238442
stoichiometry: 1.0
species: 966130
type: SpeciesReference

237316
stoichiometry: 1.0
species: 965411
type: SpeciesReference

233100
stoichiometry: 1.0
species: 966430
type: SpeciesReference

230698
stoichiometry: 1.0
species: 964081
type: SpeciesReference

964600
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

509680
units: 230126
value: 1.0E-11
type: LocalParameter

510084
units: 230211
value: 3.96E-12
type: LocalParameter

965970
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

965272
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

969070
kinetic law: 234248
product: 234236
product: 234224
reactant: 234212
fast: false
reversible: false
type: Reaction

969970
kinetic law: 236470
product: 236458
reactant: 236446
reactant: 236434
notes: 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
fast: false
reversible: true
type: Reaction

964381
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

965930
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

236519
local parameters: 509993
notes: k3*Ras_slash_GEF_minus_Gprot_minus_bg_slash_GEF_minus_bg_act_minus_ras_slash_GEF_minus_bg_act_minus_ras_cplx
type: KineticLaw

230404
local parameters: 509595
local parameters: 509594
notes: kf*PKC_slash_PKC_minus_Ca-kb*PKC_slash_PKC_minus_Ca_minus_memb_star_
type: KineticLaw

969090
kinetic law: 234296
product: 234284
reactant: 234272
reactant: 234260
notes: Rates are 60% those of PKC-phosph-neurogranin. See Huang et al ABB 305:2 570-580 1993
fast: false
reversible: true
type: Reaction

235662
stoichiometry: 1.0
species: 964680
type: SpeciesReference

237027
stoichiometry: 1.0
species: 965275
type: SpeciesReference

236603
stoichiometry: 1.0
species: 965120
type: SpeciesReference

964361
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

966490
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

966690
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.02
initial amount: NaN
in compartment: 963861
type: Species

965160
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

510064
units: 230126
value: 1.4E-12
type: LocalParameter

966750
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.015
initial amount: NaN
in compartment: 963861
type: Species

231462
stoichiometry: 1.0
species: 964540
type: SpeciesReference

509756
units: 230126
value: 1.0E-13
type: LocalParameter

231123
stoichiometry: 1.0
species: 964121
type: SpeciesReference

233634
local parameters: 509876
local parameters: 509874
notes: kf*AC_slash_AC2_star_-kb*AC_slash_AC2
type: KineticLaw

232323
local parameters: 509764
local parameters: 509762
notes: kf*Sos_slash_Sos_star_-kb*Sos_slash_Sos
type: KineticLaw

965120
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

510083
units: 230126
value: 6.0E-12
type: LocalParameter

966650
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

238152
stoichiometry: 1.0
species: 965950
type: SpeciesReference

232846
stoichiometry: 1.0
species: 966050
type: SpeciesReference

966450
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

237401
stoichiometry: 1.0
species: 967110
type: SpeciesReference

238357
stoichiometry: 1.0
species: 965710
type: SpeciesReference

231911
local parameters: 509724
local parameters: 509722
notes: kf*Ras_slash_GEF_star_-kb*Ras_slash_inact_minus_GEF
type: KineticLaw

967830
kinetic law: 231341
product: 231329
reactant: 231317
reactant: 231305
notes: 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.
fast: false
reversible: true
type: Reaction

964640
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

235599
local parameters: 509962
local parameters: 509961
notes: k1*MAPK_slash_MAPK_minus_tyr*MAPK_slash_MAPKK_star_-k2*MAPK_slash_MAPKK_star__slash_MAPKKthr_slash_MAPKKthr_cplx
type: KineticLaw

232665
stoichiometry: 2.0
species: 967190
type: SpeciesReference

509640
units: 230126
value: 0.0
type: LocalParameter

969930
kinetic law: 236372
product: 236360
reactant: 236348
reactant: 236336
notes: 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.
fast: false
reversible: true
type: Reaction

969470
kinetic law: 235226
product: 235214
product: 235202
reactant: 235189
fast: false
reversible: false
type: Reaction

969670
kinetic law: 235748
product: 235736
product: 235724
reactant: 235712
fast: false
reversible: false
type: Reaction

510067
units: 230211
value: 3.432E-13
type: LocalParameter

509730
units: 230126
value: 1.0E-13
type: LocalParameter

969050
kinetic law: 234200
product: 234188
reactant: 234176
reactant: 234164
notes: Rates from Huang et al ABB 305:2 570-580 1993
fast: false
reversible: true
type: Reaction

964440
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

237741
stoichiometry: 1.0
species: 965870
type: SpeciesReference

510086
units: 230126
value: 6.0E-12
type: LocalParameter

234020
stoichiometry: 1.0
species: 964181
type: SpeciesReference

969870
kinetic law: 236228
product: 236216
product: 236204
reactant: 236192
fast: false
reversible: false
type: Reaction

970170
kinetic law: 236954
product: 236942
reactant: 236930
reactant: 236918
notes: #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.
fast: false
reversible: true
type: Reaction

965060
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

237657
local parameters: 510040
local parameters: 510039
notes: k1*CaMKII_slash_CaMKII_minus_CaM*CaMKII_slash_tot_CaM_CaMKII-k2*CaMKII_slash_tot_CaM_CaMKII_slash_CaM_act_286_slash_CaM_act_286_cplx
type: KineticLaw

232044
stoichiometry: 1.0
species: 965260
type: SpeciesReference

231862
stoichiometry: 1.0
species: 965060
type: SpeciesReference

239485
stoichiometry: 1.0
species: 966910
type: SpeciesReference

234694
local parameters: 509929
local parameters: 509928
notes: k1*PLA2_slash_APC*PLA2_slash_PIP2_minus_Ca_minus_PLA2_star_-k2*PLA2_slash_PIP2_minus_Ca_minus_PLA2_star__slash_kenz_slash_kenz_cplx
type: KineticLaw

234333
stoichiometry: 1.0
species: 966050
type: SpeciesReference

234779
stoichiometry: 1.0
species: 964380
type: SpeciesReference

231510
stoichiometry: 1.0
species: 964560
type: SpeciesReference

970150
kinetic law: 236906
product: 236894
product: 236882
reactant: 236870
fast: false
reversible: false
type: Reaction

236663
local parameters: 509998
local parameters: 509997
notes: k1*Ras_slash_GTP_minus_Ras*Ras_slash_GAP-k2*Ras_slash_GAP_slash_GAP_minus_inact_minus_ras_slash_GAP_minus_inact_minus_ras_cplx
type: KineticLaw

969890
kinetic law: 236276
product: 236264
reactant: 236252
reactant: 236240
fast: false
reversible: true
type: Reaction

230723
stoichiometry: 1.0
species: 964281
type: SpeciesReference

231717
stoichiometry: 1.0
species: 964600
type: SpeciesReference

230477
stoichiometry: 1.0
species: 963941
type: SpeciesReference

236348
stoichiometry: 1.0
species: 964960
type: SpeciesReference

970790
kinetic law: 238479
product: 238467
product: 238455
reactant: 238442
fast: false
reversible: false
type: Reaction

969030
kinetic law: 234152
product: 234140
product: 234128
reactant: 234116
fast: false
reversible: false
type: Reaction

510087
units: 230211
value: 3.42E-14
type: LocalParameter

230941
local parameters: 509640
local parameters: 509638
notes: kf*AA-kb*PLA2_slash_APC
type: KineticLaw

509758
units: 230211
value: 2.50002E-14
type: LocalParameter

964441
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

231802
stoichiometry: 1.0
species: 965160
type: SpeciesReference

510066
units: 230126
value: 3.5E-13
type: LocalParameter

510085
units: 230126
value: 2.5E-11
type: LocalParameter

965275
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

238988
stoichiometry: 1.0
species: 966650
type: SpeciesReference

232383
stoichiometry: 1.0
species: 965630
type: SpeciesReference

964401
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

232505
local parameters: 509780
local parameters: 509778
notes: kf*PLC_g_slash_Ca_dot_PLC_g_star_-kb*PLC_g_slash_Ca_dot_PLC_g
type: KineticLaw

970750
kinetic law: 238381
product: 238369
product: 238357
reactant: 238345
fast: false
reversible: false
type: Reaction

235539
stoichiometry: 1.0
species: 964740
type: SpeciesReference

238589
stoichiometry: 1.0
species: 966230
type: SpeciesReference

966410
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

230783
stoichiometry: 1.0
species: 964281
type: SpeciesReference

969010
kinetic law: 234104
product: 234092
reactant: 234080
reactant: 234068
notes: 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
fast: false
reversible: true
type: Reaction

231050
stoichiometry: 1.0
species: 964480
type: SpeciesReference

233259
local parameters: 509844
local parameters: 509842
notes: kf*PKA_slash_R2C2*cAMP-kb*PKA_slash_R2C2_minus_cAMP
type: KineticLaw

236300
stoichiometry: 1.0
species: 964680
type: SpeciesReference

236711
local parameters: 509999
notes: k3*Ras_slash_GAP_slash_GAP_minus_inact_minus_ras_slash_GAP_minus_inact_minus_ras_cplx
type: KineticLaw

239206
local parameters: 510109
local parameters: 510107
notes: kcat*AC_slash_AC2_star__minus_Gs*AC_slash_ATP/(Km+AC_slash_ATP)
type: KineticLaw

231208
stoichiometry: 1.0
species: 964501
type: SpeciesReference

967370
kinetic law: 230320
product: 230308
reactant: 230295
reactant: 230283
notes: 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
fast: false
reversible: true
type: Reaction

963981
constant: false
boundary condition: false
has only substance units: false
initial concentration: 9.43516666666667E-21
initial amount: NaN
in compartment: 963861
type: Species

968510
kinetic law: 232870
product: 232858
reactant: 232846
notes: 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.
fast: false
reversible: true
type: Reaction

236627
stoichiometry: 1.0
species: 965160
type: SpeciesReference

968390
kinetic law: 232604
product: 232591
reactant: 232579
reactant: 232567
notes: 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
fast: false
reversible: true
type: Reaction

509732
units: 230126
value: 0.0
type: LocalParameter

231668
stoichiometry: 1.0
species: 964581
type: SpeciesReference

509965
units: 230126
value: 4.2E-13
type: LocalParameter

235772
stoichiometry: 1.0
species: 964840
type: SpeciesReference

232104
stoichiometry: 1.0
species: 965411
type: SpeciesReference

237705
local parameters: 510041
notes: k3*CaMKII_slash_tot_CaM_CaMKII_slash_CaM_act_286_slash_CaM_act_286_cplx
type: KineticLaw

509966
units: 230126
value: 1.05E-13
type: LocalParameter

968790
kinetic law: 233598
product: 233586
reactant: 233574
reactant: 233562
notes: 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
fast: false
reversible: true
type: Reaction

239375
stoichiometry: 1.0
species: 966790
type: SpeciesReference

230674
stoichiometry: 1.0
species: 964061
type: SpeciesReference

509752
units: 230126
value: 3.3E-16
type: LocalParameter

510089
units: 230126
value: 3.4E-14
type: LocalParameter

233960
local parameters: 509902
notes: k3*PKC_minus_active_slash_PKC_minus_act_minus_raf_slash_PKC_minus_act_minus_raf_cplx
type: KineticLaw

232468
local parameters: 509776
local parameters: 509774
notes: kf*Ca*PLC_g_slash_PLC_G_star_-kb*PLC_g_slash_Ca_dot_PLC_g_star_
type: KineticLaw

232737
local parameters: 509800
local parameters: 509798
notes: kf*CaM_minus_TR2_minus_Ca2*Ca-kb*CaM_minus_Ca3
type: KineticLaw

234730
stoichiometry: 1.0
species: 964341
type: SpeciesReference

233743
stoichiometry: 1.0
species: 966990
type: SpeciesReference

235575
stoichiometry: 1.0
species: 964740
type: SpeciesReference

232641
local parameters: 509792
local parameters: 509790
notes: kf*CaMKII_slash_CaMKII-kb*CaMKII_slash_CaMKII_minus_thr286
type: KineticLaw

235700
local parameters: 509965
local parameters: 509964
notes: k1*MAPK_slash_MAPKK*MAPK_slash_Raf_minus_GTP_minus_Ras_star_-k2*MAPK_slash_Raf_minus_GTP_minus_Ras_star__slash_Raf_minus_GTP_minus_Ras_star__dot_1_slash_Raf_minus_GTP_minus_Ras_star__dot_1_cplx
type: KineticLaw

965411
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

970690
kinetic law: 238236
product: 238224
reactant: 238212
reactant: 238200
fast: false
reversible: true
type: Reaction

233659
stoichiometry: 1.0
species: 966990
type: SpeciesReference

238467
stoichiometry: 1.0
species: 967270
type: SpeciesReference

509967
units: 230211
value: 3.3E-12
type: LocalParameter

232822
stoichiometry: 1.0
species: 966030
type: SpeciesReference

510088
units: 230126
value: 1.36E-13
type: LocalParameter

968590
kinetic law: 233112
product: 233100
reactant: 233088
reactant: 233076
notes: Disabled. See notes for PP2B7.g
fast: false
reversible: true
type: Reaction

239073
stoichiometry: 1.0
species: 967170
type: SpeciesReference

970670
kinetic law: 238188
product: 238176
product: 238164
reactant: 238152
fast: false
reversible: false
type: Reaction

967110
constant: true
boundary condition: true
has only substance units: false
initial concentration: 10.0
initial amount: NaN
in compartment: 963861
type: Species

239460
stoichiometry: 1.0
species: 966930
type: SpeciesReference

509940
units: 230211
value: 3.9E-12
type: LocalParameter

235688
stoichiometry: 1.0
species: 964860
type: SpeciesReference

968410
kinetic law: 232641
product: 232628
reactant: 232616
notes: 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.
fast: false
reversible: true
type: Reaction

238552
stoichiometry: 1.0
species: 966190
type: SpeciesReference

970610
kinetic law: 238044
product: 238032
reactant: 238020
reactant: 238008
fast: false
reversible: true
type: Reaction

232080
stoichiometry: 1.0
species: 965390
type: SpeciesReference

237220
stoichiometry: 1.0
species: 965411
type: SpeciesReference

509734
units: 230211
value: 6.0E-11
type: LocalParameter

230965
stoichiometry: 1.0
species: 967190
type: SpeciesReference

234851
stoichiometry: 1.0
species: 967010
type: SpeciesReference

509754
units: 230211
value: 4.9998E-13
type: LocalParameter

509968
units: 230126
value: 4.2E-13
type: LocalParameter

234044
stoichiometry: 1.0
species: 967210
type: SpeciesReference

510062
units: 230211
value: 3.432E-13
type: LocalParameter

239279
stoichiometry: 1.0
species: 966790
type: SpeciesReference

970810
kinetic law: 238527
product: 238515
reactant: 238503
reactant: 238491
fast: false
reversible: true
type: Reaction

510109
units: 230090
value: 60.0
type: LocalParameter

967850
kinetic law: 231389
product: 231377
reactant: 231365
reactant: 231353
notes: 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/#
fast: false
reversible: true
type: Reaction

230747
stoichiometry: 1.0
species: 964301
type: SpeciesReference

232020
stoichiometry: 1.0
species: 965263
type: SpeciesReference

237426
stoichiometry: 1.0
species: 964461
type: SpeciesReference

235153
stoichiometry: 1.0
species: 964421
type: SpeciesReference

234357
local parameters: 509918
notes: k3*PKC_minus_active_slash_PKC_minus_phosph_minus_ng_minus_CaM_slash_PKC_minus_phosph_minus_ng_minus_CaM_cplx
type: KineticLaw

966730
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

238565
stoichiometry: 1.0
species: 967270
type: SpeciesReference

233235
stoichiometry: 1.0
species: 966650
type: SpeciesReference

237583
stoichiometry: 1.0
species: 965770
type: SpeciesReference

230320
local parameters: 509591
local parameters: 509590
notes: kf*PKC_slash_PKC_minus_cytosolic*Ca-kb*PKC_slash_PKC_minus_Ca
type: KineticLaw

231074
local parameters: 509652
local parameters: 509650
notes: kf*Ca*PLCbeta_slash_PLC-kb*PLCbeta_slash_PLC_minus_Ca
type: KineticLaw

231826
local parameters: 509716
local parameters: 509714
notes: kf*MAPK_slash_craf_minus_1_star_*Ras_slash_GTP_minus_Ras-kb*MAPK_slash_Raf_minus_GTP_minus_Ras_star_
type: KineticLaw

968450
kinetic law: 232737
product: 232725
reactant: 232713
reactant: 232701
notes: 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
fast: false
reversible: true
type: Reaction

233586
stoichiometry: 1.0
species: 966670
type: SpeciesReference

510061
units: 230126
value: 3.5E-13
type: LocalParameter

509969
units: 230126
value: 1.05E-13
type: LocalParameter

238964
local parameters: 510089
notes: k3*CaNAB_minus_Ca4_slash_dephosph_inhib1_noCaM_slash_dephosph_inhib1_noCaM_cplx
type: KineticLaw

237632
stoichiometry: 1.0
species: 967230
type: SpeciesReference

236252
stoichiometry: 1.0
species: 964960
type: SpeciesReference

233161
local parameters: 509836
local parameters: 509834
notes: kf*CaM_minus_Ca3*CaNAB_minus_Ca4-kb*PP2B_slash_CaMCa3_minus_CaNAB
type: KineticLaw

964360
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

964420
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

235264
stoichiometry: 1.0
species: 964500
type: SpeciesReference

969950
kinetic law: 236421
product: 236409
product: 236397
reactant: 236385
fast: false
reversible: false
type: Reaction

234621
stoichiometry: 1.0
species: 964141
type: SpeciesReference

510107
units: 230126
value: 5.4E-11
type: LocalParameter

969450
kinetic law: 235177
product: 235165
reactant: 235153
reactant: 235141
notes: 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.
fast: false
reversible: true
type: Reaction

509981
units: 230126
value: 6.0E-12
type: LocalParameter

509660
units: 230126
value: 0.0
type: LocalParameter

234116
stoichiometry: 1.0
species: 964201
type: SpeciesReference

232797
stoichiometry: 1.0
species: 966070
type: SpeciesReference

509961
units: 230211
value: 1.62E-11
type: LocalParameter

232991
stoichiometry: 1.0
species: 966390
type: SpeciesReference

235724
stoichiometry: 1.0
species: 964820
type: SpeciesReference

239424
stoichiometry: 1.0
species: 966910
type: SpeciesReference

509905
units: 230126
value: 1.6E-11
type: LocalParameter

233767
stoichiometry: 1.0
species: 966810
type: SpeciesReference

231317
stoichiometry: 1.0
species: 964521
type: SpeciesReference

509688
units: 230126
value: 0.0
type: LocalParameter

509923
units: 230126
value: 2.16E-11
type: LocalParameter

509942
units: 230126
value: 2.0E-11
type: LocalParameter

966670
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

966470
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.5
initial amount: NaN
in compartment: 963861
type: Species

