_ - PLC_g_814_0_ - PLC_g_phospho_cplx_1287_0_ - PLC_g_phospho_1286_0_ + BDNF_TrKB2_p_clx_1257_0_ + PLC_g_787_0_ + PLC_g_phospho_cplx_1260_0_ + PLC_g_phospho_1259_0_ 1 58.8235294118 - -597.590361446 + 597.590361446 red red - - + + - + - kinetics_479_0_ * ( k1 * BDNF_TrKB2_p_clx_1284_0_*PLC_g_814_0_ - k2 * PLC_g_phospho_cplx_1287_0_ ) + kinetics_451_0_ * ( k1 * BDNF_TrKB2_p_clx_1257_0_*PLC_g_787_0_ - k2 * PLC_g_phospho_cplx_1260_0_ ) - kinetics_479_0_ + kinetics_451_0_ k1 - BDNF_TrKB2_p_clx_1284_0_ - PLC_g_814_0_ + BDNF_TrKB2_p_clx_1257_0_ + PLC_g_787_0_ k2 - PLC_g_phospho_cplx_1287_0_ + PLC_g_phospho_cplx_1260_0_ @@ -16907,39 +17354,39 @@ - + - PLC_g_phospho_cplx_1287_0_ - BDNF_TrKB2_p_clx_1284_0_ - PLC_g_p_816_0_ - PLC_g_phospho_1286_0_ + PLC_g_phospho_cplx_1260_0_ + BDNF_TrKB2_p_clx_1257_0_ + PLC_g_p_789_0_ + PLC_g_phospho_1259_0_ 2 58.8235294118 - -597.590361446 + 597.590361446 red red - + - - + + - kinetics_479_0_ * k3*PLC_g_phospho_cplx_1287_0_ + kinetics_451_0_ * k3*PLC_g_phospho_cplx_1260_0_ - kinetics_479_0_ + kinetics_451_0_ k3 - PLC_g_phospho_cplx_1287_0_ + PLC_g_phospho_cplx_1260_0_ @@ -16947,49 +17394,49 @@ - + - BDNF_TrKB2_p_clx_1284_0_ - SHC_784_0_ - SHC_phospho_cplx_1290_0_ - SHC_phospho_1289_0_ + BDNF_TrKB2_p_clx_1257_0_ + SHC_757_0_ + SHC_phospho_cplx_1263_0_ + SHC_phospho_1262_0_ 1 58.8235294118 - -607.228915663 + 607.228915663 red red - - + + - + - kinetics_479_0_ * ( k1 * SHC_784_0_*BDNF_TrKB2_p_clx_1284_0_ - k2 * SHC_phospho_cplx_1290_0_ ) + kinetics_451_0_ * ( k1 * BDNF_TrKB2_p_clx_1257_0_*SHC_757_0_ - k2 * SHC_phospho_cplx_1263_0_ ) - kinetics_479_0_ + kinetics_451_0_ k1 - SHC_784_0_ - BDNF_TrKB2_p_clx_1284_0_ + BDNF_TrKB2_p_clx_1257_0_ + SHC_757_0_ k2 - SHC_phospho_cplx_1290_0_ + SHC_phospho_cplx_1263_0_ @@ -17000,39 +17447,39 @@ - + - SHC_phospho_cplx_1290_0_ - BDNF_TrKB2_p_clx_1284_0_ - SHC_p_786_0_ - SHC_phospho_1289_0_ + SHC_phospho_cplx_1263_0_ + BDNF_TrKB2_p_clx_1257_0_ + SHC_p_759_0_ + SHC_phospho_1262_0_ 2 58.8235294118 - -607.228915663 + 607.228915663 red red - + - - + + - kinetics_479_0_ * k3*SHC_phospho_cplx_1290_0_ + kinetics_451_0_ * k3*SHC_phospho_cplx_1263_0_ - kinetics_479_0_ + kinetics_451_0_ k3 - SHC_phospho_cplx_1290_0_ + SHC_phospho_cplx_1263_0_ @@ -17040,49 +17487,49 @@ - + - TOR_Rheb_GTP_clx_1310_0_ - S6K_p_1327_0_ - S6K_phospho_cplx_1313_0_ - S6K_phospho_1312_0_ + TOR_Rheb_GTP_clx_1283_0_ + S6K_p_1300_0_ + S6K_phospho_cplx_1286_0_ + S6K_phospho_1285_0_ 1 191.176470588 - -597.590361446 + 597.590361446 red 42 - - + + - + - kinetics_479_0_ * ( k1 * TOR_Rheb_GTP_clx_1310_0_*S6K_p_1327_0_ - k2 * S6K_phospho_cplx_1313_0_ ) + kinetics_451_0_ * ( k1 * TOR_Rheb_GTP_clx_1283_0_*S6K_p_1300_0_ - k2 * S6K_phospho_cplx_1286_0_ ) - kinetics_479_0_ + kinetics_451_0_ k1 - TOR_Rheb_GTP_clx_1310_0_ - S6K_p_1327_0_ + TOR_Rheb_GTP_clx_1283_0_ + S6K_p_1300_0_ k2 - S6K_phospho_cplx_1313_0_ + S6K_phospho_cplx_1286_0_ @@ -17093,39 +17540,39 @@ - + - S6K_phospho_cplx_1313_0_ - TOR_Rheb_GTP_clx_1310_0_ - S6K_thr_412_1331_0_ - S6K_phospho_1312_0_ + S6K_phospho_cplx_1286_0_ + TOR_Rheb_GTP_clx_1283_0_ + S6K_thr_412_1304_0_ + S6K_phospho_1285_0_ 2 191.176470588 - -597.590361446 + 597.590361446 red 42 - + - - + + - kinetics_479_0_ * k3*S6K_phospho_cplx_1313_0_ + kinetics_451_0_ * k3*S6K_phospho_cplx_1286_0_ - kinetics_479_0_ + kinetics_451_0_ k3 - S6K_phospho_cplx_1313_0_ + S6K_phospho_cplx_1286_0_ @@ -17133,49 +17580,49 @@ - + - TOR_Rheb_GTP_clx_1310_0_ - eIF4E_BP_1359_0_ - TOR_4E_BP_phospho_cplx_1316_0_ - TOR_4E_BP_phospho_1315_0_ + TOR_Rheb_GTP_clx_1283_0_ + eIF4E_BP_1332_0_ + TOR_4E_BP_phospho_cplx_1289_0_ + TOR_4E_BP_phospho_1288_0_ 1 191.176470588 - -607.228915663 + 607.228915663 red 44 - - + + - + - kinetics_479_0_ * ( k1 * TOR_Rheb_GTP_clx_1310_0_*eIF4E_BP_1359_0_ - k2 * TOR_4E_BP_phospho_cplx_1316_0_ ) + kinetics_451_0_ * ( k1 * TOR_Rheb_GTP_clx_1283_0_*eIF4E_BP_1332_0_ - k2 * TOR_4E_BP_phospho_cplx_1289_0_ ) - kinetics_479_0_ + kinetics_451_0_ k1 - TOR_Rheb_GTP_clx_1310_0_ - eIF4E_BP_1359_0_ + TOR_Rheb_GTP_clx_1283_0_ + eIF4E_BP_1332_0_ k2 - TOR_4E_BP_phospho_cplx_1316_0_ + TOR_4E_BP_phospho_cplx_1289_0_ @@ -17186,39 +17633,39 @@ - + - TOR_4E_BP_phospho_cplx_1316_0_ - TOR_Rheb_GTP_clx_1310_0_ - eIF4E_BP_thr37_46_1361_0_ - TOR_4E_BP_phospho_1315_0_ + TOR_4E_BP_phospho_cplx_1289_0_ + TOR_Rheb_GTP_clx_1283_0_ + eIF4E_BP_thr37_46_1334_0_ + TOR_4E_BP_phospho_1288_0_ 2 191.176470588 - -607.228915663 + 607.228915663 red 44 - + - - + + - kinetics_479_0_ * k3*TOR_4E_BP_phospho_cplx_1316_0_ + kinetics_451_0_ * k3*TOR_4E_BP_phospho_cplx_1289_0_ - kinetics_479_0_ + kinetics_451_0_ k3 - TOR_4E_BP_phospho_cplx_1316_0_ + TOR_4E_BP_phospho_cplx_1289_0_ @@ -17226,49 +17673,49 @@ - + - TOR_Rheb_GTP_clx_1310_0_ - _4E_BP_1355_0_ - TOR_4E_BP_p_cplx_1319_0_ - TOR_4E_BP_p_1318_0_ + TOR_Rheb_GTP_clx_1283_0_ + _4E_BP_1328_0_ + TOR_4E_BP_p_cplx_1292_0_ + TOR_4E_BP_p_1291_0_ 1 191.176470588 - -616.86746988 + 616.86746988 red 44 - - + + - + - kinetics_479_0_ * ( k1 * _4E_BP_1355_0_*TOR_Rheb_GTP_clx_1310_0_ - k2 * TOR_4E_BP_p_cplx_1319_0_ ) + kinetics_451_0_ * ( k1 * _4E_BP_1328_0_*TOR_Rheb_GTP_clx_1283_0_ - k2 * TOR_4E_BP_p_cplx_1292_0_ ) - kinetics_479_0_ + kinetics_451_0_ k1 - _4E_BP_1355_0_ - TOR_Rheb_GTP_clx_1310_0_ + _4E_BP_1328_0_ + TOR_Rheb_GTP_clx_1283_0_ k2 - TOR_4E_BP_p_cplx_1319_0_ + TOR_4E_BP_p_cplx_1292_0_ @@ -17279,39 +17726,39 @@ - + - TOR_4E_BP_p_cplx_1319_0_ - TOR_Rheb_GTP_clx_1310_0_ - _4E_BP_t37_46_1365_0_ - TOR_4E_BP_p_1318_0_ + TOR_4E_BP_p_cplx_1292_0_ + TOR_Rheb_GTP_clx_1283_0_ + _4E_BP_t37_46_1338_0_ + TOR_4E_BP_p_1291_0_ 2 191.176470588 - -616.86746988 + 616.86746988 red 44 - + - - + + - kinetics_479_0_ * k3*TOR_4E_BP_p_cplx_1319_0_ + kinetics_451_0_ * k3*TOR_4E_BP_p_cplx_1292_0_ - kinetics_479_0_ + kinetics_451_0_ k3 - TOR_4E_BP_p_cplx_1319_0_ + TOR_4E_BP_p_cplx_1292_0_ @@ -17319,49 +17766,49 @@ - + - S6K_thr_412_1331_0_ - _40S_inact_1495_0_ - S6_phos_cplx_1334_0_ - S6_phos_1333_0_ + S6K_thr_412_1304_0_ + _40S_inact_1468_0_ + S6_phos_cplx_1307_0_ + S6_phos_1306_0_ 1 