432127
stoichiometry: 1.0
species: 402137
type: SpeciesReference

434205
stoichiometry: 1.0
species: 403757
type: SpeciesReference

404737
kinetic law: 425679
product: 425666
reactant: 425654
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

428075
stoichiometry: 1.0
species: 403537
type: SpeciesReference

427967
stoichiometry: 1.0
species: 402137
type: SpeciesReference

568792
units: 424878
value: 1.5E-16
type: LocalParameter

428548
stoichiometry: 1.0
species: 400637
type: SpeciesReference

430460
stoichiometry: 1.0
species: 402677
type: SpeciesReference

432055
stoichiometry: 1.0
species: 403737
type: SpeciesReference

428752
local parameters: 569093
local parameters: 569092
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

428825
stoichiometry: 1.0
species: 404297
type: SpeciesReference

428692
stoichiometry: 1.0
species: 404297
type: SpeciesReference

429977
local parameters: 569142
notes: k3*MAPK_star__slash_phosph_Sos_slash_phosph_Sos_cplx
type: KineticLaw

427335
stoichiometry: 1.0
species: 402977
type: SpeciesReference

568791
units: 424878
value: 1.5E-15
type: LocalParameter

426886
stoichiometry: 1.0
species: 402497
type: SpeciesReference

405697
kinetic law: 427894
product: 427882
reactant: 427870
reactant: 427857
fast: false
reversible: true
type: Reaction

429298
local parameters: 569115
notes: k3*PLA2_slash_PLA2_minus_Ca_star__slash_kenz_slash_kenz_cplx
type: KineticLaw

433431
stoichiometry: 1.0
species: 403117
type: SpeciesReference

429819
stoichiometry: 1.0
species: 401037
type: SpeciesReference

427481
stoichiometry: 1.0
species: 402797
type: SpeciesReference

429576
stoichiometry: 1.0
species: 400897
type: SpeciesReference

428935
stoichiometry: 1.0
species: 400697
type: SpeciesReference

568794
units: 424878
value: 1.5E-16
type: LocalParameter

432501
stoichiometry: 1.0
species: 404177
type: SpeciesReference

427238
stoichiometry: 1.0
species: 403017
type: SpeciesReference

426024
local parameters: 568862
local parameters: 568859
notes: kf*G_star_GDP*BetaGamma-kb*Gq_slash_G_minus_GDP
type: KineticLaw

405657
kinetic law: 427797
product: 427785
reactant: 427773
reactant: 427760
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

433890
stoichiometry: 1.0
species: 403237
type: SpeciesReference

568793
units: 424962
value: 9.000045E-19
type: LocalParameter

430828
local parameters: 569177
local parameters: 569174
notes: k1*MAPK_slash_MAPKK_minus_ser*MAPK_slash_Raf_star__minus_GTP_minus_Ras-k2*MAPK_slash_Raf_star__minus_GTP_minus_Ras_slash_Raf_star__minus_GTP_minus_Ras_dot_2_slash_Raf_star__minus_GTP_minus_Ras_dot_2_cplx
type: KineticLaw

427857
stoichiometry: 1.0
species: 403417
type: SpeciesReference

426170
stoichiometry: 1.0
species: 401357
type: SpeciesReference

407077
kinetic law: 431222
product: 431210
reactant: 431198
reactant: 431186
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

433623
stoichiometry: 1.0
species: 403117
type: SpeciesReference

402457
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

430145
stoichiometry: 1.0
species: 401177
type: SpeciesReference

406057
kinetic law: 428704
product: 428692
product: 428680
reactant: 428668
fast: false
reversible: false
type: Reaction

433587
stoichiometry: 1.0
species: 403157
type: SpeciesReference

568858
units: 424962
value: 0.0
type: LocalParameter

432585
stoichiometry: 1.0
species: 402717
type: SpeciesReference

433298
stoichiometry: 1.0
species: 402597
type: SpeciesReference

401057
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

425827
local parameters: 568846
local parameters: 568843
notes: kf*PLCbeta_slash_PLC*G_star_GTP-kb*PLCbeta_slash_PLC_minus_Gq
type: KineticLaw

407637
kinetic law: 432597
product: 432585
reactant: 432573
reactant: 432561
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

401157
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

569131
units: 424962
value: 2.925045E-15
type: LocalParameter

434072
stoichiometry: 1.0
species: 403557
type: SpeciesReference

429140
stoichiometry: 1.0
species: 400737
type: SpeciesReference

403097
constant: false
boundary condition: false
has only substance units: false
initial concentration: 1.8
initial amount: NaN
in compartment: 400538
type: Species

569120
units: 424878
value: 2.16E-13
type: LocalParameter

429214
stoichiometry: 1.0
species: 404077
type: SpeciesReference

431860
stoichiometry: 1.0
species: 401917
type: SpeciesReference

568859
units: 424962
value: 9.000045E-15
type: LocalParameter

431354
stoichiometry: 1.0
species: 401777
type: SpeciesReference

426134
stoichiometry: 1.0
species: 401337
type: SpeciesReference

425292
local parameters: 568798
local parameters: 568795
notes: kf*PLA2_slash_PLA2_minus_cytosolic*Ca-kb*PLA2_slash_PLA2_minus_Ca_star_
type: KineticLaw

431608
local parameters: 569207
local parameters: 569204
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

402417
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

426765
stoichiometry: 1.0
species: 402237
type: SpeciesReference

407677
kinetic law: 432693
product: 432681
reactant: 432669
reactant: 432657
fast: false
reversible: true
type: Reaction

401097
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.8
initial amount: NaN
in compartment: 400538
type: Species

569132
units: 424878
value: 6.0E-14
type: LocalParameter

428584
stoichiometry: 1.0
species: 403977
type: SpeciesReference

406097
kinetic law: 428801
product: 428789
product: 428776
reactant: 428764
fast: false
reversible: false
type: Reaction

568795
units: 424962
value: 1.499985E-15
type: LocalParameter

430424
stoichiometry: 1.0
species: 402837
type: SpeciesReference

568798
units: 424878
value: 1.5E-16
type: LocalParameter

404337
constant: false
boundary condition: true
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

425877
local parameters: 568850
local parameters: 568847
notes: kf*Ca*PLCbeta_slash_PLC_minus_Gq-kb*PLCbeta_slash_PLC_minus_Ca_minus_Gq
type: KineticLaw

427129
stoichiometry: 1.0
species: 402637
type: SpeciesReference

405377
kinetic law: 427141
product: 427129
reactant: 427117
reactant: 427105
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

426802
stoichiometry: 1.0
species: 402437
type: SpeciesReference

434313
stoichiometry: 1.0
species: 403697
type: SpeciesReference

406957
kinetic law: 430930
product: 430918
reactant: 430906
reactant: 430894
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