239351
local parameters: 510117
local parameters: 510116
notes: k1*cAMP*AC_slash_cAMP_minus_PDE_star_-k2*AC_slash_cAMP_minus_PDE_star__slash_PDE_star__slash_PDE_star__cplx
type: KineticLaw

509776
units: 230126
value: 1.0E-11
type: LocalParameter

232128
stoichiometry: 1.0
species: 965490
type: SpeciesReference

964221
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

509921
units: 230126
value: 4.0E-12
type: LocalParameter

235928
stoichiometry: 1.0
species: 964900
type: SpeciesReference

509818
units: 230126
value: 1.0E-12
type: LocalParameter

509982
units: 230211
value: 1.98E-12
type: LocalParameter

509860
units: 230211
value: 1.8E-11
type: LocalParameter

232713
stoichiometry: 1.0
species: 967190
type: SpeciesReference

965140
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

509736
units: 230126
value: 1.0E-12
type: LocalParameter

238285
local parameters: 510066
notes: k3*PP1_minus_active_slash_Deph_minus_thr286c_slash_Deph_minus_thr286c_cplx
type: KineticLaw

965950
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

234176
stoichiometry: 1.0
species: 967210
type: SpeciesReference

238417
stoichiometry: 1.0
species: 966130
type: SpeciesReference

231596
stoichiometry: 1.0
species: 964600
type: SpeciesReference

236930
stoichiometry: 1.0
species: 965275
type: SpeciesReference

509888
units: 230126
value: 1.0E-12
type: LocalParameter

509962
units: 230126
value: 6.0E-13
type: LocalParameter

969490
kinetic law: 235276
product: 235264
reactant: 235251
reactant: 235238
notes: 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.
fast: false
reversible: true
type: Reaction

509922
units: 230211
value: 1.35E-12
type: LocalParameter

235796
local parameters: 509968
local parameters: 509967
notes: k1*MAPK_slash_MAPKK_minus_ser*MAPK_slash_Raf_minus_GTP_minus_Ras_star_-k2*MAPK_slash_Raf_minus_GTP_minus_Ras_star__slash_Raf_minus_GTP_minus_Ras_star__dot_2_slash_Raf_minus_GTP_minus_Ras_star__dot_2_cplx
type: KineticLaw

232152
local parameters: 509748
local parameters: 509746
notes: kf*EGFR_slash_SHC_star_-kb*EGFR_slash_SHC
type: KineticLaw

237389
local parameters: 510031
notes: k3*EGFR_slash_L_dot_EGFR_slash_phosph_Shc_slash_phosph_Shc_cplx
type: KineticLaw

231644
stoichiometry: 1.0
species: 964541
type: SpeciesReference

235466
stoichiometry: 1.0
species: 964700
type: SpeciesReference

964620
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

509941
units: 230126
value: 8.0E-11
type: LocalParameter

236735
stoichiometry: 1.0
species: 965263
type: SpeciesReference

238940
stoichiometry: 1.0
species: 966190
type: SpeciesReference

233562
stoichiometry: 1.0
species: 965330
type: SpeciesReference

234200
local parameters: 509914
local parameters: 509913
notes: k1*CaM_slash_neurogranin*PKC_minus_active-k2*PKC_minus_active_slash_PKC_minus_phosph_minus_neurogranin_slash_PKC_minus_phosph_minus_neurogranin_cplx
type: KineticLaw

235427
stoichiometry: 1.0
species: 964461
type: SpeciesReference

509945
units: 230126
value: 1.0E-11
type: LocalParameter

234646
local parameters: 509927
notes: k3*PLA2_slash_PIP2_minus_PLA2_star__slash_kenz_slash_kenz_cplx
type: KineticLaw

233417
stoichiometry: 1.0
species: 966550
type: SpeciesReference

509983
units: 230126
value: 2.5E-11
type: LocalParameter

510105
units: 230090
value: 20.0
type: LocalParameter

970770
kinetic law: 238429
product: 238417
reactant: 238405
reactant: 238393
notes: From Seki et al ABB 316(2):673-679
fast: false
reversible: true
type: Reaction

509963
units: 230126
value: 1.5E-13
type: LocalParameter

509903
units: 230211
value: 6.0E-12
type: LocalParameter

231184
stoichiometry: 1.0
species: 964501
type: SpeciesReference

230150
exponent: -1.0
scale: 0
multipler: 1.0
kind: SECOND
type: SBMLUnit

509686
units: 230211
value: 6.0E-12
type: LocalParameter

230344
stoichiometry: 1.0
species: 963901
type: SpeciesReference

236796
stoichiometry: 1.0
species: 965263
type: SpeciesReference

509925
units: 230211
value: 2.76E-12
type: LocalParameter

232250
stoichiometry: 1.0
species: 965590
type: SpeciesReference

230857
local parameters: 509632
local parameters: 509630
notes: kf*temp_minus_PIP2*PLA2_slash_PLA2_minus_Ca_star_-kb*PLA2_slash_PIP2_minus_Ca_minus_PLA2_star_
type: KineticLaw

234080
stoichiometry: 1.0
species: 967210
type: SpeciesReference

509944
units: 230126
value: 4.0E-11
type: LocalParameter

964421
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

509778
units: 230126
value: 5.0E-14
type: LocalParameter

235105
stoichiometry: 1.0
species: 964701
type: SpeciesReference

236894
stoichiometry: 1.0
species: 965275
type: SpeciesReference

509738
units: 230126
value: 1.0E-12
type: LocalParameter

233477
stoichiometry: 1.0
species: 965275
type: SpeciesReference

509984
units: 230126
value: 6.0E-12
type: LocalParameter

509862
units: 230126
value: 6.0E-11
type: LocalParameter

235177
local parameters: 509947
local parameters: 509946
notes: k1*Sos_slash_Sos*MAPK_star_-k2*MAPK_star__slash_phosph_Sos_slash_phosph_Sos_cplx
type: KineticLaw

236096
stoichiometry: 1.0
species: 964980
type: SpeciesReference

238855
stoichiometry: 1.0
species: 966270
type: SpeciesReference

509964
units: 230211
value: 3.3E-12
type: LocalParameter

235612
stoichiometry: 1.0
species: 964800
type: SpeciesReference

231558
stoichiometry: 1.0
species: 964620
type: SpeciesReference

509902
units: 230126
value: 4.0E-12
type: LocalParameter

509943
units: 230211
value: 1.95E-12
type: LocalParameter

236144
stoichiometry: 1.0
species: 964740
type: SpeciesReference

509924
units: 230126
value: 5.4E-12
type: LocalParameter

230138
exponent: 1.0
scale: 0
multipler: 1.0
kind: LITRE
type: SBMLUnit

233369
stoichiometry: 1.0
species: 966650
type: SpeciesReference

231571
local parameters: 509696
local parameters: 509694
notes: kf*Gq_slash_G_minus_GDP*Gq_slash_Rec_minus_Glu-kb*Gq_slash_Rec_minus_Glu_minus_Gq
type: KineticLaw

968370
kinetic law: 232555
product: 232543
reactant: 232531
reactant: 232518
notes: 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&S AnnRev Biochem 92 give tau for dissoc as 0.2 sec at low Ca, 0.4 at high. Low Ca = 100 nM = physiol.
fast: false
reversible: true
type: Reaction

968570
kinetic law: 233064
product: 233052
reactant: 233040
reactant: 233028
notes: going on the experience with CaM, we put the fast (high affinity) sites first. We only know (Stemmer and Klee) that the affinity is < 70 nM. Assuming 10 nM at first, we get kf = 2.78e-8, kb = 1. Try 20 nM. kf = 7e-9, kb = 1
fast: false
reversible: true
type: Reaction

235748
local parameters: 509966
notes: k3*MAPK_slash_Raf_minus_GTP_minus_Ras_star__slash_Raf_minus_GTP_minus_Ras_star__dot_1_slash_Raf_minus_GTP_minus_Ras_star__dot_1_cplx
type: KineticLaw

510103
units: 230126
value: 1.8E-11
type: LocalParameter

237002
local parameters: 510015
notes: k3*PKA_minus_active_slash_PKA_minus_phosph_minus_I1_slash_PKA_minus_phosph_minus_I1_cplx
type: KineticLaw

239400
local parameters: 510118
notes: k3*AC_slash_cAMP_minus_PDE_star__slash_PDE_star__slash_PDE_star__cplx
type: KineticLaw

509985
units: 230211
value: 1.98E-12
type: LocalParameter

235300
stoichiometry: 1.0
species: 964121
type: SpeciesReference

232689
local parameters: 509796
local parameters: 509794
notes: kf*CaM_slash_CaM*Ca^2-kb*CaM_minus_TR2_minus_Ca2
type: KineticLaw

509947
units: 230126
value: 4.0E-11
type: LocalParameter

232773
stoichiometry: 1.0
species: 965330
type: SpeciesReference

509664
units: 230126
value: 1.0E-12
type: LocalParameter

235288
stoichiometry: 1.0
species: 964500
type: SpeciesReference

509684
units: 230211
value: 0.0
type: LocalParameter

238176
stoichiometry: 1.0
species: 965910
type: SpeciesReference

238904
stoichiometry: 1.0
species: 966350
type: SpeciesReference

510069
units: 230126
value: 1.4E-12
type: LocalParameter

238333
local parameters: 510069
local parameters: 510067
notes: k1*CaMKII_slash_CaMKII_minus_thr286*PP1_minus_active-k2*PP1_minus_active_slash_Deph_thr286b_slash_Deph_thr286b_cplx
type: KineticLaw

970130
kinetic law: 236857
product: 236845
reactant: 236832
reactant: 236820
notes: 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
fast: false
reversible: true
type: Reaction

235401
stoichiometry: 1.0
species: 964520
type: SpeciesReference

509864
units: 230211
value: 1.8E-11
type: LocalParameter

234152
local parameters: 509912
notes: k3*PKC_minus_active_slash_PKC_minus_act_minus_GEF_slash_PKC_minus_act_minus_GEF_cplx
type: KineticLaw

509986
units: 230126
value: 2.5E-11
type: LocalParameter

510018
units: 230126
value: 3.6E-11
type: LocalParameter

231486
local parameters: 509688
local parameters: 509686
notes: kf*G_star_GDP*BetaGamma-kb*Gq_slash_G_minus_GDP
type: KineticLaw

509946
units: 230211
value: 1.95E-11
type: LocalParameter

968010
kinetic law: 231778
product: 231766
reactant: 231754
reactant: 231742
notes: The rate consts give a total binding affinity of only
fast: false
reversible: true
type: Reaction

232176
stoichiometry: 1.0
species: 965510
type: SpeciesReference

236759
local parameters: 510003
local parameters: 510001
notes: k1*Ras_slash_GDP_minus_Ras*Ras_slash_CaM_minus_GEF-k2*Ras_slash_CaM_minus_GEF_slash_CaM_minus_GEF_minus_act_minus_ras_slash_CaM_minus_GEF_minus_act_minus_ras_cplx
type: KineticLaw

233610
stoichiometry: 1.0
species: 966710
type: SpeciesReference

231620
local parameters: 509700
local parameters: 509698
notes: kf*Glu*Gq_slash_Rec_minus_Gq-kb*Gq_slash_Rec_minus_Glu_minus_Gq
type: KineticLaw

237365
stoichiometry: 1.0
species: 965490
type: SpeciesReference

965350
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

965330
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

509708
units: 230126
value: 1.0E-12
type: LocalParameter

509908
units: 230211
value: 6.0E-12
type: LocalParameter

238261
stoichiometry: 1.0
species: 965810
type: SpeciesReference

967390
kinetic law: 230368
product: 230356
reactant: 230344
reactant: 230332
notes: 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
fast: false
reversible: true
type: Reaction

236000
stoichiometry: 1.0
species: 964940
type: SpeciesReference

968030
kinetic law: 231826
product: 231814
reactant: 231802
reactant: 231790
notes: 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....
fast: false
reversible: true
type: Reaction

509884
units: 230126
value: 1.0E-12
type: LocalParameter

233816
local parameters: 509892
local parameters: 509890
notes: kf*AC_slash_cAMP_minus_PDE_star_-kb*AC_slash_cAMP_minus_PDE
type: KineticLaw

971210
kinetic law: 239498
product: 239485
product: 239472
reactant: 239460
fast: false
reversible: false
type: Reaction

510101
units: 230090
value: 20.0
type: LocalParameter

509987
units: 230126
value: 6.0E-12
type: LocalParameter

238685
stoichiometry: 1.0
species: 966210
type: SpeciesReference

230893
stoichiometry: 1.0
species: 964361
type: SpeciesReference

235515
stoichiometry: 1.0
species: 964780
type: SpeciesReference

234706
stoichiometry: 1.0
species: 964360
type: SpeciesReference

964641
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.2
initial amount: NaN
in compartment: 963861
type: Species

509920
units: 230126
value: 1.6E-11
type: LocalParameter

509662
units: 230211
value: 2.52E-11
type: LocalParameter

230452
stoichiometry: 1.0
species: 963901
type: SpeciesReference

968430
kinetic law: 232689
product: 232677
reactant: 232665
reactant: 232653
notes: 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 & Klee: K1=.9, K2=1.1. Assume 1.0uM for both. kb/kf=3.6e11. If kb=72, kf = 2e-10 (Exactly the same !)....
fast: false
reversible: true
type: Reaction

509949
units: 230211
value: 2.52E-12
type: LocalParameter

230174
exponent: 3.0
scale: 0
multipler: 1.0
kind: LITRE
type: SBMLUnit

230368
local parameters: 509593
local parameters: 509592
notes: kf*DAG*PKC_slash_PKC_minus_Ca-kb*PKC_slash_PKC_minus_Ca_minus_DAG
type: KineticLaw

237184
stoichiometry: 1.0
species: 965350
type: SpeciesReference

970830
kinetic law: 238577
product: 238565
product: 238552
reactant: 238539
fast: false
reversible: false
type: Reaction

237766
stoichiometry: 1.0
species: 965870
type: SpeciesReference

234224
stoichiometry: 1.0
species: 966050
type: SpeciesReference

509907
units: 230126
value: 4.0E-12
type: LocalParameter

965670
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

509868
units: 230126
value: 1.0E-12
type: LocalParameter

234984
local parameters: 509941
local parameters: 509940
notes: k1*PLA2_slash_PLA2_minus_cytosolic*MAPK_star_-k2*MAPK_star__slash_MAPK_star__slash_MAPK_star__cplx
type: KineticLaw

509682
units: 230126
value: 1.0E-16
type: LocalParameter

509988
units: 230211
value: 1.98E-12
type: LocalParameter

964340
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

231534
stoichiometry: 1.0
species: 964561
type: SpeciesReference

236687
stoichiometry: 1.0
species: 965180
type: SpeciesReference

238710
stoichiometry: 1.0
species: 966290
type: SpeciesReference

509866
units: 230211
value: 6.0E-11
type: LocalParameter

509948
units: 230126
value: 1.0E-11
type: LocalParameter

966710
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

230114
exponent: 1.0
scale: -6
multipler: 1.0
kind: MOLE
type: SBMLUnit

238698
stoichiometry: 1.0
species: 966270
type: SpeciesReference

236771
stoichiometry: 1.0
species: 965272
type: SpeciesReference

510016
units: 230211
value: 6.0E-12
type: LocalParameter

235440
stoichiometry: 1.0
species: 964501
type: SpeciesReference

964001
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

232274
stoichiometry: 1.0
species: 965530
type: SpeciesReference

236409
stoichiometry: 1.0
species: 964960
type: SpeciesReference

964380
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

230808
local parameters: 509628
local parameters: 509626
notes: kf*temp_minus_PIP2*PLA2_slash_PLA2_minus_cytosolic-kb*PLA2_slash_PIP2_minus_PLA2_star_
type: KineticLaw

964021
constant: false
boundary condition: false
has only substance units: false
initial concentration: 1.81333333333333E-17
initial amount: NaN
in compartment: 963861
type: Species

232068
local parameters: 509740
local parameters: 509738
notes: kf*Ras_slash_inact_minus_GEF_star_-kb*Ras_slash_inact_minus_GEF
type: KineticLaw

236072
stoichiometry: 1.0
species: 964980
type: SpeciesReference

233453
local parameters: 509860
local parameters: 509858
notes: kf*PKA_slash_R2C2_minus_cAMP4-kb*PKA_minus_active*PKA_slash_R2C_minus_cAMP4
type: KineticLaw

235129
local parameters: 509945
notes: k3*MAPK_star__slash_MAPK_star__minus_feedback_slash_MAPK_star__minus_feedback_cplx
type: KineticLaw

236870
stoichiometry: 1.0
species: 965290
type: SpeciesReference

238831
stoichiometry: 1.0
species: 966310
type: SpeciesReference

509886
units: 230211
value: 8.3328E-10
type: LocalParameter

509989
units: 230126
value: 2.5E-11
type: LocalParameter

234755
stoichiometry: 1.0
species: 967010
type: SpeciesReference

509960
units: 230126
value: 1.5E-13
type: LocalParameter

231778
local parameters: 509712
local parameters: 509710
notes: kf*Gq_slash_Rec_minus_Gq*Gq_slash_mGluRAntag-kb*Gq_slash_Blocked_minus_rec_minus_Gq
type: KineticLaw

509892
units: 230126
value: 0.0
type: LocalParameter

238068
stoichiometry: 1.0
species: 965790
type: SpeciesReference

236966
stoichiometry: 1.0
species: 965291
type: SpeciesReference

231389
local parameters: 509680
local parameters: 509678
notes: kf*Gq_slash_mGluR*Glu-kb*Gq_slash_Rec_minus_Glu
type: KineticLaw

232140
stoichiometry: 1.0
species: 965470
type: SpeciesReference

964700
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.36
initial amount: NaN
in compartment: 963861
type: Species

509658
units: 230126
value: 1.5E-13
type: LocalParameter

236579
stoichiometry: 1.0
species: 965140
type: SpeciesReference

509704
units: 230162
value: 0.0
type: LocalParameter

966790
constant: false
boundary condition: false
has only substance units: false
initial concentration: 325490.0
initial amount: NaN
in compartment: 963881
type: Species