323.529411765 - -597.590361446 + 597.590361446 red 48 - - + + - + - kinetics_479_0_ * ( k1 * S6K_thr_412_1331_0_*_40S_inact_1495_0_ - k2 * S6_phos_cplx_1334_0_ ) + kinetics_451_0_ * ( k1 * S6K_thr_412_1304_0_*_40S_inact_1468_0_ - k2 * S6_phos_cplx_1307_0_ ) - kinetics_479_0_ + kinetics_451_0_ k1 - S6K_thr_412_1331_0_ - _40S_inact_1495_0_ + S6K_thr_412_1304_0_ + _40S_inact_1468_0_ k2 - S6_phos_cplx_1334_0_ + S6_phos_cplx_1307_0_ @@ -17372,39 +17819,39 @@ - + - S6_phos_cplx_1334_0_ - S6K_thr_412_1331_0_ - _40S_1497_0_ - S6_phos_1333_0_ + S6_phos_cplx_1307_0_ + S6K_thr_412_1304_0_ + _40S_1470_0_ + S6_phos_1306_0_ 2 323.529411765 - -597.590361446 + 597.590361446 red 48 - + - - + + - kinetics_479_0_ * k3*S6_phos_cplx_1334_0_ + kinetics_451_0_ * k3*S6_phos_cplx_1307_0_ - kinetics_479_0_ + kinetics_451_0_ k3 - S6_phos_cplx_1334_0_ + S6_phos_cplx_1307_0_ @@ -17412,49 +17859,49 @@ - + - S6K_thr_252_1336_0_ - CaMKIII_1425_0_ - CaMKIII_phospho_cplx_1339_0_ - CaMKIII_phospho_1338_0_ + S6K_thr_252_1309_0_ + CaMKIII_1398_0_ + CaMKIII_phospho_cplx_1312_0_ + CaMKIII_phospho_1311_0_ 1 338.235294118 - -597.590361446 + 597.590361446 red 6 - - + + - + - kinetics_479_0_ * ( k1 * S6K_thr_252_1336_0_*CaMKIII_1425_0_ - k2 * CaMKIII_phospho_cplx_1339_0_ ) + kinetics_451_0_ * ( k1 * S6K_thr_252_1309_0_*CaMKIII_1398_0_ - k2 * CaMKIII_phospho_cplx_1312_0_ ) - kinetics_479_0_ + kinetics_451_0_ k1 - S6K_thr_252_1336_0_ - CaMKIII_1425_0_ + S6K_thr_252_1309_0_ + CaMKIII_1398_0_ k2 - CaMKIII_phospho_cplx_1339_0_ + CaMKIII_phospho_cplx_1312_0_ @@ -17465,39 +17912,39 @@ - + - CaMKIII_phospho_cplx_1339_0_ - S6K_thr_252_1336_0_ - CaMKIII_p_1437_0_ - CaMKIII_phospho_1338_0_ + CaMKIII_phospho_cplx_1312_0_ + S6K_thr_252_1309_0_ + CaMKIII_p_1410_0_ + CaMKIII_phospho_1311_0_ 2 338.235294118 - -597.590361446 + 597.590361446 red 6 - + - - + + - kinetics_479_0_ * k3*CaMKIII_phospho_cplx_1339_0_ + kinetics_451_0_ * k3*CaMKIII_phospho_cplx_1312_0_ - kinetics_479_0_ + kinetics_451_0_ k3 - CaMKIII_phospho_cplx_1339_0_ + CaMKIII_phospho_cplx_1312_0_ @@ -17505,49 +17952,49 @@ - + - S6K_thr_252_1336_0_ - _40S_inact_1495_0_ - S6_phospho_cplx_1342_0_ - S6_phospho_1341_0_ + S6K_thr_252_1309_0_ + _40S_inact_1468_0_ + S6_phospho_cplx_1315_0_ + S6_phospho_1314_0_ 1 338.235294118 - -607.228915663 + 607.228915663 red 4 - - + + - + - kinetics_479_0_ * ( k1 * S6K_thr_252_1336_0_*_40S_inact_1495_0_ - k2 * S6_phospho_cplx_1342_0_ ) + kinetics_451_0_ * ( k1 * _40S_inact_1468_0_*S6K_thr_252_1309_0_ - k2 * S6_phospho_cplx_1315_0_ ) - kinetics_479_0_ + kinetics_451_0_ k1 - S6K_thr_252_1336_0_ - _40S_inact_1495_0_ + _40S_inact_1468_0_ + S6K_thr_252_1309_0_ k2 - S6_phospho_cplx_1342_0_ + S6_phospho_cplx_1315_0_ @@ -17558,39 +18005,39 @@ - + - S6_phospho_cplx_1342_0_ - S6K_thr_252_1336_0_ - _40S_1497_0_ - S6_phospho_1341_0_ + S6_phospho_cplx_1315_0_ + S6K_thr_252_1309_0_ + _40S_1470_0_ + S6_phospho_1314_0_ 2 338.235294118 - -607.228915663 + 607.228915663 red 4 - + - - + + - kinetics_479_0_ * k3*S6_phospho_cplx_1342_0_ + kinetics_451_0_ * k3*S6_phospho_cplx_1315_0_ - kinetics_479_0_ + kinetics_451_0_ k3 - S6_phospho_cplx_1342_0_ + S6_phospho_cplx_1315_0_ @@ -17598,49 +18045,49 @@ - + - S6K_basal_1344_0_ - CaMKIII_1425_0_ - CaMKIII_basal_cplx_1347_0_ - CaMKIII_basal_1346_0_ + S6K_basal_1317_0_ + CaMKIII_1398_0_ + CaMKIII_basal_cplx_1320_0_ + CaMKIII_basal_1319_0_ 1 352.941176471 - -597.590361446 + 597.590361446 red 45 - - + + - + - kinetics_479_0_ * ( k1 * S6K_basal_1344_0_*CaMKIII_1425_0_ - k2 * CaMKIII_basal_cplx_1347_0_ ) + kinetics_451_0_ * ( k1 * S6K_basal_1317_0_*CaMKIII_1398_0_ - k2 * CaMKIII_basal_cplx_1320_0_ ) - kinetics_479_0_ + kinetics_451_0_ k1 - S6K_basal_1344_0_ - CaMKIII_1425_0_ + S6K_basal_1317_0_ + CaMKIII_1398_0_ k2 - CaMKIII_basal_cplx_1347_0_ + CaMKIII_basal_cplx_1320_0_ @@ -17651,39 +18098,39 @@ - + - CaMKIII_basal_cplx_1347_0_ - S6K_basal_1344_0_ - CaMKIII_p_1437_0_ - CaMKIII_basal_1346_0_ + CaMKIII_basal_cplx_1320_0_ + S6K_basal_1317_0_ + CaMKIII_p_1410_0_ + CaMKIII_basal_1319_0_ 2 352.941176471 - -597.590361446 + 597.590361446 red 45 - + - - + + - kinetics_479_0_ * k3*CaMKIII_basal_cplx_1347_0_ + kinetics_451_0_ * k3*CaMKIII_basal_cplx_1320_0_ - kinetics_479_0_ + kinetics_451_0_ k3 - CaMKIII_basal_cplx_1347_0_ + CaMKIII_basal_cplx_1320_0_ @@ -17691,49 +18138,49 @@ - + - CaMKIII_CaM_Ca4_1427_0_ - eEF2_1465_0_ - phospho_cplx_1430_0_ - phospho_1429_0_ + CaMKIII_CaM_Ca4_1400_0_ + eEF2_1438_0_ + phospho_cplx_1403_0_ + phospho_1402_0_ 1 14.7058823529 - -790.361445783 + 790.361445783 red 58 - - + + - + - kinetics_479_0_ * ( k1 * eEF2_1465_0_*CaMKIII_CaM_Ca4_1427_0_ - k2 * phospho_cplx_1430_0_ ) + kinetics_451_0_ * ( k1 * CaMKIII_CaM_Ca4_1400_0_*eEF2_1438_0_ - k2 * phospho_cplx_1403_0_ ) - kinetics_479_0_ + kinetics_451_0_ k1 - eEF2_1465_0_ - CaMKIII_CaM_Ca4_1427_0_ + CaMKIII_CaM_Ca4_1400_0_ + eEF2_1438_0_ k2 - phospho_cplx_1430_0_ + phospho_cplx_1403_0_ @@ -17744,39 +18191,39 @@ - + - phospho_cplx_1430_0_ - CaMKIII_CaM_Ca4_1427_0_ - eEFthr_56_1467_0_ - phospho_1429_0_ + phospho_cplx_1403_0_ + CaMKIII_CaM_Ca4_1400_0_ + eEFthr_56_1440_0_ + phospho_1402_0_ 2 14.7058823529 - -790.361445783 + 790.361445783 red 58 - + - - + + - kinetics_479_0_ * k3*phospho_cplx_1430_0_ + kinetics_451_0_ * k3*phospho_cplx_1403_0_ - kinetics_479_0_ + kinetics_451_0_ k3 - phospho_cplx_1430_0_ + phospho_cplx_1403_0_ @@ -17784,49 +18231,49 @@ - + - CaMKIII_basal_1432_0_ - eEF2_1465_0_ - eEF2thr56_basal_cplx_1435_0_ - eEF2thr56_basal_1434_0_ + CaMKIII_basal_1405_0_ + eEF2_1438_0_ + eEF2thr56_basal_cplx_1408_0_ + eEF2thr56_basal_1407_0_ 1 29.4117647059 - -790.361445783 + 790.361445783 red 45 - - + + - + - kinetics_479_0_ * ( k1 * CaMKIII_basal_1432_0_*eEF2_1465_0_ - k2 * eEF2thr56_basal_cplx_1435_0_ ) + kinetics_451_0_ * ( k1 * CaMKIII_basal_1405_0_*eEF2_1438_0_ - k2 * eEF2thr56_basal_cplx_1408_0_ ) - kinetics_479_0_ + kinetics_451_0_ k1 - CaMKIII_basal_1432_0_ - eEF2_1465_0_ + CaMKIII_basal_1405_0_ + eEF2_1438_0_ k2 - eEF2thr56_basal_cplx_1435_0_ + eEF2thr56_basal_cplx_1408_0_ @@ -17837,39 +18284,39 @@ - + - eEF2thr56_basal_cplx_1435_0_ - CaMKIII_basal_1432_0_ - eEFthr_56_1467_0_ - eEF2thr56_basal_1434_0_ + eEF2thr56_basal_cplx_1408_0_ + CaMKIII_basal_1405_0_ + eEFthr_56_1440_0_ + eEF2thr56_basal_1407_0_ 2 29.4117647059 - -790.361445783 + 790.361445783 red 45 - + - - + + - kinetics_479_0_ * k3*eEF2thr56_basal_cplx_1435_0_ + kinetics_451_0_ * k3*eEF2thr56_basal_cplx_1408_0_ - kinetics_479_0_ + kinetics_451_0_ k3 - eEF2thr56_basal_cplx_1435_0_ + eEF2thr56_basal_cplx_1408_0_ @@ -17877,49 +18324,49 @@ - + - Translation_clx_1471_0_ - AA_1393_0_ - pro_syn_cplx_1474_0_ - pro_syn_1473_0_ + Translation_clx_1444_0_ + AA_1366_0_ + pro_syn_cplx_1447_0_ + pro_syn_1446_0_ 1 338.235294118 - -790.361445783 + 790.361445783 red 52 - - + + - + - kinetics_479_0_ * ( k1 * AA_1393_0_*Translation_clx_1471_0_ - k2 * pro_syn_cplx_1474_0_ ) + kinetics_451_0_ * ( k1 * Translation_clx_1444_0_*AA_1366_0_ - k2 * pro_syn_cplx_1447_0_ ) - kinetics_479_0_ + kinetics_451_0_ k1 - AA_1393_0_ - Translation_clx_1471_0_ + Translation_clx_1444_0_ + AA_1366_0_ k2 - pro_syn_cplx_1474_0_ + pro_syn_cplx_1447_0_ @@ -17930,39 +18377,39 @@ - + - pro_syn_cplx_1474_0_ - Translation_clx_1471_0_ - peptide_1395_0_ - pro_syn_1473_0_ + pro_syn_cplx_1447_0_ + Translation_clx_1444_0_ + peptide_1368_0_ + pro_syn_1446_0_ 2 338.235294118 - -790.361445783 + 790.361445783 red 52 - + - - + + - kinetics_479_0_ * k3*pro_syn_cplx_1474_0_ + kinetics_451_0_ * k3*pro_syn_cplx_1447_0_ - kinetics_479_0_ + kinetics_451_0_ k3 - pro_syn_cplx_1474_0_ + pro_syn_cplx_1447_0_ @@ -17970,49 +18417,49 @@ - + - Translation_clx_1471_0_ - rad_AA_1401_0_ - rad_pro_syn_cplx_1477_0_ - rad_pro_syn_1476_0_ + Translation_clx_1444_0_ + rad_AA_1374_0_ + rad_pro_syn_cplx_1450_0_ + rad_pro_syn_1449_0_ 1 338.235294118 - -800.0 + 800.0 red 52 - - + + - + - kinetics_479_0_ * ( k1 * rad_AA_1401_0_*Translation_clx_1471_0_ - k2 * rad_pro_syn_cplx_1477_0_ ) + kinetics_451_0_ * ( k1 * Translation_clx_1444_0_*rad_AA_1374_0_ - k2 * rad_pro_syn_cplx_1450_0_ ) - kinetics_479_0_ + kinetics_451_0_ k1 - rad_AA_1401_0_ - Translation_clx_1471_0_ + Translation_clx_1444_0_ + rad_AA_1374_0_ k2 - rad_pro_syn_cplx_1477_0_ + rad_pro_syn_cplx_1450_0_ @@ -18023,39 +18470,39 @@ - + - rad_pro_syn_cplx_1477_0_ - Translation_clx_1471_0_ - rad_peptide_1403_0_ - rad_pro_syn_1476_0_ + rad_pro_syn_cplx_1450_0_ + Translation_clx_1444_0_ + rad_peptide_1376_0_ + rad_pro_syn_1449_0_ 2 338.235294118 - -800.0 + 800.0 red 52 - + - - + + - kinetics_479_0_ * k3*rad_pro_syn_cplx_1477_0_ + kinetics_451_0_ * k3*rad_pro_syn_cplx_1450_0_ - kinetics_479_0_ + kinetics_451_0_ k3 - rad_pro_syn_cplx_1477_0_ + rad_pro_syn_cplx_1450_0_ @@ -18063,49 +18510,49 @@ - + - Basal_Translation_1481_0_ - AA_1393_0_ - basal_syn_cplx_1484_0_ - basal_syn_1483_0_ + Basal_Translation_1454_0_ + AA_1366_0_ + basal_syn_cplx_1457_0_ + basal_syn_1456_0_ 1 367.647058824 - -790.361445783 + 790.361445783 red 53 - - + + - + - kinetics_479_0_ * ( k1 * Basal_Translation_1481_0_*AA_1393_0_ - k2 * basal_syn_cplx_1484_0_ ) + kinetics_451_0_ * ( k1 * AA_1366_0_*Basal_Translation_1454_0_ - k2 * basal_syn_cplx_1457_0_ ) - kinetics_479_0_ + kinetics_451_0_ k1 - Basal_Translation_1481_0_ - AA_1393_0_ + AA_1366_0_ + Basal_Translation_1454_0_ k2 - basal_syn_cplx_1484_0_ + basal_syn_cplx_1457_0_ @@ -18116,39 +18563,39 @@ - + - basal_syn_cplx_1484_0_ - Basal_Translation_1481_0_ - peptide_1395_0_ - basal_syn_1483_0_ + basal_syn_cplx_1457_0_ + Basal_Translation_1454_0_ + peptide_1368_0_ + basal_syn_1456_0_ 2 367.647058824 - -790.361445783 + 790.361445783 red 53 - + - - + + - kinetics_479_0_ * k3*basal_syn_cplx_1484_0_ + kinetics_451_0_ * k3*basal_syn_cplx_1457_0_ - kinetics_479_0_ + kinetics_451_0_ k3 - basal_syn_cplx_1484_0_ + basal_syn_cplx_1457_0_ @@ -18156,49 +18603,49 @@ - + - Basal_Translation_1481_0_ - rad_AA_1401_0_ - rad_basal_syn_cplx_1487_0_ - rad_basal_syn_1486_0_ + Basal_Translation_1454_0_ + rad_AA_1374_0_ + rad_basal_syn_cplx_1460_0_ + rad_basal_syn_1459_0_ 1 367.647058824 - -800.0 + 800.0 red 53 - - + + - + - kinetics_479_0_ * ( k1 * Basal_Translation_1481_0_*rad_AA_1401_0_ - k2 * rad_basal_syn_cplx_1487_0_ ) + kinetics_451_0_ * ( k1 * rad_AA_1374_0_*Basal_Translation_1454_0_ - k2 * rad_basal_syn_cplx_1460_0_ ) - kinetics_479_0_ + kinetics_451_0_ k1 - Basal_Translation_1481_0_ - rad_AA_1401_0_ + rad_AA_1374_0_ + Basal_Translation_1454_0_ k2 - rad_basal_syn_cplx_1487_0_ + rad_basal_syn_cplx_1460_0_ @@ -18209,39 +18656,39 @@ - + - rad_basal_syn_cplx_1487_0_ - Basal_Translation_1481_0_ - peptide_1395_0_ - rad_basal_syn_1486_0_ + rad_basal_syn_cplx_1460_0_ + Basal_Translation_1454_0_ + peptide_1368_0_ + rad_basal_syn_1459_0_ 2 367.647058824 - -800.0 + 800.0 red 53 - + - - + + - kinetics_479_0_ * k3*rad_basal_syn_cplx_1487_0_ + kinetics_451_0_ * k3*rad_basal_syn_cplx_1460_0_ - kinetics_479_0_ + kinetics_451_0_ k3 - rad_basal_syn_cplx_1487_0_ + rad_basal_syn_cplx_1460_0_ @@ -18249,49 +18696,49 @@ - + - _40S_basal_1499_0_ - _40S_inact_1495_0_ - basal_cplx_1502_0_ - basal_1501_0_ + _40S_basal_1472_0_ + _40S_inact_1468_0_ + basal_cplx_1475_0_ + basal_1474_0_ 1 470.588235294 - -790.361445783 + 790.361445783 red 44 - - + + - + - kinetics_479_0_ * ( k1 * _40S_basal_1499_0_*_40S_inact_1495_0_ - k2 * basal_cplx_1502_0_ ) + kinetics_451_0_ * ( k1 * _40S_basal_1472_0_*_40S_inact_1468_0_ - k2 * basal_cplx_1475_0_ ) - kinetics_479_0_ + kinetics_451_0_ k1 - _40S_basal_1499_0_ - _40S_inact_1495_0_ + _40S_basal_1472_0_ + _40S_inact_1468_0_ k2 - basal_cplx_1502_0_ + basal_cplx_1475_0_ @@ -18302,39 +18749,39 @@ - + - basal_cplx_1502_0_ - _40S_basal_1499_0_ - _40S_1497_0_ - basal_1501_0_ + basal_cplx_1475_0_ + _40S_basal_1472_0_ + _40S_1470_0_ + basal_1474_0_ 2 470.588235294 - -790.361445783 + 790.361445783 red 44 - + - - + + - kinetics_479_0_ * k3*basal_cplx_1502_0_ + kinetics_451_0_ * k3*basal_cplx_1475_0_ - kinetics_479_0_ + kinetics_451_0_ k3 - basal_cplx_1502_0_ + basal_cplx_1475_0_ @@ -18342,49 +18789,49 @@ - + - TSC1_TSC2_1508_0_ - Rheb_GTP_1304_0_ - TSC2phospho_cplx_1511_0_ - TSC2phospho_1510_0_ + TSC1_TSC2_1481_0_ + Rheb_GTP_1277_0_ + TSC2phospho_cplx_1484_0_ + TSC2phospho_1483_0_ 1 602.941176471 - -790.361445783 + 790.361445783 red 51 - - + + - + - kinetics_479_0_ * ( k1 * Rheb_GTP_1304_0_*TSC1_TSC2_1508_0_ - k2 * TSC2phospho_cplx_1511_0_ ) + kinetics_451_0_ * ( k1 * TSC1_TSC2_1481_0_*Rheb_GTP_1277_0_ - k2 * TSC2phospho_cplx_1484_0_ ) - kinetics_479_0_ + kinetics_451_0_ k1 - Rheb_GTP_1304_0_ - TSC1_TSC2_1508_0_ + TSC1_TSC2_1481_0_ + Rheb_GTP_1277_0_ k2 - TSC2phospho_cplx_1511_0_ + TSC2phospho_cplx_1484_0_ @@ -18395,39 +18842,39 @@ - + - TSC2phospho_cplx_1511_0_ - TSC1_TSC2_1508_0_ - Rheb_GDP_1306_0_ - TSC2phospho_1510_0_ + TSC2phospho_cplx_1484_0_ + TSC1_TSC2_1481_0_ + Rheb_GDP_1279_0_ + TSC2phospho_1483_0_ 2 602.941176471 - -790.361445783 + 790.361445783 red 51 - + - - + + - kinetics_479_0_ * k3*TSC2phospho_cplx_1511_0_ + kinetics_451_0_ * k3*TSC2phospho_cplx_1484_0_ - kinetics_479_0_ + kinetics_451_0_ k3 - TSC2phospho_cplx_1511_0_ + TSC2phospho_cplx_1484_0_ @@ -18435,49 +18882,49 @@ - + - L_dot_mGluR_p_dot_Homer_dot_PIKE_L_dot_PI3K_1525_0_ - PIP2_636_0_ - Enz_cplx_1528_0_ - Enz_1527_0_ + L_dot_mGluR_p_dot_Homer_dot_PIKE_L_dot_PI3K_1498_0_ + PIP2_609_0_ + Enz_cplx_1501_0_ + Enz_1500_0_ 1 794.117647059 - -790.361445783 + 790.361445783 27 23 - - + + - + - kinetics_479_0_ * ( k1 * PIP2_636_0_*L_dot_mGluR_p_dot_Homer_dot_PIKE_L_dot_PI3K_1525_0_ - k2 * Enz_cplx_1528_0_ ) + kinetics_451_0_ * ( k1 * PIP2_609_0_*L_dot_mGluR_p_dot_Homer_dot_PIKE_L_dot_PI3K_1498_0_ - k2 * Enz_cplx_1501_0_ ) - kinetics_479_0_ + kinetics_451_0_ k1 - PIP2_636_0_ - L_dot_mGluR_p_dot_Homer_dot_PIKE_L_dot_PI3K_1525_0_ + PIP2_609_0_ + L_dot_mGluR_p_dot_Homer_dot_PIKE_L_dot_PI3K_1498_0_ k2 - Enz_cplx_1528_0_ + Enz_cplx_1501_0_ @@ -18488,39 +18935,39 @@ - + - Enz_cplx_1528_0_ - L_dot_mGluR_p_dot_Homer_dot_PIKE_L_dot_PI3K_1525_0_ - PIP3_1203_0_ - Enz_1527_0_ + Enz_cplx_1501_0_ + L_dot_mGluR_p_dot_Homer_dot_PIKE_L_dot_PI3K_1498_0_ + PIP3_1176_0_ + Enz_1500_0_ 2 794.117647059 - -790.361445783 + 790.361445783 27 23 - + - - + + - kinetics_479_0_ * k3*Enz_cplx_1528_0_ + kinetics_451_0_ * k3*Enz_cplx_1501_0_ - kinetics_479_0_ + kinetics_451_0_ k3 - Enz_cplx_1528_0_ + Enz_cplx_1501_0_ @@ -18528,49 +18975,49 @@ - + - GRK_1538_0_ - Rec_Glu_1093_0_ - GRK_binding_cplx_1541_0_ - GRK_binding_1540_0_ + GRK_1511_0_ + Rec_Glu_1066_0_ + GRK_binding_cplx_1514_0_ + GRK_binding_1513_0_ 1 882.352941176 - -790.361445783 + 790.361445783 20 black - - + + - + - kinetics_479_0_ * ( k1 * GRK_1538_0_*Rec_Glu_1093_0_ - k2 * GRK_binding_cplx_1541_0_ ) + kinetics_451_0_ * ( k1 * Rec_Glu_1066_0_*GRK_1511_0_ - k2 * GRK_binding_cplx_1514_0_ ) - kinetics_479_0_ + kinetics_451_0_ k1 - GRK_1538_0_ - Rec_Glu_1093_0_ + Rec_Glu_1066_0_ + GRK_1511_0_ k2 - GRK_binding_cplx_1541_0_ + GRK_binding_cplx_1514_0_ @@ -18581,39 +19028,39 @@ - + - GRK_binding_cplx_1541_0_ - GRK_1538_0_ - L_dot_mGluR_p_1543_0_ - GRK_binding_1540_0_ + GRK_binding_cplx_1514_0_ + GRK_1511_0_ + L_dot_mGluR_p_1516_0_ + GRK_binding_1513_0_ 2 882.352941176 - -790.361445783 + 790.361445783 20 black - + - - + + - kinetics_479_0_ * k3*GRK_binding_cplx_1541_0_ + kinetics_451_0_ * k3*GRK_binding_cplx_1514_0_ - kinetics_479_0_ + kinetics_451_0_ k3 - GRK_binding_cplx_1541_0_ + GRK_binding_cplx_1514_0_ @@ -18623,7 +19070,7 @@ - + kinetics @@ -18631,37 +19078,37 @@ - - - - - - - - - - - - - - - - - - - - - - - - - - - - + + + + + + + + + + + + + + + + + + + + + + + + + + + + - + kinetics @@ -18669,185 +19116,177 @@ - - - - - - - - - - - - - - - - - - - - - + + + + + + + + + + + + + + + + + + + + + - + kinetics - 6 + 23 - - - - - - - - + + + + + + + + + + + - + kinetics - 23 + 6 - - - - - - - - - - - + + + + + + + + - + kinetics - 4 + 10 - - - - - - - - - - - - - - - - - - - - - - - - + + + + + + + + + + + + + + + + + + + + + - + kinetics - 12 + 15 - - - - - - - - - - + + + + + + + + + + - + kinetics - 11 + 16 - - - - - - - - - - - - + + + + + + + + - + kinetics - 16 + 27 - - - - - - - - + - + kinetics - 20 + 2 - - - - - - - - - - - - + + + + + + + + + + + + + + + + + + - + kinetics @@ -18855,319 +19294,310 @@ - - - - - - - - - - - - + + + + + + + + + + + + - + kinetics - 14 + 9 - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - + + + + + + + + + + + + + + + - + kinetics - 32 + 4 - - - - + + + + + + + + + + + + + + + + + + + + + + + + - + kinetics - 15 + 8 - - - - - - - - - - + + + + + + + + + + + + - + kinetics - 34 + 33 - - - - - - - - - - - - - - + + + + + + + + + - + kinetics - 19 + 26 - - - - - - - - - - - - - - - - - - - + + + + + + + + + + + + + - + kinetics - 30 + 22 - - - - - - - - - - - - + + + + + + + + + - + kinetics - 13 + 24 - - - - - - - - - - - - - - - - - - - - + + + + + + + + + - + kinetics - 18 + 28 - + + + + + + + - + kinetics - 29 + 31 - - - - - - - - - - + + + + - + kinetics - 10 + 12 - - - - - - - - - - - - - - - - - - - - - + + + + + + + + + + - + kinetics - 17 + 11 - - - - - - - - - - - - - - - - - - - - - - - + + + + + + + + + + + + - + kinetics - 27 + 17 - + + + + + + + + + + + + + + + + + + + + + + + - + kinetics - 3 + 20 - - - + + + + + + + + + + + + - + kinetics @@ -19175,257 +19605,274 @@ - - - - - - - - - - - - - - - - - - - - - + + + + + + + + + + + + + + + + + + + + + - + kinetics - 8 + 7 - - - - - - - - - - - - + + + + + + + + + + + + + + + + - + kinetics - 31 + 14 - - - - + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + - + kinetics - 33 + 25 - - - - - - - - - + + + + + + + + - + kinetics - 26 + 3 - - - - - - - - - - - - - + + + - + kinetics - 22 + 18 - - - - - - - - - + - + kinetics - 2 + 19 - - - - - - - - - - - - - - - - - - + + + + + + + + + + + + + + + + + + + - + kinetics - 24 + 34 - - - - - - - - - + + + + + + + + + + + + + + - + kinetics - 28 + 32 - - - - - - - + + + + - + kinetics - 9 + 29 - - - - - - - - - - - - - - - + + + + + + + + + + - + kinetics - 7 + 13 - - - - - - - - - - - - - - - - + + + + + + + + + + + + + + + + + + + + - + kinetics - 25 + 30 - - - - - - - - + + + + + + + + + + + +