402237
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

430194
local parameters: 569151
notes: k3*PLCbeta_slash_PLC_minus_Ca_minus_Gq_slash_PLCb_minus_Ca_minus_Gq_slash_PLCb_minus_Ca_minus_Gq_cplx
type: KineticLaw

406917
kinetic law: 430828
product: 430815
reactant: 430802
reactant: 430789
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

407937
kinetic law: 433322
product: 433310
product: 433298
reactant: 433285
fast: false
reversible: false
type: Reaction

401797
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

569130
units: 424878
value: 1.8E-13
type: LocalParameter

425255
stoichiometry: 1.0
species: 400757
type: SpeciesReference

426448
local parameters: 568898
local parameters: 568895
notes: kf*Ras_slash_GEF_star_-kb*Ras_slash_inact_minus_GEF
type: KineticLaw

431138
stoichiometry: 1.0
species: 401797
type: SpeciesReference

432996
stoichiometry: 1.0
species: 402817
type: SpeciesReference

432489
local parameters: 569241
local parameters: 569238
notes: kcat*PLC_g_slash_Ca_dot_PLC_g*PIP2/(Km+PIP2)
type: KineticLaw

569288
units: 424878
value: 2.04E-15
type: LocalParameter

430654
stoichiometry: 1.0
species: 401517
type: SpeciesReference

428294
stoichiometry: 1.0
species: 403617
type: SpeciesReference

431535
stoichiometry: 1.0
species: 401977
type: SpeciesReference

569135
units: 424962
value: 2.925045E-15
type: LocalParameter

433056
stoichiometry: 1.0
species: 402797
type: SpeciesReference

569062
units: 424878
value: 0.0
type: LocalParameter

400877
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

405077
kinetic law: 426485
product: 426473
reactant: 426460
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

426242
stoichiometry: 1.0
species: 401297
type: SpeciesReference

430254
stoichiometry: 1.0
species: 401537
type: SpeciesReference

569338
units: 424878
value: 3.0E-16
type: LocalParameter

431680
stoichiometry: 1.0
species: 402037
type: SpeciesReference

426922
stoichiometry: 1.0
species: 402517
type: SpeciesReference

569123
units: 424962
value: 2.250045E-14
type: LocalParameter

569289
units: 424878
value: 5.1E-16
type: LocalParameter

569063
units: 424962
value: 1.08E-12
type: LocalParameter

432693
local parameters: 569252
local parameters: 569251
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

426656
local parameters: 568918
local parameters: 568915
notes: kf*EGFR_slash_EGFR*EGFR_slash_EGF-kb*EGFR_slash_L_dot_EGFR
type: KineticLaw

400837
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

429758
stoichiometry: 1.0
species: 400977
type: SpeciesReference

433515
local parameters: 569283
notes: k3*CaM_po_Ca_pc_n_minus_CaNAB_slash_dephosph_inhib1_slash_dephosph_inhib1_cplx
type: KineticLaw

432729
stoichiometry: 1.0
species: 404317
type: SpeciesReference

568799
units: 424962
value: 1.799955E-18
type: LocalParameter

430085
local parameters: 569145
notes: k3*PLCbeta_slash_PLC_minus_Ca_slash_PLC_minus_Ca_slash_PLC_minus_Ca_cplx
type: KineticLaw

430714
stoichiometry: 1.0
species: 401677
type: SpeciesReference

569133
units: 424878
value: 1.5E-14
type: LocalParameter

428221
local parameters: 569050
local parameters: 569047
notes: kf*AC_slash_AC2*Gs_minus_alpha-kb*AC_slash_AC2_minus_Gs
type: KineticLaw

425145
stoichiometry: 1.0
species: 400578
type: SpeciesReference

428608
local parameters: 569086
local parameters: 569083
notes: kf*PKM_slash_PKM_synthesis-kb*PKM_slash_PKM_activator
type: KineticLaw

401617
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

403657
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.015
initial amount: NaN
in compartment: 400538
type: Species

428862
stoichiometry: 1.0
species: 400678
type: SpeciesReference

432260
stoichiometry: 1.0
species: 402297
type: SpeciesReference

569174
units: 424962
value: 1.41426E-14
type: LocalParameter

429104
local parameters: 569106
notes: k3*PKC_minus_active_slash_PKC_minus_phosph_minus_ng_minus_CaM_slash_PKC_minus_phosph_minus_ng_minus_CaM_cplx
type: KineticLaw

434024
stoichiometry: 1.0
species: 403557
type: SpeciesReference

432320
stoichiometry: 1.0
species: 402297
type: SpeciesReference

569335
units: 424962
value: 3.75003E-17
type: LocalParameter

569121
units: 424878
value: 5.4E-14
type: LocalParameter

426339
stoichiometry: 1.0
species: 401977
type: SpeciesReference

429250
local parameters: 569114
local parameters: 569111
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

403617
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

403337
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

428379
stoichiometry: 1.0
species: 402217
type: SpeciesReference

406737
kinetic law: 430388
product: 430376
product: 430363
reactant: 430351
fast: false
reversible: false
type: Reaction

425581
stoichiometry: 1.0
species: 401097
type: SpeciesReference

426097
stoichiometry: 1.0
species: 401357
type: SpeciesReference

433479
stoichiometry: 1.0
species: 403057
type: SpeciesReference

407457
kinetic law: 432140
product: 432127
product: 432115
reactant: 432103
fast: false
reversible: false
type: Reaction

569228
units: 424962
value: 2.97E-16
type: LocalParameter

402637
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

430351
stoichiometry: 1.0
species: 401557
type: SpeciesReference

408157
kinetic law: 433854
product: 433842
reactant: 433830
reactant: 433818
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

401537
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

427445
stoichiometry: 1.0
species: 403137
type: SpeciesReference

569139
units: 424878
value: 1.5E-14
type: LocalParameter

406117
kinetic law: 428850
product: 428838
reactant: 428825
reactant: 428813
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

569128
units: 424962
value: 4.499955E-14
type: LocalParameter

425939
stoichiometry: 1.0
species: 401277
type: SpeciesReference

404817
kinetic law: 425877
product: 425865
reactant: 425853
reactant: 425840
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

569229
units: 424878
value: 1.2E-16
type: LocalParameter

433914
stoichiometry: 1.0
species: 404237
type: SpeciesReference

569127
units: 424878
value: 9.0E-14
type: LocalParameter

569285
units: 424962
value: 5.13E-16
type: LocalParameter

425606
local parameters: 568826
local parameters: 568823
notes: kf*Ca*PLCbeta_slash_PLC-kb*PLCbeta_slash_PLC_minus_Ca
type: KineticLaw