964241
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

510046
units: 230126
value: 2.0E-12
type: LocalParameter

509594
units: 230126
value: 1.2705E-12
type: LocalParameter

233912
local parameters: 509900
local parameters: 509898
notes: k1*MAPK_slash_craf_minus_1*PKC_minus_active-k2*PKC_minus_active_slash_PKC_minus_act_minus_raf_slash_PKC_minus_act_minus_raf_cplx
type: KineticLaw

968810
kinetic law: 233634
product: 233622
reactant: 233610
notes: Random rate.
fast: false
reversible: true
type: Reaction

509724
units: 230126
value: 0.0
type: LocalParameter

966390
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

970290
kinetic law: 237244
product: 237232
reactant: 237220
reactant: 237208
notes: 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.
fast: false
reversible: true
type: Reaction

510026
units: 230211
value: 3.0E-12
type: LocalParameter

509994
units: 230211
value: 1.98E-13
type: LocalParameter

235490
stoichiometry: 1.0
species: 964780
type: SpeciesReference

237996
local parameters: 510050
notes: k3*PP1_minus_active_slash_Deph_minus_thr286_slash_Deph_minus_thr286_cplx
type: KineticLaw

234393
stoichiometry: 1.0
species: 964261
type: SpeciesReference

238770
local parameters: 510083
notes: k3*PP2A_slash_PP2A_minus_dephosph_minus_I1_slash_PP2A_minus_dephosph_minus_I1_cplx
type: KineticLaw

509780
units: 230126
value: 0.0
type: LocalParameter

970250
kinetic law: 237148
product: 237136
reactant: 237124
reactant: 237112
fast: false
reversible: true
type: Reaction

231037
stoichiometry: 1.0
species: 967190
type: SpeciesReference

232579
stoichiometry: 1.0
species: 965330
type: SpeciesReference

232870
local parameters: 509812
local parameters: 509810
notes: kf*CaM_slash_neurogranin_star_-kb*CaM_slash_neurogranin
type: KineticLaw

970990
kinetic law: 238964
product: 238952
product: 238940
reactant: 238928
fast: false
reversible: false
type: Reaction

238381
local parameters: 510071
notes: k3*PP1_minus_active_slash_Deph_thr286b_slash_Deph_thr286b_cplx
type: KineticLaw

970190
kinetic law: 237002
product: 236990
product: 236978
reactant: 236966
fast: false
reversible: false
type: Reaction

964701
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

237112
stoichiometry: 1.0
species: 965180
type: SpeciesReference

967250
constant: false
boundary condition: true
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

234248
local parameters: 509915
notes: k3*PKC_minus_active_slash_PKC_minus_phosph_minus_neurogranin_slash_PKC_minus_phosph_minus_neurogranin_cplx
type: KineticLaw

239558
stoichiometry: 1.0
species: 966970
type: SpeciesReference

510047
units: 230126
value: 5.0E-13
type: LocalParameter

509593
units: 230126
value: 8.6348E-12
type: LocalParameter

231438
local parameters: 509684
local parameters: 509682
notes: kf*Gq_slash_G_minus_GDP-kb*G_star_GTP*BetaGamma
type: KineticLaw

233996
stoichiometry: 1.0
species: 964181
type: SpeciesReference

510027
units: 230126
value: 8.0E-13
type: LocalParameter

509656
units: 230126
value: 0.0
type: LocalParameter

509993
units: 230126
value: 2.0E-14
type: LocalParameter

510111
units: 230211
value: 2.52E-12
type: LocalParameter

964341
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

233052
stoichiometry: 1.0
species: 966390
type: SpeciesReference

970270
kinetic law: 237196
product: 237184
product: 237172
reactant: 237160
fast: false
reversible: false
type: Reaction

964281
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.4
initial amount: NaN
in compartment: 963861
type: Species

230198
exponent: -1.0
scale: 0
multipler: 1.0
kind: SECOND
type: SBMLUnit

967270
constant: false
boundary condition: true
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

509618
units: 230211
value: 1.8E-14
type: LocalParameter

237340
local parameters: 510030
local parameters: 510029
notes: k1*EGFR_slash_SHC*EGFR_slash_L_dot_EGFR-k2*EGFR_slash_L_dot_EGFR_slash_phosph_Shc_slash_phosph_Shc_cplx
type: KineticLaw

230283
stoichiometry: 1.0
species: 964101
type: SpeciesReference

238637
stoichiometry: 1.0
species: 966170
type: SpeciesReference

509894
units: 230211
value: 7.2E-10
type: LocalParameter

231413
stoichiometry: 1.0
species: 964541
type: SpeciesReference

235844
local parameters: 509969
notes: k3*MAPK_slash_Raf_minus_GTP_minus_Ras_star__slash_Raf_minus_GTP_minus_Ras_star__dot_2_slash_Raf_minus_GTP_minus_Ras_star__dot_2_cplx
type: KineticLaw

509596
units: 230126
value: 1.0E-12
type: LocalParameter

509706
units: 230211
value: 6.0E-13
type: LocalParameter

509830
units: 230211
value: 2.4E-13
type: LocalParameter

510044
units: 230126
value: 6.0E-12
type: LocalParameter

236024
stoichiometry: 1.0
species: 964900
type: SpeciesReference

238734
stoichiometry: 1.0
species: 966290
type: SpeciesReference

509850
units: 230211
value: 7.5E-11
type: LocalParameter

232907
stoichiometry: 1.0
species: 966230
type: SpeciesReference

509782
units: 230211
value: 4.99998E-11
type: LocalParameter

509726
units: 230126
value: 1.0E-16
type: LocalParameter

509996
units: 230126
value: 2.0E-14
type: LocalParameter

239037
stoichiometry: 1.0
species: 966650
type: SpeciesReference

233489
stoichiometry: 1.0
species: 966590
type: SpeciesReference

239122
stoichiometry: 1.0
species: 967170
type: SpeciesReference

233695
stoichiometry: 1.0
species: 966990
type: SpeciesReference

968190
kinetic law: 232152
product: 232140
reactant: 232128
notes: 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.
fast: false
reversible: true
type: Reaction

234513
stoichiometry: 1.0
species: 964320
type: SpeciesReference

509812
units: 230126
value: 0.0
type: LocalParameter

238928
stoichiometry: 1.0
species: 966350
type: SpeciesReference

230844
stoichiometry: 1.0
species: 964341
type: SpeciesReference

509810
units: 230126
value: 5.0E-15
type: LocalParameter

233888
stoichiometry: 1.0
species: 967210
type: SpeciesReference

509595
units: 230126
value: 3.5026E-12
type: LocalParameter

237076
stoichiometry: 1.0
species: 966870
type: SpeciesReference

235625
stoichiometry: 1.0
species: 964421
type: SpeciesReference

510045
units: 230211
value: 1.4286E-14
type: LocalParameter

230551
stoichiometry: 1.0
species: 964001
type: SpeciesReference

230638
stoichiometry: 1.0
species: 964121
type: SpeciesReference

235238
stoichiometry: 1.0
species: 967110
type: SpeciesReference

509654
units: 230126
value: 2.5E-12
type: LocalParameter

510025
units: 230126
value: 2.0E-14
type: LocalParameter

237669
stoichiometry: 1.0
species: 965850
type: SpeciesReference

509995
units: 230126
value: 8.0E-14
type: LocalParameter

235044
stoichiometry: 1.0
species: 964660
type: SpeciesReference

235324
stoichiometry: 1.0
species: 964481
type: SpeciesReference

234791
local parameters: 509934
local parameters: 509932
notes: k1*PLA2_slash_APC*PLA2_slash_DAG_minus_Ca_minus_PLA2_star_-k2*PLA2_slash_DAG_minus_Ca_minus_PLA2_star__slash_kenz_slash_kenz_cplx
type: KineticLaw

238080
stoichiometry: 1.0
species: 965910
type: SpeciesReference

237935
stoichiometry: 1.0
species: 964760
type: SpeciesReference

509616
units: 230126
value: 1.0E-13
type: LocalParameter

234935
local parameters: 509939
notes: k3*PLA2_slash_PLA2_star__minus_Ca_slash_kenz_slash_kenz_cplx
type: KineticLaw

509590
units: 230211
value: 6.0E-13
type: LocalParameter

231013
stoichiometry: 1.0
species: 964281
type: SpeciesReference

233719
stoichiometry: 1.0
species: 966770
type: SpeciesReference

509926
units: 230126
value: 4.416E-11
type: LocalParameter

509999
units: 230126
value: 1.0E-11
type: LocalParameter

232481
stoichiometry: 1.0
species: 965690
type: SpeciesReference

967470
kinetic law: 230526
product: 230513
reactant: 230501
notes: Assume slowish too. Schaechter and Benowitz
fast: false
reversible: true
type: Reaction

236168
stoichiometry: 1.0
species: 965000
type: SpeciesReference

237972
stoichiometry: 1.0
species: 965730
type: SpeciesReference

235362
stoichiometry: 1.0
species: 964501
type: SpeciesReference

235349
stoichiometry: 1.0
species: 967110
type: SpeciesReference

509900
units: 230126
value: 1.6E-11
type: LocalParameter

509814
units: 230211
value: 4.9998E-10
type: LocalParameter

238795
stoichiometry: 1.0
species: 966270
type: SpeciesReference

231754
stoichiometry: 1.0
species: 967130
type: SpeciesReference

509998
units: 230126
value: 4.0E-11
type: LocalParameter

234284
stoichiometry: 1.0
species: 964241
type: SpeciesReference

509990
units: 230126
value: 6.0E-12
type: LocalParameter

509784
units: 230126
value: 5.0E-12
type: LocalParameter

236555
stoichiometry: 1.0
species: 965140
type: SpeciesReference

509728
units: 230126
value: 0.0
type: LocalParameter

231365
stoichiometry: 1.0
species: 967050
type: SpeciesReference

968890
kinetic law: 233816
product: 233803
reactant: 233791
notes: 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.
fast: false
reversible: true
type: Reaction

509852
units: 230126
value: 1.1E-10
type: LocalParameter

509927
units: 230126
value: 1.104E-11
type: LocalParameter

237887
stoichiometry: 1.0
species: 967250
type: SpeciesReference

969390
kinetic law: 235032
product: 235020
product: 235008
reactant: 234996
fast: false
reversible: false
type: Reaction

969530
kinetic law: 235388
product: 235375
reactant: 235362
reactant: 235349
notes: 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
fast: false
reversible: true
type: Reaction

233076
stoichiometry: 1.0
species: 966330
type: SpeciesReference

968850
kinetic law: 233731
product: 233719
reactant: 233707
reactant: 233695
notes: Half-max 8nM from Tang et al JBC266:13 8595-8603 kb/kf = 8 nM = 4800#/cell so kf = kb * 2.08e-4
fast: false
reversible: true
type: Reaction

238044
local parameters: 510054
local parameters: 510052
notes: k1*CaMKII_slash_CaMKII_star__star__star_*PP1_minus_active-k2*PP1_minus_active_slash_Deph_minus_thr305_slash_Deph_minus_thr305_cplx
type: KineticLaw

233972
stoichiometry: 1.0
species: 965220
type: SpeciesReference

967910
kinetic law: 231522
product: 231510
reactant: 231498
notes: From Berstein et al JBC 267:12 8081-8088 1992, kcat for GTPase activity of Gq is only 0.8/min
fast: false
reversible: true
type: Reaction

232555
local parameters: 509784
local parameters: 509782
notes: kf*CaM_minus_Ca4*CaMKII_slash_CaMKII-kb*CaMKII_slash_CaMKII_minus_CaM
type: KineticLaw

232894
stoichiometry: 1.0
species: 965910
type: SpeciesReference

235976
stoichiometry: 1.0
species: 964940
type: SpeciesReference

968870
kinetic law: 233779
product: 233767
reactant: 233755
reactant: 233743
notes: kb/kf = 1.2 nM so kf = kb/720 = 1.3888 * kb.
fast: false
reversible: true
type: Reaction

969510
kinetic law: 235336
product: 235324
product: 235312
product: 235300
reactant: 235288
fast: false
reversible: false
type: Reaction

510023
units: 230126
value: 8.0E-14
type: LocalParameter

237136
stoichiometry: 1.0
species: 965370
type: SpeciesReference

509997
units: 230211
value: 4.94856E-11
type: LocalParameter

509700
units: 230126
value: 1.0E-13
type: LocalParameter

965610
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.1
initial amount: NaN
in compartment: 963861
type: Species

239534
stoichiometry: 1.0
species: 966970
type: SpeciesReference

231692
stoichiometry: 1.0
species: 964561
type: SpeciesReference

510048
units: 230211
value: 3.432E-13
type: LocalParameter

509890
units: 230126
value: 1.0E-13
type: LocalParameter

509592
units: 230211
value: 7.9998E-15
type: LocalParameter

965550
constant: false
boundary condition: false
has only substance units: false
initial concentration: 1.0
initial amount: NaN
in compartment: 963861
type: Species

235008
stoichiometry: 1.0
species: 964420
type: SpeciesReference

509928
units: 230211
value: 9.0E-12
type: LocalParameter

509702
units: 230126
value: 1.0E-14
type: LocalParameter

967890
kinetic law: 231486
product: 231474
reactant: 231462
reactant: 231450
notes: kf == kg3 = 1e-5 /cell/sec. As usual, there is no back-reaction kb = 0
fast: false
reversible: true
type: Reaction

970630
kinetic law: 238092
product: 238080
product: 238068
reactant: 238056
fast: false
reversible: false
type: Reaction

968250
kinetic law: 232286
product: 232274
reactant: 232262
reactant: 232250
notes: 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.
fast: false
reversible: true
type: Reaction

967570
kinetic law: 230759
product: 230747
reactant: 230735
reactant: 230723
notes: Leslie and Channon BBA 1045 (1990) 261-270 fig6 pp267.
fast: false
reversible: true
type: Reaction

232286
local parameters: 509760
local parameters: 509758
notes: kf*Sos_slash_Sos_star_*Sos_slash_Grb2-kb*Sos_slash_Sos_star__dot_Grb2
type: KineticLaw

235904
stoichiometry: 1.0
species: 964920
type: SpeciesReference

233671
stoichiometry: 1.0
species: 966730
type: SpeciesReference

964320
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

234537
stoichiometry: 1.0
species: 964301
type: SpeciesReference

238758
stoichiometry: 1.0
species: 966270
type: SpeciesReference

230576
stoichiometry: 1.0
species: 964141
type: SpeciesReference

967550
kinetic law: 230710
product: 230698
reactant: 230686
reactant: 230674
notes: 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.
fast: false
reversible: true
type: Reaction

970650
kinetic law: 238140
product: 238128
reactant: 238116
reactant: 238104
notes: See Cohen et al
fast: false
reversible: true
type: Reaction

509992
units: 230126
value: 8.0E-14
type: LocalParameter

509816
units: 230126
value: 1.0E-13
type: LocalParameter

964321
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

235868
stoichiometry: 1.0
species: 964900
type: SpeciesReference

966830
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.45
initial amount: NaN
in compartment: 963861
type: Species

233332
stoichiometry: 1.0
species: 966650
type: SpeciesReference

239012
local parameters: 510093
local parameters: 510091
notes: kcat*AC_slash_AC1_minus_CaM*AC_slash_ATP/(Km+AC_slash_ATP)
type: KineticLaw

230235
exponent: -1.0
scale: -6
multipler: 1.0
kind: MOLE
type: SBMLUnit

509870
units: 230211
value: 4.99998E-11
type: LocalParameter

967870
kinetic law: 231438
product: 231426
product: 231413
reactant: 231401
notes: kf = kg1 = 0.01/sec, kb = 0. This is the basal exchange of GTP for GDP.
fast: false
reversible: true
type: Reaction

235388
local parameters: 509953
local parameters: 509952
notes: k1*PIP2*PLCbeta_slash_PLC_minus_Ca_minus_Gq-k2*PLCbeta_slash_PLC_minus_Ca_minus_Gq_slash_PLCb_minus_Ca_minus_Gq_slash_PLCb_minus_Ca_minus_Gq_cplx
type: KineticLaw

509854
units: 230211
value: 7.5E-11
type: LocalParameter

509786
units: 230211
value: 1.0002E-9
type: LocalParameter

238613
stoichiometry: 1.0
species: 966170
type: SpeciesReference

236048
stoichiometry: 1.0
species: 964660
type: SpeciesReference

965570
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

968230
kinetic law: 232237
product: 232225
reactant: 232213
reactant: 232201
notes: 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.
fast: false
reversible: true
type: Reaction

238527
local parameters: 510076
local parameters: 510075
notes: k1*PP1_slash_I1_star_*CaM_po_Ca_pc_n_minus_CaNAB-k2*CaM_po_Ca_pc_n_minus_CaNAB_slash_dephosph_inhib1_slash_dephosph_inhib1_cplx
type: KineticLaw

510020
units: 230126
value: 9.0E-12
type: LocalParameter

509591
units: 230126
value: 5.0E-13
type: LocalParameter

509678
units: 230211
value: 1.68E-11
type: LocalParameter

510049
units: 230126
value: 1.4E-12
type: LocalParameter

968270
kinetic law: 232323
product: 232310
reactant: 232298
notes: 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
fast: false
reversible: true
type: Reaction

238104
stoichiometry: 1.0
species: 965810
type: SpeciesReference

509856
units: 230126
value: 3.25E-11
type: LocalParameter

968830
kinetic law: 233683
product: 233671
reactant: 233659
reactant: 233646
notes: 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
fast: false
reversible: true
type: Reaction

235068
stoichiometry: 1.0
species: 964441
type: SpeciesReference

234827
stoichiometry: 1.0
species: 964361
type: SpeciesReference

967510
kinetic law: 230613
product: 230601
reactant: 230588
reactant: 230576
notes: Raise kf from 1.667e-10 to 2e-10 to get better match to data.
fast: false
reversible: true
type: Reaction

509929
units: 230126
value: 1.44E-10
type: LocalParameter

234453
local parameters: 509921
notes: k3*PKC_minus_active_slash_phosph_minus_AC2_slash_phosph_minus_AC2_cplx
type: KineticLaw

234911
stoichiometry: 1.0
species: 964141
type: SpeciesReference

237959
stoichiometry: 1.0
species: 964760
type: SpeciesReference

963846
constant: true
size: 1.0E-18
spatial dimensions: 3.0
type: Compartment

509991
units: 230211
value: 1.98E-13
type: LocalParameter

230820
stoichiometry: 1.0
species: 967030
type: SpeciesReference

230247
exponent: -1.0
scale: 0
multipler: 1.0
kind: SECOND
type: SBMLUnit

965590
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

237052
local parameters: 510018
local parameters: 510016
notes: k1*AC_slash_cAMP_minus_PDE*PKA_minus_active-k2*PKA_minus_active_slash_phosph_minus_PDE_slash_phosph_minus_PDE_cplx
type: KineticLaw

968350
kinetic law: 232505
product: 232493
reactant: 232481
fast: false
reversible: true
type: Reaction

233149
stoichiometry: 1.0
species: 966410
type: SpeciesReference

965650
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

237172
stoichiometry: 1.0
species: 965160
type: SpeciesReference

970010
kinetic law: 236567
product: 236555
reactant: 236543
reactant: 236531
notes: Kinetics same as GEF-bg-act-ras
fast: false
reversible: true
type: Reaction

230392
stoichiometry: 1.0
species: 963961
type: SpeciesReference

967530
kinetic law: 230662
product: 230650
reactant: 230638
reactant: 230626
notes: 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
fast: false
reversible: true
type: Reaction

968290
kinetic law: 232371
product: 232359
reactant: 232347
reactant: 232335
notes: 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.
fast: false
reversible: true
type: Reaction

510021
units: 230211
value: 1.98E-13
type: LocalParameter

236446
stoichiometry: 1.0
species: 965060
type: SpeciesReference

964940
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

237244
local parameters: 510027
local parameters: 510026
notes: k1*PLC_g_slash_Ca_dot_PLC_g*EGFR_slash_L_dot_EGFR-k2*EGFR_slash_L_dot_EGFR_slash_phosph_PLC_g_slash_phosph_PLC_g_cplx
type: KineticLaw

233501
local parameters: 509864
local parameters: 509862
notes: kf*PKA_slash_R2C_minus_cAMP4-kb*PKA_minus_active*PKA_slash_R2_minus_cAMP4
type: KineticLaw

966870
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

236906
local parameters: 510010
notes: k3*PKA_minus_active_slash_PKA_minus_phosph_minus_GEF_slash_PKA_minus_phosph_minus_GEF_cplx
type: KineticLaw

966030
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

232628
stoichiometry: 1.0
species: 965790
type: SpeciesReference

967050
notes: 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.
constant: true
boundary condition: true
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

966630
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

235952
stoichiometry: 1.0
species: 964421
type: SpeciesReference

239510
stoichiometry: 1.0
species: 966650
type: SpeciesReference

232531
stoichiometry: 1.0
species: 965710
type: SpeciesReference

232967
local parameters: 509820
local parameters: 509818
notes: kf*PP1_slash_PP1_minus_I1-kb*PP1_minus_active*PP1_slash_I1
type: KineticLaw

966010
constant: false
boundary condition: false
has only substance units: false
initial concentration: 20.0
initial amount: NaN
in compartment: 963861
type: Species

233271
stoichiometry: 1.0
species: 966490
type: SpeciesReference

231923
stoichiometry: 1.0
species: 965160
type: SpeciesReference

237522
stoichiometry: 1.0
species: 965790
type: SpeciesReference

234260
stoichiometry: 1.0
species: 966030
type: SpeciesReference

232213
stoichiometry: 1.0
species: 965490
type: SpeciesReference

967030
notes: This isn\'t explicitly present in the M&L 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....
constant: true
boundary condition: true
has only substance units: false
initial concentration: 2.5
initial amount: NaN
in compartment: 963861
type: Species

238020
stoichiometry: 1.0
species: 965910
type: SpeciesReference

966850
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

964920
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

967070
constant: true
boundary condition: true
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

509838
units: 230211
value: 6.0E-10
type: LocalParameter

236832
stoichiometry: 1.0
species: 965275
type: SpeciesReference

239327
stoichiometry: 1.0
species: 966870
type: SpeciesReference

509760
units: 230126
value: 1.68E-14
type: LocalParameter

231257
stoichiometry: 1.0
species: 964480
type: SpeciesReference

235251
stoichiometry: 1.0
species: 964481
type: SpeciesReference

236531
stoichiometry: 1.0
species: 965180
type: SpeciesReference

969910
kinetic law: 236324
product: 236312
product: 236300
reactant: 236288
fast: false
reversible: false
type: Reaction

231341
local parameters: 509676
local parameters: 509674
notes: kf*Ca*PLCbeta_slash_PLC_minus_Gq-kb*PLCbeta_slash_PLC_minus_Ca_minus_Gq
type: KineticLaw

234875
stoichiometry: 1.0
species: 964401
type: SpeciesReference

239182
stoichiometry: 1.0
species: 966650
type: SpeciesReference

230613
local parameters: 509612
local parameters: 509610
notes: kf*AA*PKC_slash_PKC_minus_cytosolic-kb*PKC_slash_PKC_minus_AA_star_
type: KineticLaw

237534
stoichiometry: 1.0
species: 967230
type: SpeciesReference

233185
stoichiometry: 1.0
species: 966330
type: SpeciesReference

509638
units: 230126
value: 4.0E-13
type: LocalParameter

966770
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

964261
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

964900
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0024
initial amount: NaN
in compartment: 963861
type: Species

964980
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

237862
stoichiometry: 1.0
species: 965890
type: SpeciesReference

509858
units: 230126
value: 6.0E-11
type: LocalParameter

967090
notes: Phosphatidylcholine is the main (around 55%) metabolic product of DAG, follwed by PE (around 25%). Ref is Welsh and Cabot, JCB35:231-245(1987)
constant: true
boundary condition: true
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963881
type: Species

231983
local parameters: 509732
local parameters: 509730
notes: kf*Ras_slash_GAP_star_-kb*Ras_slash_GAP
type: KineticLaw

970730
kinetic law: 238333
product: 238321
reactant: 238309
reactant: 238297
fast: false
reversible: true
type: Reaction

MODEL9081220742
reaction: 971210
species: 964800
reaction: 970610
reaction: 970790
reaction: 969590
species: 966730
species: 966990
species: 965610
reaction: 969070
reaction: 970810
reaction: 969630
reaction: 967570
species: 966470
species: 966570
species: 964680
reaction: 970630
reaction: 971190
reaction: 968210
species: 965690
reaction: 968770
species: 966390
reaction: 968810
reaction: 968130
reaction: 970990
species: 966510
reaction: 969370
species: 964720
species: 964281
reaction: 969410
species: 966350
reaction: 967930
reaction: 969210
species: 964920
reaction: 967370
reaction: 968630
reaction: 970410
notes: This is a network model of many pathways present at the neuronal synapse. The network has properties of temporal tuning as well as steady-state computational properties. In its default form the network is bistable.Bhalla US Biophys J. 2004 Aug;87(2):745-53 This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2011 The BioModels.net Team. To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information. In summary, you are entitled to use this encoded model in absolutely any manner you deem suitable, verbatim, or with modification, alone or embedded it in a larger context, redistribute it, commercially or not, in a restricted way or not.. To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.
reaction: 968150
species: 965411
species: 965730
species: 964521
species: 965470
reaction: 968970
species: 964340
species: 966810
rule: 967330
reaction: 969830
reaction: 969570
reaction: 970770
species: 963961
species: 964500
reaction: 969610
reaction: 968290
reaction: 970390
reaction: 968550
reaction: 970590
species: 966150
reaction: 969490
reaction: 968750
species: 965750
reaction: 969150
species: 964101
reaction: 969350
species: 966750
species: 964641
species: 965120
reaction: 967490
reaction: 967690
species: 966930
reaction: 969170
species: 965670
reaction: 967910
species: 964381
species: 964481
reaction: 971030
species: 965830
species: 966250
species: 965040
species: 964880
reaction: 969990

233840
stoichiometry: 1.0
species: 965330
type: SpeciesReference

509634
units: 230211
value: 3.0E-15
type: LocalParameter

969710
kinetic law: 235844
product: 235832
product: 235820
reactant: 235808
fast: false
reversible: false
type: Reaction

233125
stoichiometry: 1.0
species: 966090
type: SpeciesReference

969690
kinetic law: 235796
product: 235784
reactant: 235772
reactant: 235760
notes: 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
fast: false
reversible: true
type: Reaction

236204
stoichiometry: 1.0
species: 964820
type: SpeciesReference

971070
kinetic law: 239158
modifier: 239146
product: 239134
reactant: 239122
fast: false
reversible: false
type: Reaction

964461
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.73
initial amount: NaN
in compartment: 963861
type: Species

966170
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

235892
local parameters: 509971
local parameters: 509970
notes: k1*MAPK_slash_MAPK_minus_tyr*MKP_minus_1-k2*MKP_minus_1_slash_MKP1_minus_tyr_minus_deph_slash_MKP1_minus_tyr_minus_deph_cplx
type: KineticLaw

235551
local parameters: 509960
notes: k3*MAPK_slash_MAPKK_star__slash_MAPKKtyr_slash_MAPKKtyr_cplx
type: KineticLaw

971050
kinetic law: 239110
modifier: 239098
product: 239085
reactant: 239073
fast: false
reversible: false
type: Reaction

234008
local parameters: 509905
local parameters: 509903
notes: k1*Ras_slash_GAP*PKC_minus_active-k2*PKC_minus_active_slash_PKC_minus_inact_minus_GAP_slash_PKC_minus_inact_minus_GAP_cplx
type: KineticLaw

239255
local parameters: 510113
local parameters: 510111
notes: k1*cAMP*AC_slash_cAMP_minus_PDE-k2*AC_slash_cAMP_minus_PDE_slash_PDE_slash_PDE_cplx
type: KineticLaw

234561
stoichiometry: 1.0
species: 967010
type: SpeciesReference

237474
stoichiometry: 1.0
species: 964121
type: SpeciesReference

234803
stoichiometry: 1.0
species: 964380
type: SpeciesReference

966430
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

966110
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

966150
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

965100
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.1
initial amount: NaN
in compartment: 963861
type: Species

238867
local parameters: 510086
notes: k3*PP2A_slash_PP2A_minus_dephosph_minus_PP1_minus_I_star__slash_PP2A_minus_dephosph_minus_PP1_minus_I_star__cplx
type: KineticLaw

238212
stoichiometry: 1.0
species: 965910
type: SpeciesReference

230929
stoichiometry: 1.0
species: 967010
type: SpeciesReference

234477
stoichiometry: 1.0
species: 964301
type: SpeciesReference

971010
kinetic law: 239012
modifier: 239000
product: 238988
reactant: 238976
fast: false
reversible: false
type: Reaction

230526
local parameters: 509604
local parameters: 509602
notes: kf*PKC_slash_PKC_minus_DAG_minus_AA-kb*PKC_slash_PKC_minus_DAG_minus_AA_star_
type: KineticLaw

238503
stoichiometry: 1.0
species: 967270
type: SpeciesReference

237729
stoichiometry: 1.0
species: 967250
type: SpeciesReference

966190
constant: false
boundary condition: false
has only substance units: false
initial concentration: 1.8
initial amount: NaN
in compartment: 963861
type: Species

232444
stoichiometry: 1.0
species: 965650
type: SpeciesReference

509762
units: 230126
value: 1.0E-15
type: LocalParameter

964460
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

230650
stoichiometry: 1.0
species: 964061
type: SpeciesReference

237802
local parameters: 510044
notes: k3*CaMKII_slash_tot_autonomous_CaMKII_slash_auton_305_slash_auton_305_cplx
type: KineticLaw

509636
units: 230126
value: 4.0E-12
type: LocalParameter

232591
stoichiometry: 1.0
species: 965750
type: SpeciesReference

969790
kinetic law: 236036
product: 236024
product: 236012
reactant: 236000
fast: false
reversible: false
type: Reaction

971030
kinetic law: 239061
modifier: 239049
product: 239037
reactant: 239024
notes: Reduced Km to match expt data for basal activation of AC2 by PKC. Now k1 = 2.9e-6, k2 = 72, k3 = 18
fast: false
reversible: false
type: Reaction

965990
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

237681
stoichiometry: 1.0
species: 965750
type: SpeciesReference

237280
stoichiometry: 1.0
species: 965411
type: SpeciesReference

964061
constant: false
boundary condition: false
has only substance units: false
initial concentration: 1.16101666666667E-16
initial amount: NaN
in compartment: 963861
type: Species

232943
stoichiometry: 1.0
species: 965910
type: SpeciesReference

968670
kinetic law: 233308
product: 233295
reactant: 233283
reactant: 233271
notes: 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
fast: false
reversible: true
type: Reaction

230710
local parameters: 509620
local parameters: 509618
notes: kf*PKC_slash_PKC_minus_DAG*AA-kb*PKC_slash_PKC_minus_DAG_minus_AA
type: KineticLaw

509632
units: 230126
value: 1.0E-13
type: LocalParameter

232604
local parameters: 509788
local parameters: 509786
notes: kf*CaMKII_slash_CaMKII_minus_thr286*CaM_minus_Ca4-kb*CaMKII_slash_CaMKII_minus_thr286_star__minus_CaM
type: KineticLaw

510003
units: 230126
value: 8.0E-14
type: LocalParameter

239291
stoichiometry: 1.0
species: 966830
type: SpeciesReference

233381
stoichiometry: 1.0
species: 966530
type: SpeciesReference

232237
local parameters: 509756
local parameters: 509754
notes: kf*Sos_slash_Sos_dot_Grb2*EGFR_slash_SHC_star_-kb*Shc_star__dot_Sos_dot_Grb2
type: KineticLaw

510041
units: 230126
value: 5.0E-13
type: LocalParameter

237268
stoichiometry: 1.0
species: 965690
type: SpeciesReference

509832
units: 230126
value: 1.0E-12
type: LocalParameter

236857
local parameters: 510008
local parameters: 510006
notes: k1*Ras_slash_inact_minus_GEF*PKA_minus_active-k2*PKA_minus_active_slash_PKA_minus_phosph_minus_GEF_slash_PKA_minus_phosph_minus_GEF_cplx
type: KineticLaw

964041
constant: false
boundary condition: false
has only substance units: false
initial concentration: 8.46316666666667E-23
initial amount: NaN
in compartment: 963861
type: Species

231887
stoichiometry: 1.0
species: 965120
type: SpeciesReference

509598
units: 230211
value: 1.2E-15
type: LocalParameter

231947
local parameters: 509728
local parameters: 509726
notes: kf*Ras_slash_GTP_minus_Ras-kb*Ras_slash_GDP_minus_Ras
type: KineticLaw

509612
units: 230126
value: 1.0E-13
type: LocalParameter

969310
kinetic law: 234839
product: 234827
product: 234815
reactant: 234803
fast: false
reversible: false
type: Reaction

237558
local parameters: 510037
local parameters: 510036
notes: k1*CaMKII_slash_CaMKII_minus_thr286*CaMKII_slash_tot_CaM_CaMKII-k2*CaMKII_slash_tot_CaM_CaMKII_slash_CaM_act_305_slash_CaM_act_305_cplx
type: KineticLaw

509614
units: 230211
value: 6.0E-16
type: LocalParameter

236482
stoichiometry: 1.0
species: 965080
type: SpeciesReference

964680
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.18
initial amount: NaN
in compartment: 963861
type: Species

967930
kinetic law: 231571
product: 231558
reactant: 231546
reactant: 231534
notes: 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 <= 0.0001, so kf = 1e-8 by detailed balance. This reaction appears to be neglible.
fast: false
reversible: true
type: Reaction

509834
units: 230211
value: 2.238E-12
type: LocalParameter

238309
stoichiometry: 1.0
species: 965910
type: SpeciesReference

510042
units: 230211
value: 1.71426E-13
type: LocalParameter

510043
units: 230126
value: 2.4E-11
type: LocalParameter

233526
stoichiometry: 1.0
species: 966610
type: SpeciesReference

236397
stoichiometry: 1.0
species: 964660
type: SpeciesReference

965630
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.82
initial amount: NaN
in compartment: 963861
type: Species

509720
units: 230126
value: 1.0E-12
type: LocalParameter

969110
kinetic law: 234357
product: 234345
product: 234333
product: 234320
reactant: 234308
fast: false
reversible: false
type: Reaction

231233
stoichiometry: 1.0
species: 964481
type: SpeciesReference

232761
stoichiometry: 1.0
species: 967190
type: SpeciesReference

509597
units: 230126
value: 1.0E-13
type: LocalParameter

510080
units: 230126
value: 3.4E-13
type: LocalParameter

965310
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

234899
stoichiometry: 1.0
species: 964401
type: SpeciesReference

964660
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

233936
stoichiometry: 1.0
species: 964660
type: SpeciesReference

239231
stoichiometry: 1.0
species: 966830
type: SpeciesReference

234585
stoichiometry: 1.0
species: 964340
type: SpeciesReference

510001
units: 230211
value: 1.98E-13
type: LocalParameter

509630
units: 230211
value: 1.2E-14
type: LocalParameter

965370
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

239594
local parameters: 510124
notes: k3*AC_slash_CaM_dot_PDE1_slash_CaM_dot_PDE1_slash_CaM_dot_PDE1_cplx
type: KineticLaw

970450
kinetic law: 237657
product: 237644
reactant: 237632
reactant: 237620
fast: false
reversible: true
type: Reaction

230905
local parameters: 509636
local parameters: 509634
notes: kf*DAG*PLA2_slash_PLA2_minus_Ca_star_-kb*PLA2_slash_DAG_minus_Ca_minus_PLA2_star_
type: KineticLaw

237911
stoichiometry: 1.0
species: 965750
type: SpeciesReference

238236
local parameters: 510064
local parameters: 510062
notes: k1*CaMKII_slash_CaMKII_star__star__star_*PP1_minus_active-k2*PP1_minus_active_slash_Deph_minus_thr286c_slash_Deph_minus_thr286c_cplx
type: KineticLaw

234959
stoichiometry: 1.0
species: 964421
type: SpeciesReference

235214
stoichiometry: 1.0
species: 964421
type: SpeciesReference

965390
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.166666666666667
initial amount: NaN
in compartment: 963861
type: Species

231086
stoichiometry: 1.0
species: 964461
type: SpeciesReference

970470
kinetic law: 237705
product: 237693
product: 237681
reactant: 237669
fast: false
reversible: false
type: Reaction

233864
local parameters: 509896
local parameters: 509894
notes: kf*AC_slash_PDE1*CaM_minus_Ca4-kb*AC_slash_CaM_dot_PDE1
type: KineticLaw

509610
units: 230211
value: 1.2E-16
type: LocalParameter

966810
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

510081
units: 230211
value: 3.96E-12
type: LocalParameter

231608
stoichiometry: 1.0
species: 964620
type: SpeciesReference

230102
exponent: -1.0
scale: 0
multipler: 1.0
kind: LITRE
type: SBMLUnit

231147
local parameters: 509660
local parameters: 509658
notes: kf*DAG-kb*PLCbeta_slash_PC
type: KineticLaw