404177
constant: true
boundary condition: true
has only substance units: false
initial concentration: 10.0
initial amount: NaN
in compartment: 400538
type: Species

431027
local parameters: 569183
local parameters: 569182
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

432779
stoichiometry: 1.0
species: 402757
type: SpeciesReference

568962
units: 424878
value: 0.0
type: LocalParameter

431921
stoichiometry: 1.0
species: 402077
type: SpeciesReference

425533
stoichiometry: 1.0
species: 400977
type: SpeciesReference

406497
kinetic law: 429783
product: 429770
product: 429758
reactant: 429746
fast: false
reversible: false
type: Reaction

432164
stoichiometry: 1.0
species: 402237
type: SpeciesReference

431644
stoichiometry: 1.0
species: 401937
type: SpeciesReference

429188
stoichiometry: 1.0
species: 404297
type: SpeciesReference

408237
kinetic law: 434048
modifier: 434036
product: 434024
reactant: 434012
fast: false
reversible: false
type: Reaction

569179
units: 424962
value: 4.28571E-15
type: LocalParameter

432912
stoichiometry: 1.0
species: 402637
type: SpeciesReference

569282
units: 424878
value: 2.04E-15
type: LocalParameter

434532
local parameters: 569333
notes: k3*AC_slash_CaM_dot_PDE1_slash_CaM_dot_PDE1_slash_CaM_dot_PDE1_cplx
type: KineticLaw

568963
units: 424914
value: 1.08000135E-13
type: LocalParameter

406417
kinetic law: 429589
product: 429576
product: 429564
reactant: 429552
fast: false
reversible: false
type: Reaction

406537
kinetic law: 429879
product: 429867
product: 429855
reactant: 429843
fast: false
reversible: false
type: Reaction

569126
units: 424878
value: 3.6E-13
type: LocalParameter

427372
local parameters: 568978
local parameters: 568975
notes: kf*CaM_slash_neurogranin*CaM_slash_CaM-kb*CaM_slash_neurogranin_minus_CaM
type: KineticLaw

428039
local parameters: 569034
local parameters: 569031
notes: kf*PKA_slash_R2C_minus_cAMP4-kb*PKA_minus_active*PKA_slash_R2_minus_cAMP4
type: KineticLaw

569226
units: 424878
value: 5.4E-14
type: LocalParameter

404757
kinetic law: 425728
product: 425715
reactant: 425703
reactant: 425691
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

427177
local parameters: 568962
local parameters: 568959
notes: kf*CaMKII_slash_CaMKII-kb*CaMKII_slash_CaMKII_minus_thr286
type: KineticLaw

569178
units: 424878
value: 4.5E-16
type: LocalParameter

425304
stoichiometry: 1.0
species: 404097
type: SpeciesReference

569283
units: 424878
value: 5.1E-16
type: LocalParameter

432839
local parameters: 569256
notes: k3*CaMKII_slash_tot_autonomous_CaMKII_slash_auton_305_slash_auton_305_cplx
type: KineticLaw

405937
kinetic law: 428451
product: 428439
reactant: 428427
reactant: 428415
notes: 18 May 2003. This reaction is here to provide basal activity for MAPK as well as the potential for direct EGF stimulus without PKC activation. Based on model from FB/fb28c.g: the model used for MKP-1 turnover. The rates there were constrained by basal activity values.
fast: false
reversible: true
type: Reaction

406457
kinetic law: 429686
product: 429674
product: 429662
reactant: 429650
fast: false
reversible: false
type: Reaction

569227
units: 424878
value: 1.35E-14
type: LocalParameter

429419
stoichiometry: 1.0
species: 400857
type: SpeciesReference

569138
units: 424878
value: 6.0E-14
type: LocalParameter

400757
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.4
initial amount: NaN
in compartment: 400538
type: Species

432019
stoichiometry: 1.0
species: 403117
type: SpeciesReference

569339
units: 424878
value: 7.5E-17
type: LocalParameter

425473
local parameters: 568814
local parameters: 568811
notes: kf*AA-kb*PLA2_slash_APC
type: KineticLaw

433781
stoichiometry: 1.0
species: 403157
type: SpeciesReference

569177
units: 424878
value: 1.8E-15
type: LocalParameter

429795
stoichiometry: 1.0
species: 401417
type: SpeciesReference

404597
kinetic law: 425389
product: 425377
reactant: 425364
reactant: 425352
fast: false
reversible: true
type: Reaction

405217
kinetic law: 426778
product: 426765
reactant: 426753
reactant: 426741
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

430868
stoichiometry: 1.0
species: 401657
type: SpeciesReference

407777
kinetic law: 432936
product: 432924
product: 432912
reactant: 432900
fast: false
reversible: false
type: Reaction

569119
units: 424962
value: 1.35E-14
type: LocalParameter

568966
units: 424878
value: 1.08E-13
type: LocalParameter

569341
units: 424878
value: 1.2E-15
type: LocalParameter

425975
local parameters: 568858
local parameters: 568855
notes: kf*Gq_slash_G_minus_GDP-kb*G_star_GTP*BetaGamma
type: KineticLaw

424902
exponent: -1.0
scale: 0
multipler: 1.0
kind: SECOND
type: SBMLUnit

569281
units: 424962
value: 5.13E-16
type: LocalParameter

429674
stoichiometry: 1.0
species: 400937
type: SpeciesReference

569236
units: 424878
value: 3.0E-16
type: LocalParameter

568926
units: 424878
value: 4.95E-19
type: LocalParameter

434253
stoichiometry: 1.0
species: 403557
type: SpeciesReference

405537
kinetic law: 427505
product: 427493
product: 427481
reactant: 427469
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

405257
kinetic law: 426862
product: 426850
reactant: 426838
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

431812
stoichiometry: 1.0
species: 402117
type: SpeciesReference

569342
units: 424878
value: 3.0E-16
type: LocalParameter

434713
stoichiometry: 1.0
species: 404017
type: SpeciesReference

425642
local parameters: 568830
local parameters: 568827
notes: kf*IP3-kb*PLCbeta_slash_Inositol
type: KineticLaw

430930
local parameters: 569180
local parameters: 569179
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

428149
stoichiometry: 1.0
species: 403617
type: SpeciesReference

569280
units: 424878
value: 1.005E-15
type: LocalParameter

425071
local parameters: 568786
local parameters: 568785
notes: kf*PKC_slash_PKC_minus_cytosolic*Ca-kb*PKC_slash_PKC_minus_Ca
type: KineticLaw

569235
units: 424878
value: 1.2E-15
type: LocalParameter

408457
kinetic law: 434580
product: 434568
reactant: 434556
reactant: 434544
fast: false
reversible: true
type: Reaction