230428
stoichiometry: 1.0
species: 963981
type: SpeciesReference

237826
stoichiometry: 1.0
species: 967250
type: SpeciesReference

970430
kinetic law: 237607
product: 237595
product: 237583
reactant: 237570
fast: false
reversible: false
type: Reaction

234405
local parameters: 509920
local parameters: 509919
notes: k1*AC_slash_AC2*PKC_minus_active-k2*PKC_minus_active_slash_phosph_minus_AC2_slash_phosph_minus_AC2_cplx
type: KineticLaw

235093
stoichiometry: 1.0
species: 964441
type: SpeciesReference

510040
units: 230126
value: 2.0E-12
type: LocalParameter

964301
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

509836
units: 230126
value: 1.0E-12
type: LocalParameter

230501
stoichiometry: 1.0
species: 964081
type: SpeciesReference

232347
stoichiometry: 1.0
species: 965610
type: SpeciesReference

232420
local parameters: 509772
local parameters: 509770
notes: kf*PLC_g_slash_PLC_g*Ca-kb*PLC_g_slash_Ca_dot_PLC_g
type: KineticLaw

509722
units: 230126
value: 1.0E-12
type: LocalParameter

238819
local parameters: 510085
local parameters: 510084
notes: k1*PP1_slash_PP1_minus_I1_star_*PP2A-k2*PP2A_slash_PP2A_minus_dephosph_minus_PP1_minus_I_star__slash_PP2A_minus_dephosph_minus_PP1_minus_I_star__cplx
type: KineticLaw

237450
local parameters: 510033
local parameters: 510032
notes: kcat*PLC_g_slash_Ca_dot_PLC_g*PIP2/(Km+PIP2)
type: KineticLaw

235820
stoichiometry: 1.0
species: 964740
type: SpeciesReference

233295
stoichiometry: 1.0
species: 966510
type: SpeciesReference

235020
stoichiometry: 1.0
species: 964421
type: SpeciesReference

231293
local parameters: 509672
local parameters: 509670
notes: kf*PLCbeta_slash_PLC*G_star_GTP-kb*PLCbeta_slash_PLC_minus_Gq
type: KineticLaw

233016
local parameters: 509824
local parameters: 509822
notes: kf*Ca^2*PP2B_slash_CaNAB_minus_Ca2-kb*CaNAB_minus_Ca4
type: KineticLaw

510082
units: 230126
value: 2.5E-11
type: LocalParameter

970410
kinetic law: 237558
product: 237546
reactant: 237534
reactant: 237522
notes: Rates from autocamtide phosphorylation, from Hanson and Schulman JBC 267:24 17216-17224 1992. Jan 1 1998: Speed up 12x to match fig 5.
fast: false
reversible: true
type: Reaction

232056
stoichiometry: 1.0
species: 965100
type: SpeciesReference

236060
stoichiometry: 1.0
species: 964960
type: SpeciesReference

231850
stoichiometry: 1.0
species: 965100
type: SpeciesReference

234682
stoichiometry: 1.0
species: 964360
type: SpeciesReference

234345
stoichiometry: 1.0
species: 967210
type: SpeciesReference

967730
kinetic law: 231111
product: 231098
reactant: 231086
notes: 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
fast: false
reversible: true
type: Reaction

233538
stoichiometry: 1.0
species: 966630
type: SpeciesReference

510079
units: 230126
value: 1.36E-12
type: LocalParameter

234032
stoichiometry: 1.0
species: 965200
type: SpeciesReference

970590
kinetic law: 237996
product: 237984
product: 237972
reactant: 237959
fast: false
reversible: false
type: Reaction

963881
constant: true
size: 1.6667E-18
spatial dimensions: 3.0
type: Compartment

509742
units: 230211
value: 4.2E-12
type: LocalParameter

236336
stoichiometry: 1.0
species: 964701
type: SpeciesReference

510099
units: 230126
value: 1.8E-11
type: LocalParameter

230953
stoichiometry: 1.0
species: 964420
type: SpeciesReference

963861
constant: true
size: 1.0E-12
spatial dimensions: 3.0
type: Compartment

232518
stoichiometry: 1.0
species: 965330
type: SpeciesReference

968990
kinetic law: 234056
product: 234044
product: 234032
reactant: 234020
fast: false
reversible: false
type: Reaction

970490
kinetic law: 237754
product: 237741
reactant: 237729
reactant: 237717
notes: See Hanson and Schulman again, for afterburst rates of phosph.
fast: false
reversible: true
type: Reaction

236675
stoichiometry: 1.0
species: 965240
type: SpeciesReference

236288
stoichiometry: 1.0
species: 965020
type: SpeciesReference

230465
stoichiometry: 1.0
species: 964141
type: SpeciesReference

230735
stoichiometry: 1.0
species: 967190
type: SpeciesReference

231705
stoichiometry: 1.0
species: 964580
type: SpeciesReference

232371
local parameters: 509768
local parameters: 509766
notes: kf*Sos_slash_Grb2*Sos_slash_Sos-kb*Sos_slash_Sos_dot_Grb2
type: KineticLaw

237644
stoichiometry: 1.0
species: 965850
type: SpeciesReference

237790
stoichiometry: 1.0
species: 967250
type: SpeciesReference

233598
local parameters: 509872
local parameters: 509870
notes: kf*CaM_minus_Ca4*AC_slash_AC1-kb*AC_slash_AC1_minus_CaM
type: KineticLaw

510078
units: 230211
value: 3.42E-13
type: LocalParameter

238976
stoichiometry: 1.0
species: 967170
type: SpeciesReference

510097
units: 230090
value: 20.1149425287356
type: LocalParameter

965263
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

230795
stoichiometry: 1.0
species: 964321
type: SpeciesReference

970890
kinetic law: 238722
product: 238710
reactant: 238698
reactant: 238685
notes: 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
fast: false
reversible: true
type: Reaction

230881
stoichiometry: 1.0
species: 964301
type: SpeciesReference

233247
stoichiometry: 1.0
species: 966490
type: SpeciesReference

510005
units: 230126
value: 2.0E-14
type: LocalParameter

238577
local parameters: 510077
notes: k3*CaM_po_Ca_pc_n_minus_CaNAB_slash_dephosph_inhib1_slash_dephosph_inhib1_cplx
type: KineticLaw

235141
stoichiometry: 1.0
species: 965610
type: SpeciesReference

232931
stoichiometry: 1.0
species: 966250
type: SpeciesReference

969150
kinetic law: 234453
product: 234441
product: 234429
reactant: 234417
fast: false
reversible: false
type: Reaction

968910
kinetic law: 233864
product: 233852
reactant: 233840
reactant: 233828
notes: 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
fast: false
reversible: true
type: Reaction

237328
stoichiometry: 1.0
species: 965450
type: SpeciesReference

968710
kinetic law: 233405
product: 233393
reactant: 233381
reactant: 233369
fast: false
reversible: true
type: Reaction

968050
kinetic law: 231875
product: 231862
reactant: 231850
reactant: 231838
notes: 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
fast: false
reversible: true
type: Reaction

239387
stoichiometry: 1.0
species: 966870
type: SpeciesReference

965260
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

509740
units: 230126
value: 0.0
type: LocalParameter

510077
units: 230126
value: 3.4E-13
type: LocalParameter

968610
kinetic law: 233161
product: 233149
reactant: 233137
reactant: 233125
fast: false
reversible: true
type: Reaction

967970
product: 231644
product: 231656
reactant: 231632
reversible: true
product: 231668
notes: 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.
type: Reaction
kinetic law: 231680
fast: false

510006
units: 230211
value: 6.0E-12
type: LocalParameter

965830
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

231474
stoichiometry: 1.0
species: 964561
type: SpeciesReference

509958
units: 230126
value: 6.0E-13
type: LocalParameter

969370
kinetic law: 234984
product: 234972
reactant: 234959
reactant: 234947
notes: 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
fast: false
reversible: true
type: Reaction

233622
stoichiometry: 1.0
species: 966750
type: SpeciesReference

968070
kinetic law: 231911
product: 231899
reactant: 231887
fast: false
reversible: true
type: Reaction

231111
local parameters: 509656
local parameters: 509654
notes: kf*IP3-kb*PLCbeta_slash_Inositol
type: KineticLaw

239303
local parameters: 510115
notes: k3*AC_slash_cAMP_minus_PDE_slash_PDE_slash_PDE_cplx
type: KineticLaw

235760
stoichiometry: 1.0
species: 964820
type: SpeciesReference

232749
stoichiometry: 1.0
species: 966090
type: SpeciesReference

967770
kinetic law: 231196
product: 231184
reactant: 231171
reactant: 231159
notes: Affinity for Gq is > 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
fast: false
reversible: true
type: Reaction

965470
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.5
initial amount: NaN
in compartment: 963861
type: Species

235081
local parameters: 509944
local parameters: 509943
notes: k1*MAPK_slash_craf_minus_1_star_*MAPK_star_-k2*MAPK_star__slash_MAPK_star__minus_feedback_slash_MAPK_star__minus_feedback_cplx
type: KineticLaw

236615
local parameters: 509996
notes: k3*Ras_slash_GEF_star__slash_GEF_star__minus_act_minus_ras_slash_GEF_star__minus_act_minus_ras_cplx
type: KineticLaw

969130
kinetic law: 234405
product: 234393
reactant: 234381
reactant: 234369
notes: 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
fast: false
reversible: true
type: Reaction

236312
stoichiometry: 1.0
species: 964960
type: SpeciesReference

239472
stoichiometry: 1.0
species: 966790
type: SpeciesReference

239061
local parameters: 510097
local parameters: 510095
notes: kcat*AC_slash_AC2_star_*AC_slash_ATP/(Km+AC_slash_ATP)
type: KineticLaw

964181
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

233003
stoichiometry: 1.0
species: 966330
type: SpeciesReference

237413
stoichiometry: 1.0
species: 964121
type: SpeciesReference

238345
stoichiometry: 1.0
species: 965990
type: SpeciesReference

509979
units: 230126
value: 2.5E-11
type: LocalParameter

238140
local parameters: 510059
local parameters: 510057
notes: k1*CaMKII_slash_CaMK_minus_thr306*PP1_minus_active-k2*PP1_minus_active_slash_Deph_minus_thr306_slash_Deph_minus_thr306_cplx
type: KineticLaw

510095
units: 230126
value: 7.0E-12
type: LocalParameter

969330
kinetic law: 234887
product: 234875
reactant: 234863
reactant: 234851
notes: 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
fast: false
reversible: true
type: Reaction

510076
units: 230126
value: 1.36E-12
type: LocalParameter

509768
units: 230126
value: 1.68E-14
type: LocalParameter

232834
local parameters: 509808
local parameters: 509806
notes: kf*CaM_slash_neurogranin*CaM_slash_CaM-kb*CaM_slash_neurogranin_minus_CaM
type: KineticLaw

967230
constant: false
boundary condition: true
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

232677
stoichiometry: 1.0
species: 966110
type: SpeciesReference

967210
constant: false
boundary condition: true
has only substance units: false
initial concentration: 0.02
initial amount: NaN
in compartment: 963861
type: Species

510075
units: 230211
value: 3.42E-13
type: LocalParameter

967630
kinetic law: 230905
product: 230893
reactant: 230881
reactant: 230869
notes: 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.
fast: false
reversible: true
type: Reaction

235675
stoichiometry: 1.0
species: 964840
type: SpeciesReference

237014
stoichiometry: 1.0
species: 966830
type: SpeciesReference

968650
kinetic law: 233259
product: 233247
reactant: 233235
reactant: 233223
notes: 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 < 1 min.
fast: false
reversible: true
type: Reaction

964101
constant: false
boundary condition: false
has only substance units: false
initial concentration: 1.0
initial amount: NaN
in compartment: 963861
type: Species

964081
constant: false
boundary condition: false
has only substance units: false
initial concentration: 2.51883333333333E-19
initial amount: NaN
in compartment: 963861
type: Species

967430
kinetic law: 230440
product: 230428
reactant: 230416
notes: 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.
fast: false
reversible: true
type: Reaction

969770
kinetic law: 235988
product: 235976
reactant: 235964
reactant: 235952
notes: See MKP1-tyr-deph
fast: false
reversible: true
type: Reaction

232092
stoichiometry: 1.0
species: 967150
type: SpeciesReference

233803
stoichiometry: 1.0
species: 966830
type: SpeciesReference

230977
stoichiometry: 1.0
species: 964381
type: SpeciesReference

235808
stoichiometry: 1.0
species: 964880
type: SpeciesReference

236651
stoichiometry: 1.0
species: 965240
type: SpeciesReference

231729
local parameters: 509708
local parameters: 509706
notes: kf*Gq_slash_G_minus_GDP*Gq_slash_mGluR-kb*Gq_slash_Rec_minus_Gq
type: KineticLaw

230489
local parameters: 509600
local parameters: 509598
notes: kf*PKC_slash_PKC_minus_Ca*AA-kb*PKC_slash_PKC_minus_Ca_minus_AA_star_
type: KineticLaw

236264
stoichiometry: 1.0
species: 965020
type: SpeciesReference

231269
stoichiometry: 1.0
species: 964541
type: SpeciesReference

230759
local parameters: 509624
local parameters: 509622
notes: kf*PLA2_slash_PLA2_minus_cytosolic*Ca-kb*PLA2_slash_PLA2_minus_Ca_star_
type: KineticLaw

510008
units: 230126
value: 3.6E-11
type: LocalParameter

232032
local parameters: 509736
local parameters: 509734
notes: kf*Ras_slash_inact_minus_GEF*CaM_minus_Ca4-kb*Ras_slash_CaM_minus_GEF
type: KineticLaw

234429
stoichiometry: 1.0
species: 966710
type: SpeciesReference

237595
stoichiometry: 1.0
species: 967230
type: SpeciesReference

235165
stoichiometry: 1.0
species: 964460
type: SpeciesReference

232396
stoichiometry: 1.0
species: 967190
type: SpeciesReference

234369
stoichiometry: 1.0
species: 966750
type: SpeciesReference

510074
units: 230126
value: 6.7E-13
type: LocalParameter

509956
units: 230211
value: 1.62E-11
type: LocalParameter

509766
units: 230211
value: 2.50002E-14
type: LocalParameter

234056
local parameters: 509907
notes: k3*PKC_minus_active_slash_PKC_minus_inact_minus_GAP_slash_PKC_minus_inact_minus_GAP_cplx
type: KineticLaw

965710
constant: false
boundary condition: false
has only substance units: false
initial concentration: 70.0
initial amount: NaN
in compartment: 963861
type: Species

231814
stoichiometry: 1.0
species: 964840
type: SpeciesReference

231062
stoichiometry: 1.0
species: 964481
type: SpeciesReference

233223
stoichiometry: 1.0
species: 966470
type: SpeciesReference

234140
stoichiometry: 1.0
species: 967210
type: SpeciesReference

966130
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

230771
stoichiometry: 1.0
species: 967030
type: SpeciesReference

964561
constant: false
boundary condition: false
has only substance units: false
initial concentration: 1.0
initial amount: NaN
in compartment: 963861
type: Species

970710
kinetic law: 238285
product: 238273
product: 238261
reactant: 238248
fast: false
reversible: false
type: Reaction

238491
stoichiometry: 1.0
species: 966210
type: SpeciesReference

237620
stoichiometry: 1.0
species: 965730
type: SpeciesReference

969730
kinetic law: 235892
product: 235880
reactant: 235868
reactant: 235856
notes: 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
fast: false
reversible: true
type: Reaction

239570
stoichiometry: 1.0
species: 966790
type: SpeciesReference

509746
units: 230126
value: 1.6667E-15
type: LocalParameter

233574
stoichiometry: 1.0
species: 966690
type: SpeciesReference

238952
stoichiometry: 1.0
species: 966330
type: SpeciesReference

234634
stoichiometry: 1.0
species: 964321
type: SpeciesReference

510073
units: 230126
value: 2.67E-12
type: LocalParameter

231450
stoichiometry: 1.0
species: 964560
type: SpeciesReference

509744
units: 230126
value: 2.5E-13
type: LocalParameter

235784
stoichiometry: 1.0
species: 964880
type: SpeciesReference

231656
stoichiometry: 1.0
species: 964540
type: SpeciesReference

509953
units: 230126
value: 1.92E-10
type: LocalParameter

233646
stoichiometry: 1.0
species: 966750
type: SpeciesReference

236723
stoichiometry: 1.0
species: 965180
type: SpeciesReference

236639
stoichiometry: 1.0
species: 965220
type: SpeciesReference

964540
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

237039
stoichiometry: 1.0
species: 965310
type: SpeciesReference

964541
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

236591
stoichiometry: 1.0
species: 965160
type: SpeciesReference

238297
stoichiometry: 1.0
species: 965790
type: SpeciesReference

232725
stoichiometry: 1.0
species: 966090
type: SpeciesReference

964560
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

230686
stoichiometry: 1.0
species: 964141
type: SpeciesReference

233112
local parameters: 509832
local parameters: 509830
notes: kf*CaNAB_minus_Ca4*CaM_minus_TR2_minus_Ca2-kb*PP2B_slash_CaMCa2_minus_CANAB
type: KineticLaw

239363
stoichiometry: 1.0
species: 966890
type: SpeciesReference

510072
units: 230211
value: 3.336E-13
type: LocalParameter

509764
units: 230126
value: 0.0
type: LocalParameter

236990
stoichiometry: 1.0
species: 965275
type: SpeciesReference

968490
kinetic law: 232834
product: 232822
reactant: 232810
reactant: 232797
notes: 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
fast: false
reversible: true
type: Reaction

232653
stoichiometry: 1.0
species: 966010
type: SpeciesReference

509954
units: 230126
value: 4.8E-11
type: LocalParameter

239219
stoichiometry: 1.0
species: 966650
type: SpeciesReference

966550
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

235587
stoichiometry: 1.0
species: 964800
type: SpeciesReference

968690
kinetic law: 233357
product: 233344
reactant: 233332
reactant: 233320
fast: false
reversible: true
type: Reaction

233731
local parameters: 509884
local parameters: 509882
notes: kf*Gs_minus_alpha*AC_slash_AC1-kb*AC_slash_AC1_minus_Gs
type: KineticLaw

966530
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

239085
stoichiometry: 1.0
species: 966650
type: SpeciesReference

964960
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.224
initial amount: NaN
in compartment: 963861
type: Species

238369
stoichiometry: 1.0
species: 965910
type: SpeciesReference

238455
stoichiometry: 1.0
species: 966070
type: SpeciesReference

965790
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

232810
stoichiometry: 1.0
species: 966010
type: SpeciesReference

510071
units: 230126
value: 3.5E-13
type: LocalParameter

233405
local parameters: 509856
local parameters: 509854
notes: kf*cAMP*PKA_slash_R2C2_minus_cAMP3-kb*PKA_slash_R2C2_minus_cAMP4
type: KineticLaw