429710
stoichiometry: 1.0
species: 400997
type: SpeciesReference

432803
stoichiometry: 1.0
species: 402757
type: SpeciesReference

568927
units: 424962
value: 7.499655E-16
type: LocalParameter

402317
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

569117
units: 424878
value: 6.624E-14
type: LocalParameter

429032
stoichiometry: 1.0
species: 400717
type: SpeciesReference

430570
stoichiometry: 1.0
species: 401597
type: SpeciesReference

433684
stoichiometry: 1.0
species: 403097
type: SpeciesReference

408517
kinetic law: 434725
product: 434713
product: 434701
reactant: 434689
fast: false
reversible: false
type: Reaction

429310
stoichiometry: 1.0
species: 404077
type: SpeciesReference

434181
stoichiometry: 1.0
species: 403757
type: SpeciesReference

433745
stoichiometry: 1.0
species: 403217
type: SpeciesReference

429528
stoichiometry: 1.0
species: 400917
type: SpeciesReference

569234
units: 424962
value: 1.799955E-15
type: LocalParameter

569129
units: 424878
value: 7.2E-13
type: LocalParameter

432609
stoichiometry: 1.0
species: 402717
type: SpeciesReference

432948
stoichiometry: 1.0
species: 402637
type: SpeciesReference

569118
units: 424878
value: 1.656E-14
type: LocalParameter

569340
units: 424962
value: 2.99997E-16
type: LocalParameter

430109
stoichiometry: 1.0
species: 401157
type: SpeciesReference

568967
units: 424962
value: 5.4E-15
type: LocalParameter

427069
stoichiometry: 1.0
species: 402597
type: SpeciesReference

408497
kinetic law: 434677
product: 434664
reactant: 434652
reactant: 434640
fast: false
reversible: true
type: Reaction

434677
local parameters: 569341
local parameters: 569340
notes: k1*PKM_slash_PKM_activator*PKM_slash_Ca_dot_detector_complex-k2*PKM_slash_Ca_dot_detector_complex_slash_kenz_slash_kenz_cplx
type: KineticLaw

431764
stoichiometry: 1.0
species: 401997
type: SpeciesReference

405297
kinetic law: 426958
product: 426946
reactant: 426934
reactant: 426922
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 will 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

569171
units: 424878
value: 1.8E-15
type: LocalParameter

430606
stoichiometry: 1.0
species: 401597
type: SpeciesReference

431426
stoichiometry: 1.0
species: 401857
type: SpeciesReference

426958
local parameters: 568946
local parameters: 568943
notes: kf*PLC_g_slash_PLC_g*Ca-kb*PLC_g_slash_Ca_dot_PLC_g
type: KineticLaw

569026
units: 424878
value: 4.875E-14
type: LocalParameter

569233
units: 424878
value: 3.0E-16
type: LocalParameter

427735
stoichiometry: 1.0
species: 403357
type: SpeciesReference

406677
kinetic law: 430242
product: 430230
reactant: 430218
reactant: 430206
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

404657
kinetic law: 425521
product: 425509
reactant: 425497
reactant: 425485
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

403557
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

568898
units: 424878
value: 0.0
type: LocalParameter

406897
kinetic law: 430776
product: 430764
product: 430751
reactant: 430738
fast: false
reversible: false
type: Reaction

569067
units: 424962
value: 0.0
type: LocalParameter

427662
stoichiometry: 1.0
species: 402997
type: SpeciesReference

569172
units: 424878
value: 4.5E-16
type: LocalParameter

408097
kinetic law: 433708
product: 433696
product: 433684
reactant: 433671
fast: false
reversible: false
type: Reaction

425752
stoichiometry: 1.0
species: 401257
type: SpeciesReference

569232
units: 424878
value: 1.2E-15
type: LocalParameter

569027
units: 424878
value: 9.0E-14
type: LocalParameter

426498
stoichiometry: 1.0
species: 402017
type: SpeciesReference

426728
local parameters: 568926
local parameters: 568923
notes: kf*EGFR_slash_L_dot_EGFR-kb*EGFR_slash_Internal_L_dot_EGFR
type: KineticLaw

403997
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

400538
constant: true
size: 1.5E-15
spatial dimensions: 3.0
type: Compartment

568899
units: 424878
value: 1.5E-19
type: LocalParameter

432657
stoichiometry: 1.0
species: 402617
type: SpeciesReference

569066
units: 424878
value: 7.5E-15
type: LocalParameter

432597
local parameters: 569249
local parameters: 569246
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

429638
local parameters: 569129
local parameters: 569128
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

425243
local parameters: 568794
local parameters: 568793
notes: kf*PKC_slash_PKC_minus_cytosolic*DAG-kb*PKC_slash_PKC_minus_DAG
type: KineticLaw

430037
stoichiometry: 1.0
species: 401137
type: SpeciesReference

425691
stoichiometry: 1.0
species: 401237
type: SpeciesReference

569231
units: 424962
value: 4.499955E-15
type: LocalParameter

432224
stoichiometry: 1.0
species: 402237
type: SpeciesReference

426436
stoichiometry: 1.0
species: 401917
type: SpeciesReference

426388
stoichiometry: 1.0
species: 401917
type: SpeciesReference

403917
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.08
initial amount: NaN
in compartment: 400538
type: Species

568819
units: 424878
value: 2.55E-16
type: LocalParameter

426061
local parameters: 568866
local parameters: 568863
notes: kf*G_star_GTP-kb*G_star_GDP
type: KineticLaw

429395
local parameters: 569118
notes: k3*PLA2_slash_PIP2_minus_PLA2_star__slash_kenz_slash_kenz_cplx
type: KineticLaw

428656
local parameters: 569090
local parameters: 569087
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

569170
units: 424962
value: 1.41426E-14
type: LocalParameter

428257
stoichiometry: 1.0
species: 403677
type: SpeciesReference

426996
stoichiometry: 1.0
species: 402577
type: SpeciesReference

430182
stoichiometry: 1.0
species: 401157
type: SpeciesReference

404237
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: 400538
type: Species

403957
constant: false
boundary condition: false
has only substance units: false
initial concentration: 1.0
initial amount: NaN
in compartment: 400538
type: Species

569230
units: 424878
value: 3.0E-17
type: LocalParameter

425182
stoichiometry: 1.0
species: 400597
type: SpeciesReference

424986
exponent: -1.0
scale: -6
multipler: 1.0
kind: MOLE
type: SBMLUnit

433322
local parameters: 569277
notes: k3*PP1_minus_active_slash_Deph_thr286b_slash_Deph_thr286b_cplx
type: KineticLaw

568818
units: 424878
value: 1.5E-16
type: LocalParameter

430304
stoichiometry: 1.0
species: 401497
type: SpeciesReference

407037
kinetic law: 431126
product: 431114
reactant: 431102
reactant: 431090
notes: See parent PPhosphatase2A for parms
fast: false
reversible: true
type: Reaction

427553
local parameters: 568994
local parameters: 568991
notes: kf*Ca^2*PP2B_slash_CaNAB_minus_Ca2-kb*CaNAB_minus_Ca4
type: KineticLaw

401997
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.5
initial amount: NaN
in compartment: 400538
type: Species

427626
stoichiometry: 1.0
species: 403017
type: SpeciesReference

432549
local parameters: 569245
local parameters: 569242
notes: kcat*PLC_g_slash_Ca_dot_PLC_g_star_*PIP2/(Km+PIP2)
type: KineticLaw

430978
local parameters: 569181
notes: k3*MKP_minus_1_slash_MKP1_minus_tyr_minus_deph_slash_MKP1_minus_tyr_minus_deph_cplx
type: KineticLaw

569022
units: 424878
value: 1.65E-13
type: LocalParameter

568855
units: 424878
value: 1.5E-19
type: LocalParameter

433152
stoichiometry: 1.0
species: 402797
type: SpeciesReference

407717
kinetic law: 432791
product: 432779
reactant: 432766
reactant: 432754
notes: See Hanson and Schulman again, for afterburst rates of phosph.
fast: false
reversible: true
type: Reaction

433963
stoichiometry: 1.0
species: 404237
type: SpeciesReference

568894
units: 424878
value: 1.5E-15
type: LocalParameter

405437
kinetic law: 427274
product: 427262
reactant: 427250
reactant: 427238
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

428704
local parameters: 569091
notes: k3*PKC_minus_active_slash_PKC_minus_act_minus_raf_slash_PKC_minus_act_minus_raf_cplx
type: KineticLaw

405037
kinetic law: 426412
product: 426400
reactant: 426388
reactant: 426375
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

402997
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

402177
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

433806
local parameters: 569295
notes: k3*PP2A_slash_PP2A_minus_dephosph_minus_PP1_minus_I_star__slash_PP2A_minus_dephosph_minus_PP1_minus_I_star__cplx
type: KineticLaw

433008
stoichiometry: 1.0
species: 402617
type: SpeciesReference

400937
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

401957
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

569023
units: 424962
value: 1.1249955E-13
type: LocalParameter

428475
stoichiometry: 1.0
species: 403917
type: SpeciesReference

568854
units: 424878
value: 1.5E-14
type: LocalParameter

568895
units: 424878
value: 1.5E-15
type: LocalParameter

434423
stoichiometry: 1.0
species: 403817
type: SpeciesReference

430534
local parameters: 569165
local parameters: 569162
notes: k1*MAPK_slash_MAPKK*MAPK_slash_Raf_minus_GTP_minus_Ras-k2*MAPK_slash_Raf_minus_GTP_minus_Ras_slash_Raf_minus_GTP_minus_Ras_dot_1_slash_Raf_minus_GTP_minus_Ras_dot_1_cplx
type: KineticLaw

568815
units: 424962
value: 9.000045E-15
type: LocalParameter

401257
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

432888
local parameters: 569261
local parameters: 569258
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

425352
stoichiometry: 1.0
species: 404097
type: SpeciesReference

405797
kinetic law: 428137
product: 428125
reactant: 428112
reactant: 428100
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

568814
units: 424878
value: 0.0
type: LocalParameter

428500
stoichiometry: 1.0
species: 403957
type: SpeciesReference

433213
stoichiometry: 1.0
species: 402797
type: SpeciesReference

425425
stoichiometry: 1.0
species: 400897
type: SpeciesReference

430291
local parameters: 569154
notes: k3*MAPK_slash_MAPKK_star__slash_MAPKKtyr_slash_MAPKKtyr_cplx
type: KineticLaw

432332
local parameters: 569233
notes: k3*EGFR_slash_L_dot_EGFR_slash_phosph_PLC_g_slash_phosph_PLC_g_cplx
type: KineticLaw

431704
local parameters: 569210
local parameters: 569209
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

429358
stoichiometry: 1.0
species: 400837
type: SpeciesReference

401217
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

405857
kinetic law: 428269
product: 428257
reactant: 428245
reactant: 428233
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

428100
stoichiometry: 1.0
species: 402217
type: SpeciesReference

406157
kinetic law: 428947
product: 428935
reactant: 428923
reactant: 428911
notes: Rates from Huang et al ABB 305:2 570-580 1993
fast: false
reversible: true
type: Reaction

431572
stoichiometry: 1.0
species: 401997
type: SpeciesReference

425035
stoichiometry: 1.0
species: 400618
type: SpeciesReference

568851
units: 424962
value: 2.520045E-14
type: LocalParameter

404857
kinetic law: 425975
product: 425963
product: 425951
reactant: 425939
notes: kf = kg1 = 0.01/sec, kb = 0. This is the basal exchange of GTP for GDP.
fast: false
reversible: true
type: Reaction

568890
units: 424878
value: 7.5E-16
type: LocalParameter

428439
stoichiometry: 1.0
species: 401597
type: SpeciesReference

400717
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

402817
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

407497
kinetic law: 432236
product: 432224
product: 432212
reactant: 432200
fast: false
reversible: false
type: Reaction

403137
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

401577
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

402017
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

429468
stoichiometry: 1.0
species: 400657
type: SpeciesReference

568850
units: 424878
value: 1.5E-15
type: LocalParameter

403177
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.12
initial amount: NaN
in compartment: 400538
type: Species

568891
units: 424962
value: 9.000045E-15
type: LocalParameter

403497
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

433116
stoichiometry: 1.0
species: 402797
type: SpeciesReference

568922
units: 424878
value: 0.0
type: LocalParameter

426548
stoichiometry: 1.0
species: 402217
type: SpeciesReference

434460
stoichiometry: 1.0
species: 403857
type: SpeciesReference

425728
local parameters: 568838
local parameters: 568835
notes: kf*G_star_GTP*PLCbeta_slash_PLC_minus_Ca-kb*PLCbeta_slash_PLC_minus_Ca_minus_Gq
type: KineticLaw

431234
stoichiometry: 1.0
species: 401817
type: SpeciesReference

429928
local parameters: 569141
local parameters: 569140
notes: k1*Sos_slash_Sos*MAPK_star_-k2*MAPK_star__slash_phosph_Sos_slash_phosph_Sos_cplx
type: KineticLaw

402357
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.5
initial amount: NaN
in compartment: 400538
type: Species

433793
stoichiometry: 1.0
species: 403177
type: SpeciesReference

431970
stoichiometry: 1.0
species: 402137
type: SpeciesReference

408277
kinetic law: 434145
modifier: 434133
product: 434121
reactant: 434108
fast: false
reversible: false
type: Reaction