968330
kinetic law: 232468
product: 232456
reactant: 232444
reactant: 232432
notes: 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.
fast: false
reversible: true
type: Reaction

963921
constant: false
boundary condition: false
has only substance units: false
initial concentration: 4.91366666666667E-18
initial amount: NaN
in compartment: 963861
type: Species

236240
stoichiometry: 1.0
species: 964820
type: SpeciesReference

509971
units: 230126
value: 4.0E-12
type: LocalParameter

232008
stoichiometry: 1.0
species: 965330
type: SpeciesReference

510117
units: 230126
value: 8.0E-11
type: LocalParameter

237778
stoichiometry: 1.0
species: 965770
type: SpeciesReference

233550
local parameters: 509868
local parameters: 509866
notes: kf*PKA_minus_active*PKA_slash_PKA_minus_inhibitor-kb*PKA_slash_inhibited_minus_PKA
type: KineticLaw

967710
kinetic law: 231074
product: 231062
reactant: 231050
reactant: 231037
notes: 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.
fast: false
reversible: true
type: Reaction

234212
stoichiometry: 1.0
species: 964221
type: SpeciesReference

970870
kinetic law: 238673
product: 238661
product: 238649
reactant: 238637
fast: false
reversible: false
type: Reaction

970030
kinetic law: 236615
product: 236603
product: 236591
reactant: 236579
fast: false
reversible: false
type: Reaction

234658
stoichiometry: 1.0
species: 967010
type: SpeciesReference

969410
kinetic law: 235081
product: 235068
reactant: 235056
reactant: 235044
notes: 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.
fast: false
reversible: true
type: Reaction

509932
units: 230211
value: 1.5E-11
type: LocalParameter

509674
units: 230211
value: 3.0E-11
type: LocalParameter

965200
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

509913
units: 230211
value: 1.02E-13
type: LocalParameter

230332
stoichiometry: 1.0
species: 964121
type: SpeciesReference

231838
stoichiometry: 1.0
species: 964540
type: SpeciesReference

963901
constant: false
boundary condition: false
has only substance units: false
initial concentration: 3.72083333333333E-17
initial amount: NaN
in compartment: 963861
type: Species

968970
kinetic law: 234008
product: 233996
reactant: 233984
reactant: 233972
notes: Rate consts copied from PCK-act-raf This reaction inactivates GAP. The idea is from the Boguski and McCormick review.
fast: false
reversible: true
type: Reaction

965530
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

509951
units: 230126
value: 1.0E-11
type: LocalParameter

235503
local parameters: 509958
local parameters: 509956
notes: k1*MAPK_slash_MAPK*MAPK_slash_MAPKK_star_-k2*MAPK_slash_MAPKK_star__slash_MAPKKtyr_slash_MAPKKtyr_cplx
type: KineticLaw

969290
kinetic law: 234791
product: 234779
reactant: 234767
reactant: 234755
notes: 10 X raise oct 22 12 X raise oct 24 + conversion to k2 =4 * k3
fast: false
reversible: true
type: Reaction

968310
kinetic law: 232420
product: 232407
reactant: 232396
reactant: 232383
notes: 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.
fast: false
reversible: true
type: Reaction

236882
stoichiometry: 1.0
species: 965260
type: SpeciesReference

233465
stoichiometry: 1.0
species: 966570
type: SpeciesReference

234743
local parameters: 509930
notes: k3*PLA2_slash_PIP2_minus_Ca_minus_PLA2_star__slash_kenz_slash_kenz_cplx
type: KineticLaw

238843
stoichiometry: 1.0
species: 966250
type: SpeciesReference

509874
units: 230126
value: 1.0E-13
type: LocalParameter

235189
stoichiometry: 1.0
species: 964460
type: SpeciesReference

509972
units: 230126
value: 1.0E-12
type: LocalParameter

509808
units: 230126
value: 1.0E-12
type: LocalParameter

230869
stoichiometry: 1.0
species: 964121
type: SpeciesReference

510118
units: 230126
value: 2.0E-11
type: LocalParameter

970050
kinetic law: 236663
product: 236651
reactant: 236639
reactant: 236627
notes: From Eccleston et al JBC 268(36)pp27012-19 get Kd < 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.
fast: false
reversible: true
type: Reaction

967190
constant: true
boundary condition: true
has only substance units: false
initial concentration: 0.08
initial amount: NaN
in compartment: 963861
type: Species

967590
kinetic law: 230808
product: 230795
reactant: 230783
reactant: 230771
fast: false
reversible: true
type: Reaction

965510
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

967170
notes: ATP is present in all cells between 2 and 10 mM. See Lehninger.
constant: true
boundary condition: true
has only substance units: false
initial concentration: 5000.0
initial amount: NaN
in compartment: 963861
type: Species

509912
units: 230126
value: 4.0E-12
type: LocalParameter

236156
stoichiometry: 1.0
species: 964960
type: SpeciesReference

237570
stoichiometry: 1.0
species: 965830
type: SpeciesReference

509952
units: 230211
value: 4.8E-11
type: LocalParameter

231546
stoichiometry: 1.0
species: 964581
type: SpeciesReference

231171
stoichiometry: 1.0
species: 964481
type: SpeciesReference

967410
kinetic law: 230404
product: 230392
reactant: 230380
fast: false
reversible: true
type: Reaction

966050
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

965240
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

235276
local parameters: 509950
local parameters: 509949
notes: k1*PIP2*PLCbeta_slash_PLC_minus_Ca-k2*PLCbeta_slash_PLC_minus_Ca_slash_PLC_minus_Ca_slash_PLC_minus_Ca_cplx
type: KineticLaw

509910
units: 230126
value: 1.6E-11
type: LocalParameter

510119
units: 230211
value: 2.1E-13
type: LocalParameter

238188
local parameters: 510061
notes: k3*PP1_minus_active_slash_Deph_minus_thr306_slash_Deph_minus_thr306_cplx
type: KineticLaw

238479
local parameters: 510074
notes: k3*CaM_po_Ca_pc_n_minus_CaNAB_slash_dephosph_neurogranin_slash_dephosph_neurogranin_cplx
type: KineticLaw

509676
units: 230126
value: 1.0E-12
type: LocalParameter

967790
kinetic law: 231245
product: 231233
product: 231221
reactant: 231208
notes: 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
fast: false
reversible: true
type: Reaction

232407
stoichiometry: 1.0
species: 965670
type: SpeciesReference

231305
stoichiometry: 1.0
species: 967190
type: SpeciesReference

965490
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

509930
units: 230126
value: 3.6E-11
type: LocalParameter

965850
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

234128
stoichiometry: 1.0
species: 965120
type: SpeciesReference

239436
stoichiometry: 1.0
species: 966930
type: SpeciesReference

966070
constant: false
boundary condition: false
has only substance units: false
initial concentration: 10.0
initial amount: NaN
in compartment: 963861
type: Species

231790
stoichiometry: 1.0
species: 964660
type: SpeciesReference

969550
kinetic law: 235453
product: 235440
product: 235427
product: 235414
reactant: 235401
fast: false
reversible: false
type: Reaction

969350
kinetic law: 234935
product: 234923
product: 234911
reactant: 234899
fast: false
reversible: false
type: Reaction

233755
stoichiometry: 1.0
species: 966710
type: SpeciesReference

235712
stoichiometry: 1.0
species: 964860
type: SpeciesReference

509970
units: 230211
value: 7.5E-11
type: LocalParameter

509806
units: 230211
value: 3.0E-13
type: LocalParameter

965450
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

232701
stoichiometry: 1.0
species: 966110
type: SpeciesReference

509748
units: 230126
value: 0.0
type: LocalParameter

238273
stoichiometry: 1.0
species: 965910
type: SpeciesReference

509872
units: 230126
value: 1.0E-12
type: LocalParameter

509788
units: 230126
value: 1.0E-13
type: LocalParameter

232116
local parameters: 509744
local parameters: 509742
notes: kf*EGFR_slash_EGFR*EGFR_slash_EGF-kb*EGFR_slash_L_dot_EGFR
type: KineticLaw

970210
kinetic law: 237052
product: 237039
reactant: 237027
reactant: 237014
notes: Same rates as PKA-phosph-I1
fast: false
reversible: true
type: Reaction

967990
kinetic law: 231729
product: 231717
reactant: 231705
reactant: 231692
notes: 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.
fast: false
reversible: true
type: Reaction

965810
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

232164
stoichiometry: 1.0
species: 965411
type: SpeciesReference

236747
stoichiometry: 1.0
species: 965272
type: SpeciesReference

968630
kinetic law: 233210
product: 233197
reactant: 233185
reactant: 233173
fast: false
reversible: true
type: Reaction

231632
stoichiometry: 1.0
species: 964620
type: SpeciesReference

235478
stoichiometry: 1.0
species: 964740
type: SpeciesReference

238405
stoichiometry: 1.0
species: 967270
type: SpeciesReference

967450
kinetic law: 230489
product: 230477
reactant: 230465
reactant: 230452
notes: Schaechter and Benowitz We have to increase Kf for conc scaling Changed kf to 2e-9 on Sept 19, 94. This gives better match.
fast: false
reversible: true
type: Reaction

234188
stoichiometry: 1.0
species: 964221
type: SpeciesReference

236942
stoichiometry: 1.0
species: 965291
type: SpeciesReference

509950
units: 230126
value: 4.0E-11
type: LocalParameter

968930
kinetic law: 233912
product: 233900
reactant: 233888
reactant: 233876
notes: 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
fast: false
reversible: true
type: Reaction

230440
local parameters: 509597
local parameters: 509596
notes: kf*PKC_slash_PKC_minus_Ca_minus_DAG-kb*PKC_slash_PKC_minus_DAG_minus_memb_star_
type: KineticLaw

509650
units: 230211
value: 3.0E-12
type: LocalParameter

509937
units: 230211
value: 3.0E-11
type: LocalParameter

236784
stoichiometry: 1.0
species: 965160
type: SpeciesReference

966610
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.25
initial amount: NaN
in compartment: 963861
type: Species

230186
exponent: -2.0
scale: -6
multipler: 1.0
kind: MOLE
type: SBMLUnit

235453
local parameters: 509954
notes: k3*PLCbeta_slash_PLC_minus_Ca_minus_Gq_slash_PLCb_minus_Ca_minus_Gq_slash_PLCb_minus_Ca_minus_Gq_cplx
type: KineticLaw

237196
local parameters: 510025
notes: k3*Shc_star__dot_Sos_dot_Grb2_slash_Sos_dot_Ras_GEF_slash_Sos_dot_Ras_GEF_cplx
type: KineticLaw

230356
stoichiometry: 1.0
species: 964041
type: SpeciesReference

971110
kinetic law: 239255
product: 239243
reactant: 239231
reactant: 239219
notes: 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
fast: false
reversible: true
type: Reaction

238673
local parameters: 510080
notes: k3*CaM_po_Ca_pc_n_minus_CaNAB_slash_dephosph_minus_PP1_minus_I_star__slash_dephosph_minus_PP1_minus_I_star__cplx
type: KineticLaw

509975
units: 230126
value: 1.0E-12
type: LocalParameter

510029
units: 230211
value: 1.2E-12
type: LocalParameter

235527
stoichiometry: 1.0
species: 964720
type: SpeciesReference

231196
local parameters: 509664
local parameters: 509662
notes: kf*G_star_GTP*PLCbeta_slash_PLC_minus_Ca-kb*PLCbeta_slash_PLC_minus_Ca_minus_Gq
type: KineticLaw

510113
units: 230126
value: 4.0E-11
type: LocalParameter

238128
stoichiometry: 1.0
species: 965950
type: SpeciesReference

233429
stoichiometry: 1.0
species: 965275
type: SpeciesReference

234972
stoichiometry: 1.0
species: 964440
type: SpeciesReference

509670
units: 230211
value: 2.52E-12
type: LocalParameter

237754
local parameters: 510043
local parameters: 510042
notes: k1*CaMKII_slash_CaMKII_minus_thr286*CaMKII_slash_tot_autonomous_CaMKII-k2*CaMKII_slash_tot_autonomous_CaMKII_slash_auton_305_slash_auton_305_cplx
type: KineticLaw

239158
local parameters: 510105
local parameters: 510103
notes: kcat*AC_slash_AC1_minus_Gs*AC_slash_ATP/(Km+AC_slash_ATP)
type: KineticLaw

234718
stoichiometry: 1.0
species: 964141
type: SpeciesReference

966990
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

964480
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.8
initial amount: NaN
in compartment: 963861
type: Species

234236
stoichiometry: 1.0
species: 967210
type: SpeciesReference

232310
stoichiometry: 1.0
species: 965610
type: SpeciesReference

510028
units: 230126
value: 2.0E-13
type: LocalParameter

509936
units: 230126
value: 6.0E-11
type: LocalParameter

239498
local parameters: 510121
notes: k3*AC_slash_PDE1_slash_PDE1_slash_PDE1_cplx
type: KineticLaw

231522
local parameters: 509692
local parameters: 509690
notes: kf*G_star_GTP-kb*G_star_GDP
type: KineticLaw

238722
local parameters: 510082
local parameters: 510081
notes: k1*PP1_slash_I1_star_*PP2A-k2*PP2A_slash_PP2A_minus_dephosph_minus_I1_slash_PP2A_minus_dephosph_minus_I1_cplx
type: KineticLaw

236699
stoichiometry: 1.0
species: 965220
type: SpeciesReference

233441
stoichiometry: 1.0
species: 966570
type: SpeciesReference

235117
stoichiometry: 1.0
species: 964421
type: SpeciesReference

509977
units: 230211
value: 1.98E-12
type: LocalParameter

234767
stoichiometry: 1.0
species: 964361
type: SpeciesReference

509898
units: 230211
value: 3.0E-13
type: LocalParameter

232262
stoichiometry: 1.0
species: 965550
type: SpeciesReference

969750
kinetic law: 235940
product: 235928
product: 235916
reactant: 235904
fast: false
reversible: false
type: Reaction

235414
stoichiometry: 1.0
species: 964121
type: SpeciesReference

964481
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

234092
stoichiometry: 1.0
species: 964201
type: SpeciesReference

231329
stoichiometry: 1.0
species: 964501
type: SpeciesReference

238008
stoichiometry: 1.0
species: 965770
type: SpeciesReference

966910
constant: false
boundary condition: false
has only substance units: false
initial concentration: 2.0
initial amount: NaN
in compartment: 963861
type: Species

970570
kinetic law: 237947
product: 237935
reactant: 237923
reactant: 237911
notes: 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
fast: false
reversible: true
type: Reaction

509652
units: 230126
value: 1.0E-12
type: LocalParameter

966310
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

233779
local parameters: 509888
local parameters: 509886
notes: kf*Gs_minus_alpha*AC_slash_AC2_star_-kb*AC_slash_AC2_star__minus_Gs
type: KineticLaw

510115
units: 230126
value: 1.0E-11
type: LocalParameter

233357
local parameters: 509852
local parameters: 509850
notes: kf*PKA_slash_R2C2_minus_cAMP2*cAMP-kb*PKA_slash_R2C2_minus_cAMP3
type: KineticLaw

231583
stoichiometry: 1.0
species: 967050
type: SpeciesReference

232785
local parameters: 509804
local parameters: 509802
notes: kf*CaM_minus_Ca3*Ca-kb*CaM_minus_Ca4
type: KineticLaw

235736
stoichiometry: 1.0
species: 964840
type: SpeciesReference

509973
units: 230211
value: 7.5E-11
type: LocalParameter

239412
stoichiometry: 1.0
species: 966650
type: SpeciesReference

238321
stoichiometry: 1.0
species: 965990
type: SpeciesReference

234320
stoichiometry: 1.0
species: 966010
type: SpeciesReference

509878
units: 230211
value: 4.99998E-10
type: LocalParameter

970970
kinetic law: 238916
product: 238904
reactant: 238891
reactant: 238879
notes: 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
fast: false
reversible: true
type: Reaction

966330
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

509672
units: 230126
value: 1.0E-12
type: LocalParameter

232858
stoichiometry: 1.0
species: 966070
type: SpeciesReference

238164
stoichiometry: 1.0
species: 965710
type: SpeciesReference

970550
kinetic law: 237899
product: 237887
product: 237874
reactant: 237862
fast: false
reversible: false
type: Reaction

964780
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

509934
units: 230126
value: 2.4E-10
type: LocalParameter

967490
kinetic law: 230563
product: 230551
reactant: 230538
notes: Initial basal levels were set by kf = 1, kb = 20. In model, though, the basal levels of PKC activity are higher.
fast: false
reversible: true
type: Reaction

232188
local parameters: 509752
local parameters: 509750
notes: kf*EGFR_slash_L_dot_EGFR-kb*EGFR_slash_Internal_L_dot_EGFR
type: KineticLaw

237377
stoichiometry: 1.0
species: 965411
type: SpeciesReference

509876
units: 230126
value: 0.0
type: LocalParameter

970230
kinetic law: 237100
product: 237088
product: 237076
reactant: 237064
fast: false
reversible: false
type: Reaction

510116
units: 230211
value: 5.04E-12
type: LocalParameter

234164
stoichiometry: 1.0
species: 966070
type: SpeciesReference

966370
constant: false
boundary condition: false
has only substance units: false
initial concentration: 1.0
initial amount: NaN
in compartment: 963861
type: Species

235650
local parameters: 509963
notes: k3*MAPK_slash_MAPKK_star__slash_MAPKKthr_slash_MAPKKthr_cplx
type: KineticLaw

964740
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

509974
units: 230126
value: 4.0E-12
type: LocalParameter

231498
stoichiometry: 1.0
species: 964541
type: SpeciesReference

966350
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

509896
units: 230126
value: 5.0E-12
type: LocalParameter

236012
stoichiometry: 1.0
species: 964720
type: SpeciesReference

964720
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

233828
stoichiometry: 1.0
species: 966910
type: SpeciesReference

237304
stoichiometry: 1.0
species: 965470
type: SpeciesReference

964760
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

238625
local parameters: 510079
local parameters: 510078
notes: k1*PP1_slash_PP1_minus_I1_star_*CaM_po_Ca_pc_n_minus_CaNAB-k2*CaM_po_Ca_pc_n_minus_CaNAB_slash_dephosph_minus_PP1_minus_I_star__slash_dephosph_minus_PP1_minus_I_star__cplx
type: KineticLaw

967670
kinetic law: 230989
product: 230977
reactant: 230965
reactant: 230953
notes: 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....
fast: false
reversible: true
type: Reaction