568811
units: 424878
value: 6.0E-16
type: LocalParameter

568923
units: 424878
value: 3.0E-18
type: LocalParameter

429867
stoichiometry: 1.0
species: 400997
type: SpeciesReference

431065
stoichiometry: 1.0
species: 401717
type: SpeciesReference

427274
local parameters: 568970
local parameters: 568967
notes: kf*CaM_minus_TR2_minus_Ca2*Ca-kb*CaM_minus_Ca3
type: KineticLaw

430218
stoichiometry: 1.0
species: 401517
type: SpeciesReference

434108
stoichiometry: 1.0
species: 404237
type: SpeciesReference

407417
kinetic law: 432043
product: 432031
product: 432019
reactant: 432007
fast: false
reversible: false
type: Reaction

568810
units: 424878
value: 6.0E-15
type: LocalParameter

402677
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

428185
stoichiometry: 1.0
species: 403657
type: SpeciesReference

433854
local parameters: 569297
local parameters: 569296
notes: k1*PP1_slash_I1_star_*CaNAB_minus_Ca4-k2*CaNAB_minus_Ca4_slash_dephosph_inhib1_noCaM_slash_dephosph_inhib1_noCaM_cplx
type: KineticLaw

408117
kinetic law: 433757
product: 433745
reactant: 433733
reactant: 433720
notes: k1 changed from 3.3e-6 to 6.6e-6
fast: false
reversible: true
type: Reaction

400797
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

429807
stoichiometry: 1.0
species: 400997
type: SpeciesReference

428947
local parameters: 569102
local parameters: 569099
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

429564
stoichiometry: 1.0
species: 400657
type: SpeciesReference

401717
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.02
initial amount: NaN
in compartment: 400538
type: Species

407537
kinetic law: 432332
product: 432320
product: 432308
reactant: 432296
fast: false
reversible: false
type: Reaction

404277
constant: true
boundary condition: true
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

430815
stoichiometry: 1.0
species: 401697
type: SpeciesReference

403757
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

428899
local parameters: 569097
notes: k3*PKC_minus_active_slash_PKC_minus_act_minus_GEF_slash_PKC_minus_act_minus_GEF_cplx
type: KineticLaw

402377
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

426012
stoichiometry: 1.0
species: 401277
type: SpeciesReference

408297
kinetic law: 434193
product: 434181
reactant: 434169
reactant: 434157
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

403797
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

427845
local parameters: 569018
local parameters: 569015
notes: kf*PKA_slash_R2C2_minus_cAMP*cAMP-kb*PKA_slash_R2C2_minus_cAMP2
type: KineticLaw

401757
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

434361
stoichiometry: 1.0
species: 403817
type: SpeciesReference

431474
stoichiometry: 1.0
species: 401997
type: SpeciesReference

434217
stoichiometry: 1.0
species: 403697
type: SpeciesReference

433249
stoichiometry: 1.0
species: 402797
type: SpeciesReference

432115
stoichiometry: 1.0
species: 403777
type: SpeciesReference

403057
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

403717
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

425268
stoichiometry: 1.0
species: 403917
type: SpeciesReference

427955
stoichiometry: 1.0
species: 403457
type: SpeciesReference

428087
local parameters: 569038
local parameters: 569035
notes: kf*PKA_minus_active*PKA_slash_PKA_minus_inhibitor-kb*PKA_slash_inhibited_minus_PKA
type: KineticLaw

406037
kinetic law: 428656
product: 428644
reactant: 428632
reactant: 428620
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

401137
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

403017
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

427918
stoichiometry: 1.0
species: 403437
type: SpeciesReference

426898
stoichiometry: 1.0
species: 402457
type: SpeciesReference

432043
local parameters: 569222
notes: k3*PKA_minus_active_slash_PKA_minus_phosph_minus_I1_slash_PKA_minus_phosph_minus_I1_cplx
type: KineticLaw

428740
stoichiometry: 1.0
species: 400677
type: SpeciesReference

429492
local parameters: 569121
notes: k3*PLA2_slash_PIP2_minus_Ca_minus_PLA2_star__slash_kenz_slash_kenz_cplx
type: KineticLaw

405617
kinetic law: 427699
product: 427686
reactant: 427674
reactant: 427662
fast: false
reversible: true
type: Reaction

403117
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.001
initial amount: NaN
in compartment: 400538
type: Species

569140
units: 424962
value: 2.925045E-14
type: LocalParameter

400658
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

406637
kinetic law: 430133
product: 430121
reactant: 430109
reactant: 430097
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

408037
kinetic law: 433563
product: 433551
reactant: 433539
reactant: 433527
fast: false
reversible: true
type: Reaction

429965
stoichiometry: 1.0
species: 400997
type: SpeciesReference

427323
local parameters: 568974
local parameters: 568971
notes: kf*CaM_minus_Ca3*Ca-kb*CaM_minus_Ca4
type: KineticLaw

426814
stoichiometry: 1.0
species: 402417
type: SpeciesReference

430474
stoichiometry: 1.0
species: 402797
type: SpeciesReference

425865
stoichiometry: 1.0
species: 401157
type: SpeciesReference

406397
kinetic law: 429540
product: 429528
reactant: 429516
reactant: 429504
notes: 10 X raise oct 22 12 X raise oct 24 + conversion to k2 =4 * k3
fast: false
reversible: true
type: Reaction

401477
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

400657
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

568786
units: 424878
value: 7.5E-16
type: LocalParameter

569141
units: 424878
value: 6.0E-14
type: LocalParameter

434325
stoichiometry: 1.0
species: 403777
type: SpeciesReference

428403
local parameters: 569066
local parameters: 569063
notes: kf*AC_slash_PDE1*CaM_minus_Ca4-kb*AC_slash_CaM_dot_PDE1
type: KineticLaw

403857
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

432380
local parameters: 569235
local parameters: 569234
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

426608
local parameters: 568914
local parameters: 568911
notes: kf*Ras_slash_inact_minus_GEF_star_-kb*Ras_slash_inact_minus_GEF
type: KineticLaw

568785
units: 424962
value: 9.000045E-16
type: LocalParameter

569142
units: 424878
value: 1.5E-14
type: LocalParameter

428003
stoichiometry: 1.0
species: 403477
type: SpeciesReference

407317
kinetic law: 431800
product: 431788
reactant: 431776
reactant: 431764
notes: Kinetics same as GEF-bg_act-ras
fast: false
reversible: true
type: Reaction

430133
local parameters: 569150
local parameters: 569147
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

433635
stoichiometry: 1.0
species: 403177
type: SpeciesReference

433575
stoichiometry: 1.0
species: 403077
type: SpeciesReference

429152
local parameters: 569108
local parameters: 569107
notes: k1*AC_slash_AC2*PKC_minus_active-k2*PKC_minus_active_slash_phosph_minus_AC2_slash_phosph_minus_AC2_cplx
type: KineticLaw

569143
units: 424962
value: 3.78E-15
type: LocalParameter

404697
kinetic law: 425606
product: 425594
reactant: 425581
reactant: 425569
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

406857
kinetic law: 430678
product: 430666
product: 430654
reactant: 430642
fast: false
reversible: false
type: Reaction

406357
kinetic law: 429443
product: 429431
reactant: 429419
reactant: 429407
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

432573
stoichiometry: 1.0
species: 404317
type: SpeciesReference

407737
kinetic law: 432839
product: 432827
product: 432815
reactant: 432803
fast: false
reversible: false
type: Reaction

433285
stoichiometry: 1.0
species: 402897
type: SpeciesReference

426122
stoichiometry: 1.0
species: 404117
type: SpeciesReference

430751
stoichiometry: 1.0
species: 401577
type: SpeciesReference

429226
stoichiometry: 1.0
species: 400777
type: SpeciesReference

431872
stoichiometry: 1.0
species: 402137
type: SpeciesReference

569144
units: 424878
value: 6.0E-14
type: LocalParameter

428596
stoichiometry: 1.0
species: 404057
type: SpeciesReference

430436
local parameters: 569159
local parameters: 569158
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

406317
kinetic law: 429346
product: 429334
reactant: 429322
reactant: 429310
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

403397
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

424866
exponent: 1.0
scale: -6
multipler: 1.0
kind: MOLE
type: SBMLUnit

426753
stoichiometry: 1.0
species: 402377
type: SpeciesReference

402777
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

425157
local parameters: 568790
local parameters: 568789
notes: kf*PKC_slash_PKC_minus_Ca-kb*PKC_slash_PKC_minus_Ca_minus_memb_star_
type: KineticLaw

429892
stoichiometry: 1.0
species: 402497
type: SpeciesReference

405957
kinetic law: 428488
product: 428475
reactant: 428463
fast: false
reversible: true
type: Reaction

425594
stoichiometry: 1.0
species: 401117
type: SpeciesReference

569218
units: 424878
value: 1.35E-14
type: LocalParameter

430097
stoichiometry: 1.0
species: 404177
type: SpeciesReference

569324
units: 424878
value: 1.5E-14
type: LocalParameter

569298
units: 424878
value: 5.1E-17
type: LocalParameter

430702
stoichiometry: 1.0
species: 401657
type: SpeciesReference

569145
units: 424878
value: 1.5E-14
type: LocalParameter

432272
stoichiometry: 1.0
species: 402317
type: SpeciesReference

429116
stoichiometry: 1.0
species: 403657
type: SpeciesReference

568971
units: 424962
value: 6.975045E-16
type: LocalParameter

569186
units: 424878
value: 3.6E-14
type: LocalParameter

428850
local parameters: 569096
local parameters: 569095
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

569219
units: 424962
value: 9.000045E-15
type: LocalParameter

401817
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

569323
units: 424878
value: 6.0E-14
type: LocalParameter

428367
stoichiometry: 1.0
species: 403817
type: SpeciesReference

405997
kinetic law: 428572
product: 428560
reactant: 428548
notes: Time-course of 2 hours.
fast: false
reversible: true
type: Reaction

429262
stoichiometry: 1.0
species: 400797
type: SpeciesReference

569185
units: 424962
value: 2.87415E-15
type: LocalParameter

568789
units: 424878
value: 1.90575E-15
type: LocalParameter

433467
local parameters: 569282
local parameters: 569281
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

405897
kinetic law: 428355
product: 428342
reactant: 428330
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

569074
units: 424878
value: 1.5E-13
type: LocalParameter

430642
stoichiometry: 1.0
species: 401637
type: SpeciesReference

431547
stoichiometry: 1.0
species: 401877
type: SpeciesReference

401897
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

569147
units: 424962
value: 7.199955E-14
type: LocalParameter

433044
stoichiometry: 1.0
species: 402697
type: SpeciesReference

431692
stoichiometry: 1.0
species: 402057
type: SpeciesReference

430242
local parameters: 569153
local parameters: 569152
notes: k1*MAPK_slash_MAPK*MAPK_slash_MAPKK_star_-k2*MAPK_slash_MAPKK_star__slash_MAPKKtyr_slash_MAPKKtyr_cplx
type: KineticLaw

403237
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

569326
units: 424878
value: 1.2E-13
type: LocalParameter

408397
kinetic law: 434436
product: 434423
product: 434410
reactant: 434398
fast: false
reversible: false
type: Reaction

568788
units: 424878
value: 1.29522E-14
type: LocalParameter

426230
stoichiometry: 1.0
species: 401277
type: SpeciesReference

433395
stoichiometry: 1.0
species: 402977
type: SpeciesReference

569075
units: 424914
value: 1.500039E-16
type: LocalParameter

400977
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

430327
stoichiometry: 1.0
species: 401557
type: SpeciesReference

401317
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

432681
stoichiometry: 1.0
species: 402737
type: SpeciesReference

426644
stoichiometry: 1.0
species: 402297
type: SpeciesReference

407237
kinetic law: 431608
product: 431596
reactant: 431584
reactant: 431572
notes: Kinetics same as GEF-bg-act-ras
fast: false
reversible: true
type: Reaction

408357
kinetic law: 434337
product: 434325
product: 434313
reactant: 434301
fast: false
reversible: false
type: Reaction

426910
local parameters: 568942
local parameters: 568939
notes: kf*Sos_slash_Grb2*Sos_slash_Sos-kb*Sos_slash_Sos_dot_Grb2
type: KineticLaw

402857
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

569111
units: 424962
value: 2.025E-15
type: LocalParameter

569325
units: 424962
value: 7.56E-15
type: LocalParameter

429746
stoichiometry: 1.0
species: 401017
type: SpeciesReference

568970
units: 424878
value: 1.5E-14
type: LocalParameter

433527
stoichiometry: 1.0
species: 403137
type: SpeciesReference

568787
units: 424962
value: 1.1999745E-17
type: LocalParameter

569187
units: 424878
value: 9.0E-15
type: LocalParameter

568975
units: 424962
value: 4.499955E-16
type: LocalParameter

569114
units: 424878
value: 3.24E-14
type: LocalParameter

432900
stoichiometry: 1.0
species: 402777
type: SpeciesReference

569294
units: 424878
value: 3.75E-14
type: LocalParameter

434544
stoichiometry: 1.0
species: 404257
type: SpeciesReference

408437
kinetic law: 434532
product: 434520
product: 434508
reactant: 434496
fast: false
reversible: false
type: Reaction