236036
local parameters: 509975
notes: k3*MKP_minus_1_slash_MKP1_minus_thr_minus_deph_slash_MKP1_minus_thr_minus_deph_cplx
type: KineticLaw

510056
units: 230126
value: 3.5E-13
type: LocalParameter

238539
stoichiometry: 1.0
species: 966150
type: SpeciesReference

237352
stoichiometry: 1.0
species: 965450
type: SpeciesReference

509602
units: 230126
value: 2.0E-12
type: LocalParameter

230295
stoichiometry: 1.0
species: 967190
type: SpeciesReference

233320
stoichiometry: 1.0
species: 966510
type: SpeciesReference

235856
stoichiometry: 1.0
species: 964720
type: SpeciesReference

230308
stoichiometry: 1.0
species: 963901
type: SpeciesReference

233683
local parameters: 509880
local parameters: 509878
notes: kf*AC_slash_AC2*Gs_minus_alpha-kb*AC_slash_AC2_minus_Gs
type: KineticLaw

239134
stoichiometry: 1.0
species: 966650
type: SpeciesReference

964141
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

510122
units: 230211
value: 1.26E-12
type: LocalParameter

234525
stoichiometry: 1.0
species: 964141
type: SpeciesReference

238746
stoichiometry: 1.0
species: 966190
type: SpeciesReference

510036
units: 230211
value: 2.64084E-13
type: LocalParameter

971150
kinetic law: 239351
product: 239339
reactant: 239327
reactant: 239315
notes: 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.
fast: false
reversible: true
type: Reaction

509714
units: 230211
value: 2.4E-11
type: LocalParameter

237208
stoichiometry: 1.0
species: 965670
type: SpeciesReference

509794
units: 230162
value: 7.2E-11
type: LocalParameter

232919
local parameters: 509816
local parameters: 509814
notes: kf*PP1_slash_I1_star_*PP1_minus_active-kb*PP1_slash_PP1_minus_I1_star_
type: KineticLaw

234839
local parameters: 509936
notes: k3*PLA2_slash_DAG_minus_Ca_minus_PLA2_star__slash_kenz_slash_kenz_cplx
type: KineticLaw

230380
stoichiometry: 1.0
species: 963901
type: SpeciesReference

970850
kinetic law: 238625
product: 238613
reactant: 238601
reactant: 238589
fast: false
reversible: true
type: Reaction

510057
units: 230211
value: 3.432E-13
type: LocalParameter

235637
stoichiometry: 1.0
species: 964740
type: SpeciesReference

969570
kinetic law: 235503
product: 235490
reactant: 235478
reactant: 235466
notes: 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
fast: false
reversible: true
type: Reaction

230832
stoichiometry: 1.0
species: 964301
type: SpeciesReference

230563
local parameters: 509608
local parameters: 509606
notes: kf*PKC_slash_PKC_minus_cytosolic-kb*PKC_slash_PKC_minus_basal_star_
type: KineticLaw

238916
local parameters: 510088
local parameters: 510087
notes: k1*PP1_slash_I1_star_*CaNAB_minus_Ca4-k2*CaNAB_minus_Ca4_slash_dephosph_inhib1_noCaM_slash_dephosph_inhib1_noCaM_cplx
type: KineticLaw

509696
units: 230126
value: 1.0E-16
type: LocalParameter

233308
local parameters: 509848
local parameters: 509846
notes: kf*PKA_slash_R2C2_minus_cAMP*cAMP-kb*PKA_slash_R2C2_minus_cAMP2
type: KineticLaw

971190
kinetic law: 239448
product: 239436
reactant: 239424
reactant: 239412
notes: 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.
fast: false
reversible: true
type: Reaction

966290
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

237088
stoichiometry: 1.0
species: 965275
type: SpeciesReference

971170
kinetic law: 239400
product: 239387
product: 239375
reactant: 239363
fast: false
reversible: false
type: Reaction

237947
local parameters: 510049
local parameters: 510048
notes: k1*CaMKII_slash_CaMKII_minus_thr286_star__minus_CaM*PP1_minus_active-k2*PP1_minus_active_slash_Deph_minus_thr286_slash_Deph_minus_thr286_cplx
type: KineticLaw

235226
local parameters: 509948
notes: k3*MAPK_star__slash_phosph_Sos_slash_phosph_Sos_cplx
type: KineticLaw

966270
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.12
initial amount: NaN
in compartment: 963861
type: Species

510121
units: 230126
value: 1.667E-12
type: LocalParameter

234923
stoichiometry: 1.0
species: 964381
type: SpeciesReference

509604
units: 230126
value: 2.0E-13
type: LocalParameter

965220
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.002
initial amount: NaN
in compartment: 963861
type: Species

234597
local parameters: 509926
local parameters: 509925
notes: k1*PLA2_slash_APC*PLA2_slash_PIP2_minus_PLA2_star_-k2*PLA2_slash_PIP2_minus_PLA2_star__slash_kenz_slash_kenz_cplx
type: KineticLaw

510037
units: 230126
value: 2.4E-11
type: LocalParameter

509642
units: 230211
value: 6.0E-12
type: LocalParameter

235056
stoichiometry: 1.0
species: 964421
type: SpeciesReference

235312
stoichiometry: 1.0
species: 964461
type: SpeciesReference

970354
kinetic law: 237389
product: 237377
product: 237365
reactant: 237352
fast: false
reversible: false
type: Reaction

509918
units: 230126
value: 3.5E-13
type: LocalParameter

233900
stoichiometry: 1.0
species: 964161
type: SpeciesReference

231766
stoichiometry: 1.0
species: 964640
type: SpeciesReference

971230
kinetic law: 239546
product: 239534
reactant: 239522
reactant: 239510
notes: Max activity ~10umol/min/mg in presence of lots of CaM. Affinity is low, 40 uM. k3 = 10, k2 = 40, k1 = (50/40) / 6e5.
fast: false
reversible: true
type: Reaction

236954
local parameters: 510013
local parameters: 510011
notes: k1*PP1_slash_I1*PKA_minus_active-k2*PKA_minus_active_slash_PKA_minus_phosph_minus_I1_slash_PKA_minus_phosph_minus_I1_cplx
type: KineticLaw

231377
stoichiometry: 1.0
species: 964581
type: SpeciesReference

969170
kinetic law: 234501
product: 234489
reactant: 234477
reactant: 234465
notes: 10 x raise oct22 12 x oct 24, set k2 = 4 * k3
fast: false
reversible: true
type: Reaction

233393
stoichiometry: 1.0
species: 966550
type: SpeciesReference

238661
stoichiometry: 1.0
species: 967270
type: SpeciesReference

233040
stoichiometry: 2.0
species: 967190
type: SpeciesReference

965430
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

236360
stoichiometry: 1.0
species: 965040
type: SpeciesReference

238782
stoichiometry: 1.0
species: 966230
type: SpeciesReference

510124
units: 230126
value: 1.0E-11
type: LocalParameter

231025
local parameters: 509648
local parameters: 509646
notes: kf*PLA2_slash_PLA2_star_-kb*PLA2_slash_PLA2_minus_cytosolic
type: KineticLaw

509792
units: 230126
value: 0.0
type: LocalParameter

969190
kinetic law: 234549
product: 234537
product: 234525
reactant: 234513
fast: false
reversible: false
type: Reaction

968090
kinetic law: 231947
product: 231935
reactant: 231923
notes: 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
fast: false
reversible: true
type: Reaction

509938
units: 230126
value: 4.8E-10
type: LocalParameter

510038
units: 230126
value: 6.0E-12
type: LocalParameter

237100
local parameters: 510020
notes: k3*PKA_minus_active_slash_phosph_minus_PDE_slash_phosph_minus_PDE_cplx
type: KineticLaw

968750
kinetic law: 233501
product: 233489
product: 233477
reactant: 233465
fast: false
reversible: true
type: Reaction

236120
stoichiometry: 1.0
species: 964960
type: SpeciesReference

964820
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

969630
kinetic law: 235650
product: 235637
product: 235625
reactant: 235612
fast: false
reversible: false
type: Reaction

509712
units: 230126
value: 1.0E-14
type: LocalParameter

239448
local parameters: 510120
local parameters: 510119
notes: k1*cAMP*AC_slash_PDE1-k2*AC_slash_PDE1_slash_PDE1_slash_PDE1_cplx
type: KineticLaw

510059
units: 230126
value: 1.4E-12
type: LocalParameter

968530
kinetic law: 232919
product: 232907
reactant: 232894
reactant: 232882
notes: K inhib = 1nM from Cohen Ann Rev Bioch 1989, 4 nM from Foukes et al Assume 2 nM. kf /kb = 8.333e-4
fast: false
reversible: true
type: Reaction

509694
units: 230211
value: 6.0E-15
type: LocalParameter

509919
units: 230211
value: 6.0E-13
type: LocalParameter

231426
stoichiometry: 1.0
species: 964540
type: SpeciesReference

969430
kinetic law: 235129
product: 235117
product: 235105
reactant: 235093
fast: false
reversible: false
type: Reaction

238393
stoichiometry: 1.0
species: 966050
type: SpeciesReference

968950
kinetic law: 233960
product: 233948
product: 233936
reactant: 233924
fast: false
reversible: false
type: Reaction

971250
kinetic law: 239594
product: 239582
product: 239570
reactant: 239558
fast: false
reversible: false
type: Reaction

234996
stoichiometry: 1.0
species: 964440
type: SpeciesReference

509606
units: 230126
value: 1.0E-12
type: LocalParameter

510123
units: 230126
value: 4.0E-11
type: LocalParameter

968550
kinetic law: 233016
product: 233003
reactant: 232991
reactant: 232979
notes: 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
fast: false
reversible: true
type: Reaction

238056
stoichiometry: 1.0
species: 965930
type: SpeciesReference

509939
units: 230126
value: 1.2E-10
type: LocalParameter

510039
units: 230211
value: 2.20068E-14
type: LocalParameter

509644
units: 230126
value: 1.0E-13
type: LocalParameter

964800
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

234549
local parameters: 509924
notes: k3*PLA2_slash_PLA2_minus_Ca_star__slash_kenz_slash_kenz_cplx
type: KineticLaw

965290
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

239110
local parameters: 510101
local parameters: 510099
notes: kcat*AC_slash_AC2_minus_Gs*AC_slash_ATP/(Km+AC_slash_ATP)
type: KineticLaw

235916
stoichiometry: 1.0
species: 964700
type: SpeciesReference

964500
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

232298
stoichiometry: 1.0
species: 965590
type: SpeciesReference

966570
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

970310
kinetic law: 237292
product: 237280
product: 237268
reactant: 237256
fast: false
reversible: false
type: Reaction

510031
units: 230126
value: 2.0E-13
type: LocalParameter

238429
local parameters: 510073
local parameters: 510072
notes: k1*CaM_slash_neurogranin_star_*CaM_po_Ca_pc_n_minus_CaNAB-k2*CaM_po_Ca_pc_n_minus_CaNAB_slash_dephosph_neurogranin_slash_dephosph_neurogranin_cplx
type: KineticLaw

509648
units: 230126
value: 0.0
type: LocalParameter

966210
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.001
initial amount: NaN
in compartment: 963861
type: Species

509916
units: 230211
value: 6.12E-14
type: LocalParameter

509798
units: 230211
value: 3.6E-12
type: LocalParameter

238601
stoichiometry: 1.0
species: 967270
type: SpeciesReference

509718
units: 230211
value: 6.0E-12
type: LocalParameter

509842
units: 230211
value: 5.4E-11
type: LocalParameter

510032
units: 230126
value: 1.4E-11
type: LocalParameter

238515
stoichiometry: 1.0
species: 966150
type: SpeciesReference

230588
stoichiometry: 1.0
species: 964101
type: SpeciesReference

964520
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

509804
units: 230126
value: 1.0E-11
type: LocalParameter

230223
exponent: 2.0
scale: 0
multipler: 1.0
kind: LITRE
type: SBMLUnit

231401
stoichiometry: 1.0
species: 964561
type: SpeciesReference

233344
stoichiometry: 1.0
species: 966530
type: SpeciesReference

239024
stoichiometry: 1.0
species: 967170
type: SpeciesReference

966590
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

509882
units: 230211
value: 1.26E-10
type: LocalParameter

966230
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

969850
kinetic law: 236180
product: 236168
reactant: 236156
reactant: 236144
notes: 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.
fast: false
reversible: true
type: Reaction

238092
local parameters: 510056
notes: k3*PP1_minus_active_slash_Deph_minus_thr305_slash_Deph_minus_thr305_cplx
type: KineticLaw

965291
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

238200
stoichiometry: 1.0
species: 965770
type: SpeciesReference

509628
units: 230126
value: 5.0E-13
type: LocalParameter

234104
local parameters: 509910
local parameters: 509908
notes: k1*Ras_slash_inact_minus_GEF*PKC_minus_active-k2*PKC_minus_active_slash_PKC_minus_act_minus_GEF_slash_PKC_minus_act_minus_GEF_cplx
type: KineticLaw

964501
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

234441
stoichiometry: 1.0
species: 967210
type: SpeciesReference

509666
units: 230126
value: 1.33E-14
type: LocalParameter

964880
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

970330
kinetic law: 237340
product: 237328
reactant: 237316
reactant: 237304
notes: 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.
fast: false
reversible: true
type: Reaction

238116
stoichiometry: 1.0
species: 965910
type: SpeciesReference

234068
stoichiometry: 1.0
species: 965100
type: SpeciesReference

234815
stoichiometry: 1.0
species: 964141
type: SpeciesReference

235336
local parameters: 509951
notes: k3*PLCbeta_slash_PLC_minus_Ca_slash_PLC_minus_Ca_slash_PLC_minus_Ca_cplx
type: KineticLaw

509917
units: 230126
value: 1.4E-12
type: LocalParameter

236108
stoichiometry: 1.0
species: 964641
type: SpeciesReference

509646
units: 230126
value: 1.7E-13
type: LocalParameter

966970
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

510033
units: 230090
value: 97.2222222222222
type: LocalParameter

964521
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

969830
kinetic law: 236132
product: 236120
product: 236108
reactant: 236096
fast: false
reversible: false
type: Reaction

966250
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

509608
units: 230126
value: 5.0E-11
type: LocalParameter

235375
stoichiometry: 1.0
species: 964520
type: SpeciesReference

233137
stoichiometry: 1.0
species: 966330
type: SpeciesReference

237064
stoichiometry: 1.0
species: 965310
type: SpeciesReference

237160
stoichiometry: 1.0
species: 965370
type: SpeciesReference

964581
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

966930
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

966890
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

966510
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

237984
stoichiometry: 1.0
species: 965910
type: SpeciesReference

232493
stoichiometry: 1.0
species: 965670
type: SpeciesReference

234381
stoichiometry: 1.0
species: 967210
type: SpeciesReference

967810
kinetic law: 231293
product: 231281
reactant: 231269
reactant: 231257
notes: 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.
fast: false
reversible: true
type: Reaction

239170
stoichiometry: 1.0
species: 967170
type: SpeciesReference

233707
stoichiometry: 1.0
species: 966690
type: SpeciesReference

231001
stoichiometry: 1.0
species: 964420
type: SpeciesReference

965890
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

509914
units: 230126
value: 2.34E-12
type: LocalParameter

969210
kinetic law: 234597
product: 234585
reactant: 234573
reactant: 234561
notes: 10 X raise oct 22 12 X further raise oct 24 to allow for correct conc of enzyme
fast: false
reversible: true
type: Reaction

970910
kinetic law: 238770
product: 238758
product: 238746
reactant: 238734
fast: false
reversible: false
type: Reaction

236567
local parameters: 509995
local parameters: 509994
notes: k1*Ras_slash_GDP_minus_Ras*Ras_slash_GEF_star_-k2*Ras_slash_GEF_star__slash_GEF_star__minus_act_minus_ras_slash_GEF_star__minus_act_minus_ras_cplx
type: KineticLaw

234296
local parameters: 509917
local parameters: 509916
notes: k1*CaM_slash_neurogranin_minus_CaM*PKC_minus_active-k2*PKC_minus_active_slash_PKC_minus_phosph_minus_ng_minus_CaM_slash_PKC_minus_phosph_minus_ng_minus_CaM_cplx
type: KineticLaw

509840
units: 230126
value: 1.0E-12
type: LocalParameter

509796
units: 230126
value: 7.2E-11
type: LocalParameter

965870
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

237607
local parameters: 510038
notes: k3*CaMKII_slash_tot_CaM_CaMKII_slash_CaM_act_305_slash_CaM_act_305_cplx
type: KineticLaw

510034
units: 230126
value: 5.7E-11
type: LocalParameter

509716
units: 230126
value: 5.0E-13
type: LocalParameter

231353
stoichiometry: 1.0
species: 964580
type: SpeciesReference

509880
units: 230126
value: 1.0E-12
type: LocalParameter

969230
kinetic law: 234646
product: 234634
product: 234621
reactant: 234609
fast: false
reversible: false
type: Reaction

968210
kinetic law: 232188
product: 232176
reactant: 232164
notes: 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
fast: false
reversible: true
type: Reaction

236978
stoichiometry: 1.0
species: 966210
type: SpeciesReference

509802
units: 230211
value: 4.65E-13
type: LocalParameter

510120
units: 230126
value: 6.67E-12
type: LocalParameter

231742
stoichiometry: 1.0
species: 964600
type: SpeciesReference

964580
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.3
initial amount: NaN
in compartment: 963861
type: Species

964840
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

233064
local parameters: 509828
local parameters: 509826
notes: kf*PP2B_slash_CaNAB*Ca^2-kb*PP2B_slash_CaNAB_minus_Ca2
type: KineticLaw

238032
stoichiometry: 1.0
species: 965930
type: SpeciesReference

509800
units: 230126
value: 1.0E-11
type: LocalParameter

509698
units: 230211
value: 1.68E-11
type: LocalParameter

237899
local parameters: 510047
notes: k3*CaMKII_slash_tot_autonomous_CaMKII_slash_auton_286_slash_auton_286_cplx
type: KineticLaw

233984
stoichiometry: 1.0
species: 967210
type: SpeciesReference

509915
units: 230126
value: 5.8E-13
type: LocalParameter

965750
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

236808
local parameters: 510005
notes: k3*Ras_slash_CaM_minus_GEF_slash_CaM_minus_GEF_minus_act_minus_ras_slash_CaM_minus_GEF_minus_act_minus_ras_cplx
type: KineticLaw

238891
stoichiometry: 1.0
species: 966330
type: SpeciesReference

509668
units: 230211
value: 0.0
type: LocalParameter

231680
local parameters: 509704
local parameters: 509702
notes: kf*Gq_slash_Rec_minus_Glu_minus_Gq-kb*G_star_GTP*BetaGamma*Gq_slash_Rec_minus_Glu
type: KineticLaw

971130
kinetic law: 239303
product: 239291
product: 239279
reactant: 239267
fast: false
reversible: false
type: Reaction

510035
units: 230090
value: 19.7916666666667
type: LocalParameter

970950
kinetic law: 238867
product: 238855
product: 238843
reactant: 238831
fast: false
reversible: false
type: Reaction

237124
stoichiometry: 1.0
species: 965350
type: SpeciesReference

239546
local parameters: 510123
local parameters: 510122
notes: k1*cAMP*AC_slash_CaM_dot_PDE1-k2*AC_slash_CaM_dot_PDE1_slash_CaM_dot_PDE1_slash_CaM_dot_PDE1_cplx
type: KineticLaw

232882
stoichiometry: 1.0
species: 966210
type: SpeciesReference

235988
local parameters: 509974
local parameters: 509973
notes: k1*MAPK_star_*MKP_minus_1-k2*MKP_minus_1_slash_MKP1_minus_thr_minus_deph_slash_MKP1_minus_thr_minus_deph_cplx
type: KineticLaw

964860
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

232567
stoichiometry: 1.0
species: 965790
type: SpeciesReference

970110
kinetic law: 236808
product: 236796
product: 236784
reactant: 236771
fast: false
reversible: false
type: Reaction

509622
units: 230211
value: 1.00002E-12
type: LocalParameter

235880
stoichiometry: 1.0
species: 964920
type: SpeciesReference

236216
stoichiometry: 1.0
species: 964960
type: SpeciesReference

230538
stoichiometry: 1.0
species: 964101
type: SpeciesReference

967650
kinetic law: 230941
product: 230929
reactant: 230917
notes: 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
fast: false
reversible: true
type: Reaction

233852
stoichiometry: 1.0
species: 966950
type: SpeciesReference

969250
kinetic law: 234694
product: 234682
reactant: 234670
reactant: 234658
notes: 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.
fast: false
reversible: true
type: Reaction

234465
stoichiometry: 1.0
species: 967010
type: SpeciesReference

238224
stoichiometry: 1.0
species: 965970
type: SpeciesReference

969270
kinetic law: 234743
product: 234730
product: 234718
reactant: 234706
fast: false
reversible: false
type: Reaction

235563
stoichiometry: 1.0
species: 964720
type: SpeciesReference

964161
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

967010
notes: 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.
constant: true
boundary condition: true
has only substance units: false
initial concentration: 30.0
initial amount: NaN
in compartment: 963861
type: Species

237486
stoichiometry: 1.0
species: 964461
type: SpeciesReference

238879
stoichiometry: 1.0
species: 966210
type: SpeciesReference

967610
kinetic law: 230857
product: 230844
reactant: 230832
reactant: 230820
fast: false
reversible: true
type: Reaction

969590
kinetic law: 235551
product: 235539
product: 235527
reactant: 235515
fast: false
reversible: false
type: Reaction

233028
stoichiometry: 1.0
species: 966370
type: SpeciesReference

967750
kinetic law: 231147
product: 231135
reactant: 231123
notes: 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 <= 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
fast: false
reversible: true
type: Reaction

232456
stoichiometry: 1.0
species: 965690
type: SpeciesReference

509774
units: 230211
value: 1.2E-11
type: LocalParameter

965690
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

230662
local parameters: 509616
local parameters: 509614
notes: kf*PKC_slash_PKC_minus_cytosolic*DAG-kb*PKC_slash_PKC_minus_DAG
type: KineticLaw

509828
units: 230126
value: 1.0E-12
type: LocalParameter

237717
stoichiometry: 1.0
species: 965790
type: SpeciesReference

964121
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

966090
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

509848
units: 230126
value: 3.3E-11
type: LocalParameter

232359
stoichiometry: 1.0
species: 965570
type: SpeciesReference

236192
stoichiometry: 1.0
species: 965000
type: SpeciesReference

234670
stoichiometry: 1.0
species: 964341
type: SpeciesReference

967690
kinetic law: 231025
product: 231013
reactant: 231001
fast: false
reversible: true
type: Reaction

231159
stoichiometry: 1.0
species: 964541
type: SpeciesReference

237814
stoichiometry: 1.0
species: 965730
type: SpeciesReference

231899
stoichiometry: 1.0
species: 965100
type: SpeciesReference

970370
product: 237426
notes: 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.
type: Reaction
modifier: 237438
kinetic law: 237450
reversible: false
fast: false
product: 237413
reactant: 237401

510011
units: 230211
value: 6.0E-12
type: LocalParameter

970070
kinetic law: 236711
product: 236699
product: 236687
reactant: 236675
fast: false
reversible: false
type: Reaction

509624
units: 230126
value: 1.0E-13
type: LocalParameter

239522
stoichiometry: 1.0
species: 966950
type: SpeciesReference

231935
stoichiometry: 1.0
species: 965180
type: SpeciesReference

237148
local parameters: 510023
local parameters: 510021
notes: k1*Ras_slash_GDP_minus_Ras*Shc_star__dot_Sos_dot_Grb2-k2*Shc_star__dot_Sos_dot_Grb2_slash_Sos_dot_Ras_GEF_slash_Sos_dot_Ras_GEF_cplx
type: KineticLaw

232543
stoichiometry: 1.0
species: 965730
type: SpeciesReference

236458
stoichiometry: 1.0
species: 965080
type: SpeciesReference

967130
notes: 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.
constant: true
boundary condition: true
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

237232
stoichiometry: 1.0
species: 965430
type: SpeciesReference

235964
stoichiometry: 1.0
species: 964900
type: SpeciesReference

509844
units: 230126
value: 3.3E-11
type: LocalParameter

233088
stoichiometry: 1.0
species: 966110
type: SpeciesReference

236918
stoichiometry: 1.0
species: 966190
type: SpeciesReference

231996
stoichiometry: 1.0
species: 965100
type: SpeciesReference

232979
stoichiometry: 2.0
species: 967190
type: SpeciesReference

237292
local parameters: 510028
notes: k3*EGFR_slash_L_dot_EGFR_slash_phosph_PLC_g_slash_phosph_PLC_g_cplx
type: KineticLaw

237510
local parameters: 510035
local parameters: 510034
notes: kcat*PLC_g_slash_Ca_dot_PLC_g_star_*PIP2/(Km+PIP2)
type: KineticLaw

970390
modifier: 237498
type: Reaction
reversible: false
product: 237474
fast: false
product: 237486
reactant: 237462
kinetic law: 237510
notes: 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.

969650
kinetic law: 235700
product: 235688
reactant: 235675
reactant: 235662
notes: 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
fast: false
reversible: true
type: Reaction

968730
kinetic law: 233453
product: 233441
product: 233429
reactant: 233417
notes: This has to be fast, as the activation of PKA by cAMP is also fast. kf was 10
fast: false
reversible: true
type: Reaction

970090
kinetic law: 236759
product: 236747
reactant: 236735
reactant: 236723
notes: Kinetics same as GEF-bg_act-ras
fast: false
reversible: true
type: Reaction

234272
stoichiometry: 1.0
species: 967210
type: SpeciesReference

967150
constant: true
boundary condition: true
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

232201
stoichiometry: 1.0
species: 965570
type: SpeciesReference

232616
stoichiometry: 1.0
species: 965710
type: SpeciesReference

231245
local parameters: 509668
local parameters: 509666
notes: kf*PLCbeta_slash_PLC_minus_Ca_minus_Gq-kb*G_star_GDP*PLCbeta_slash_PLC_minus_Ca
type: KineticLaw

510010
units: 230126
value: 9.0E-12
type: LocalParameter

509772
units: 230126
value: 1.0E-11
type: LocalParameter

239267
stoichiometry: 1.0
species: 966850
type: SpeciesReference

236543
stoichiometry: 1.0
species: 965120
type: SpeciesReference

234609
stoichiometry: 1.0
species: 964340
type: SpeciesReference

963941
constant: false
boundary condition: false
has only substance units: false
initial concentration: 1.75E-16
initial amount: NaN
in compartment: 963861
type: Species

234863
stoichiometry: 1.0
species: 964381
type: SpeciesReference

509826
units: 230162
value: 1.0008E-8
type: LocalParameter

965910
constant: false
boundary condition: false
has only substance units: false
initial concentration: 1.8
initial amount: NaN
in compartment: 963861
type: Species

968770
kinetic law: 233550
product: 233538
reactant: 233526
reactant: 233514
notes: 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
fast: false
reversible: true
type: Reaction

969610
kinetic law: 235599
product: 235587
reactant: 235575
reactant: 235563
notes: Rate consts same as for MAPKKtyr.
fast: false
reversible: true
type: Reaction

510050
units: 230126
value: 3.5E-13
type: LocalParameter

239315
stoichiometry: 1.0
species: 966650
type: SpeciesReference

236820
stoichiometry: 1.0
species: 965100
type: SpeciesReference

969810
kinetic law: 236084
product: 236072
reactant: 236060
reactant: 236048
notes: See parent PPhosphatase2A for parms
fast: false
reversible: true
type: Reaction

509846
units: 230211
value: 5.4E-11
type: LocalParameter

510030
units: 230126
value: 8.0E-13
type: LocalParameter

963961
constant: false
boundary condition: false
has only substance units: false
initial concentration: 1.3896E-17
initial amount: NaN
in compartment: 963861
type: Species

236494
stoichiometry: 1.0
species: 965160
type: SpeciesReference

237874
stoichiometry: 1.0
species: 965750
type: SpeciesReference

233948
stoichiometry: 1.0
species: 967210
type: SpeciesReference

509626
units: 230211
value: 1.2E-15
type: LocalParameter

237546
stoichiometry: 1.0
species: 965830
type: SpeciesReference

233173
stoichiometry: 1.0
species: 965330
type: SpeciesReference

967950
kinetic law: 231620
product: 231608
reactant: 231596
reactant: 231583
notes: 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
fast: false
reversible: true
type: Reaction

965180
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.2
initial amount: NaN
in compartment: 963861
type: Species

237923
stoichiometry: 1.0
species: 965910
type: SpeciesReference

968150
kinetic law: 232068
product: 232056
reactant: 232044
fast: false
reversible: true
type: Reaction

230917
stoichiometry: 1.0
species: 964141
type: SpeciesReference

234489
stoichiometry: 1.0
species: 964320
type: SpeciesReference

234947
stoichiometry: 1.0
species: 964281
type: SpeciesReference

238248
stoichiometry: 1.0
species: 965970
type: SpeciesReference

965000
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

971090
kinetic law: 239206
modifier: 239194
product: 239182
reactant: 239170
fast: false
reversible: false
type: Reaction

235202
stoichiometry: 1.0
species: 965590
type: SpeciesReference

239243
stoichiometry: 1.0
species: 966850
type: SpeciesReference

230626
stoichiometry: 1.0
species: 964101
type: SpeciesReference

509790
units: 230126
value: 3.0E-15
type: LocalParameter

234573
stoichiometry: 1.0
species: 964321
type: SpeciesReference

510013
units: 230126
value: 3.6E-11
type: LocalParameter

235032
local parameters: 509942
notes: k3*MAPK_star__slash_MAPK_star__slash_MAPK_star__cplx
type: KineticLaw

239582
stoichiometry: 1.0
species: 966950
type: SpeciesReference

510093
units: 230090
value: 20.0
type: LocalParameter

968531
kinetic law: 232967
product: 232955
product: 232943
reactant: 232931
notes: Let us assume that the equil in this case is very far over to the right. This is probably safe.
fast: false
reversible: true
type: Reaction

968470
kinetic law: 232785
product: 232773
reactant: 232761
reactant: 232749
notes: Use K3 = 21.5 uM here from Stemmer and Klee table 3. kb/kf =21.5 * 6e5 so kf = 7.75e-7, kb = 10
fast: false
reversible: true
type: Reaction

509822
units: 230162
value: 3.6E-12
type: LocalParameter

968170
kinetic law: 232116
product: 232104
reactant: 232092
reactant: 232080
notes: 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
fast: false
reversible: true
type: Reaction

233876
stoichiometry: 1.0
species: 964641
type: SpeciesReference

231098
stoichiometry: 1.0
species: 967070
type: SpeciesReference

509770
units: 230211
value: 1.8E-10
type: LocalParameter

510052
units: 230211
value: 3.432E-13
type: LocalParameter

232335
stoichiometry: 1.0
species: 965550
type: SpeciesReference

968130
kinetic law: 232032
product: 232020
reactant: 232008
reactant: 231996
notes: 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
fast: false
reversible: true
type: Reaction

234501
local parameters: 509923
local parameters: 509922
notes: k1*PLA2_slash_APC*PLA2_slash_PLA2_minus_Ca_star_-k2*PLA2_slash_PLA2_minus_Ca_star__slash_kenz_slash_kenz_cplx
type: KineticLaw

230989
local parameters: 509644
local parameters: 509642
notes: kf*PLA2_slash_PLA2_star_*Ca-kb*PLA2_slash_PLA2_star__minus_Ca
type: KineticLaw

230513
stoichiometry: 1.0
species: 963921
type: SpeciesReference

509824
units: 230126
value: 1.0E-12
type: LocalParameter

231135
stoichiometry: 1.0
species: 967090
type: SpeciesReference

965020
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

970510
kinetic law: 237802
product: 237790
product: 237778
reactant: 237766
fast: false
reversible: false
type: Reaction

234417
stoichiometry: 1.0
species: 964261
type: SpeciesReference

237838
stoichiometry: 1.0
species: 965890
type: SpeciesReference

233791
stoichiometry: 1.0
species: 966870
type: SpeciesReference

237462
stoichiometry: 1.0
species: 967110
type: SpeciesReference

965040
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

970530
kinetic law: 237850
product: 237838
reactant: 237826
reactant: 237814
fast: false
reversible: true
type: Reaction

233283
stoichiometry: 1.0
species: 966650
type: SpeciesReference

238807
stoichiometry: 1.0
species: 966310
type: SpeciesReference

230416
stoichiometry: 1.0
species: 964041
type: SpeciesReference

231281
stoichiometry: 1.0
species: 964521
type: SpeciesReference

965080
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

509750
units: 230126
value: 2.0E-15
type: LocalParameter

966950
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

233210
local parameters: 509840
local parameters: 509838
notes: kf*CaM_minus_Ca4*CaNAB_minus_Ca4-kb*PP2B_slash_CaMCa4_minus_CaNAB
type: KineticLaw

509710
units: 230211
value: 6.0E-11
type: LocalParameter

232432
stoichiometry: 1.0
species: 967190
type: SpeciesReference

230271
exponent: 1.0
scale: -6
multipler: 1.0
kind: MOLE
type: SBMLUnit

509692
units: 230126
value: 0.0
type: LocalParameter

238649
stoichiometry: 1.0
species: 966250
type: SpeciesReference

235832
stoichiometry: 1.0
species: 964840
type: SpeciesReference

968110
kinetic law: 231983
product: 231971
reactant: 231959
notes: Assume a reasonably good rate for dephosphorylating it, 1/sec
fast: false
reversible: true
type: Reaction

232225
stoichiometry: 1.0
species: 965350
type: SpeciesReference

970930
kinetic law: 238819
product: 238807
reactant: 238795
reactant: 238782
notes: k1 changed from 3.3e-6 to 6.6e-6
fast: false
reversible: true
type: Reaction

509620
units: 230126
value: 2.0E-12
type: LocalParameter

237693
stoichiometry: 1.0
species: 967230
type: SpeciesReference

232955
stoichiometry: 1.0
species: 966190
type: SpeciesReference

510015
units: 230126
value: 9.0E-12
type: LocalParameter

965770
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

510091
units: 230126
value: 1.8E-11
type: LocalParameter

236845
stoichiometry: 1.0
species: 965290
type: SpeciesReference

235940
local parameters: 509972
notes: k3*MKP_minus_1_slash_MKP1_minus_tyr_minus_deph_slash_MKP1_minus_tyr_minus_deph_cplx
type: KineticLaw

236506
stoichiometry: 1.0
species: 965060
type: SpeciesReference

509600
units: 230126
value: 1.0E-13
type: LocalParameter

231875
local parameters: 509720
local parameters: 509718
notes: kf*BetaGamma*Ras_slash_inact_minus_GEF-kb*Ras_slash_GEF_minus_Gprot_minus_bg
type: KineticLaw

231959
stoichiometry: 1.0
species: 965200
type: SpeciesReference

237256
stoichiometry: 1.0
species: 965430
type: SpeciesReference

236434
stoichiometry: 1.0
species: 965180
type: SpeciesReference

510054
units: 230126
value: 1.4E-12
type: LocalParameter

965730
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

509820
units: 230211
value: 0.0
type: LocalParameter

231971
stoichiometry: 1.0
species: 965220
type: SpeciesReference

234308
stoichiometry: 1.0
species: 964241
type: SpeciesReference

230601
stoichiometry: 1.0
species: 964021
type: SpeciesReference

233197
stoichiometry: 1.0
species: 966450
type: SpeciesReference

236470
local parameters: 509992
local parameters: 509991
notes: k1*Ras_slash_GDP_minus_Ras*Ras_slash_GEF_minus_Gprot_minus_bg-k2*Ras_slash_GEF_minus_Gprot_minus_bg_slash_GEF_minus_bg_act_minus_ras_slash_GEF_minus_bg_act_minus_ras_cplx
type: KineticLaw

964201
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 963861
type: Species

237850
local parameters: 510046
local parameters: 510045
notes: k1*CaMKII_slash_CaMKII_minus_CaM*CaMKII_slash_tot_autonomous_CaMKII-k2*CaMKII_slash_tot_autonomous_CaMKII_slash_auton_286_slash_auton_286_cplx
type: KineticLaw

969990
kinetic law: 236519
product: 236506
product: 236494
reactant: 236482
fast: false
reversible: false
type: Reaction

234887
local parameters: 509938
local parameters: 509937
notes: k1*PLA2_slash_APC*PLA2_slash_PLA2_star__minus_Ca-k2*PLA2_slash_PLA2_star__minus_Ca_slash_kenz_slash_kenz_cplx
type: KineticLaw

233924
stoichiometry: 1.0
species: 964161
type: SpeciesReference

239339
stoichiometry: 1.0
species: 966890
type: SpeciesReference

233514
stoichiometry: 1.0
species: 965275
type: SpeciesReference

509690
units: 230126
value: 1.33E-14
type: LocalParameter

236385
stoichiometry: 1.0
species: 965040
type: SpeciesReference

231221
stoichiometry: 1.0
species: 964560
type: SpeciesReference