432960
stoichiometry: 1.0
species: 402797
type: SpeciesReference

401657
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

569214
units: 424878
value: 3.0E-17
type: LocalParameter

407297
kinetic law: 431752
product: 431740
product: 431728
reactant: 431716
fast: false
reversible: false
type: Reaction

427165
stoichiometry: 1.0
species: 402677
type: SpeciesReference

428838
stoichiometry: 1.0
species: 400678
type: SpeciesReference

402517
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.82
initial amount: NaN
in compartment: 400538
type: Species

429008
stoichiometry: 1.0
species: 402937
type: SpeciesReference

569328
units: 424962
value: 3.149955E-16
type: LocalParameter

427021
stoichiometry: 1.0
species: 402577
type: SpeciesReference

428789
stoichiometry: 1.0
species: 404297
type: SpeciesReference

401697
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

569295
units: 424878
value: 9.0E-15
type: LocalParameter

407257
kinetic law: 431656
product: 431644
product: 431632
reactant: 431620
fast: false
reversible: false
type: Reaction

434145
local parameters: 569319
local parameters: 569316
notes: kcat*AC_slash_AC2_star__minus_Gs*AC_slash_ATP/(Km+AC_slash_ATP)
type: KineticLaw

569215
units: 424962
value: 9.000045E-15
type: LocalParameter

429783
local parameters: 569133
notes: k3*MAPK_star__slash_MAPK_star__slash_MAPK_star__cplx
type: KineticLaw

569189
units: 424962
value: 2.87415E-15
type: LocalParameter

569327
units: 424878
value: 3.0E-14
type: LocalParameter

432007
stoichiometry: 1.0
species: 402177
type: SpeciesReference

425485
stoichiometry: 1.0
species: 400977
type: SpeciesReference

400917
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

405557
kinetic law: 427553
product: 427541
reactant: 427529
reactant: 427517
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

569296
units: 424962
value: 5.13E-17
type: LocalParameter

569116
units: 424962
value: 4.140045E-15
type: LocalParameter

427433
stoichiometry: 1.0
species: 402797
type: SpeciesReference

569216
units: 424878
value: 5.4E-14
type: LocalParameter

402557
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

569070
units: 424878
value: 0.0
type: LocalParameter

434628
local parameters: 569339
notes: k3*PKM_slash_PKM_synthesis_slash_kenz_slash_kenz_cplx
type: KineticLaw

430363
stoichiometry: 1.0
species: 400997
type: SpeciesReference

425618
stoichiometry: 1.0
species: 401077
type: SpeciesReference

569115
units: 424878
value: 8.1E-15
type: LocalParameter

569297
units: 424878
value: 2.04E-16
type: LocalParameter

404477
kinetic law: 425121
product: 425108
reactant: 425096
reactant: 425083
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

425545
stoichiometry: 1.0
species: 400757
type: SpeciesReference

568974
units: 424878
value: 1.5E-14
type: LocalParameter

402597
constant: false
boundary condition: false
has only substance units: false
initial concentration: 70.0
initial amount: NaN
in compartment: 400538
type: Species

431039
stoichiometry: 1.0
species: 401757
type: SpeciesReference

433902
local parameters: 569298
notes: k3*CaNAB_minus_Ca4_slash_dephosph_inhib1_noCaM_slash_dephosph_inhib1_noCaM_cplx
type: KineticLaw

402117
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

569071
units: 424878
value: 1.5E-13
type: LocalParameter

429601
stoichiometry: 1.0
species: 404077
type: SpeciesReference

432428
local parameters: 569236
notes: k3*EGFR_slash_L_dot_EGFR_slash_phosph_Shc_slash_phosph_Shc_cplx
type: KineticLaw

432152
stoichiometry: 1.0
species: 401997
type: SpeciesReference

403457
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

431656
local parameters: 569208
notes: k3*Ras_slash_GEF_star__slash_GEF_star__minus_act_minus_ras_slash_GEF_star__minus_act_minus_ras_cplx
type: KineticLaw

431933
stoichiometry: 1.0
species: 402137
type: SpeciesReference

405477
kinetic law: 427372
product: 427359
reactant: 427347
reactant: 427335
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

405597
kinetic law: 427650
product: 427638
reactant: 427626
reactant: 427614
notes: Disabled. See notes for PP2B7.g
fast: false
reversible: true
type: Reaction

569329
units: 424878
value: 1.0005E-14
type: LocalParameter

433359
stoichiometry: 1.0
species: 403037
type: SpeciesReference

427809
stoichiometry: 1.0
species: 403397
type: SpeciesReference

400618
constant: false
boundary condition: false
has only substance units: false
initial concentration: 1.0
initial amount: NaN
in compartment: 400538
type: Species

568939
units: 424962
value: 3.75003E-17
type: LocalParameter

425083
stoichiometry: 1.0
species: 400638
type: SpeciesReference

434508
stoichiometry: 1.0
species: 403697
type: SpeciesReference

426460
stoichiometry: 1.0
species: 401977
type: SpeciesReference

569223
units: 424962
value: 9.000045E-15
type: LocalParameter

433696
stoichiometry: 1.0
species: 403177
type: SpeciesReference

569291
units: 424878
value: 3.75E-14
type: LocalParameter

430582
local parameters: 569166
notes: k3*MAPK_slash_Raf_minus_GTP_minus_Ras_slash_Raf_minus_GTP_minus_Ras_dot_1_slash_Raf_minus_GTP_minus_Ras_dot_1_cplx
type: KineticLaw

407197
kinetic law: 431511
product: 431499
reactant: 431486
reactant: 431474
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

432851
stoichiometry: 1.0
species: 402617
type: SpeciesReference

426279
stoichiometry: 1.0
species: 401337
type: SpeciesReference

569105
units: 424878
value: 2.1E-15
type: LocalParameter

429044
local parameters: 569105
local parameters: 569104
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

402217
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

407997
kinetic law: 433467
product: 433455
reactant: 433443
reactant: 433431
fast: false
reversible: true
type: Reaction

407877
kinetic law: 433176
product: 433164
reactant: 433152
reactant: 433140
fast: false
reversible: true
type: Reaction

569106
units: 424878
value: 5.25E-16
type: LocalParameter

434193
local parameters: 569323
local parameters: 569320
notes: k1*cAMP*AC_slash_cAMP_minus_PDE-k2*AC_slash_cAMP_minus_PDE_slash_PDE_slash_PDE_cplx
type: KineticLaw

569222
units: 424878
value: 1.35E-14
type: LocalParameter

433733
stoichiometry: 1.0
species: 403177
type: SpeciesReference

407157
kinetic law: 431414
product: 431402
reactant: 431390
reactant: 431378
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

569290
units: 424962
value: 5.94E-15
type: LocalParameter

431186
stoichiometry: 1.0
species: 401517
type: SpeciesReference

431752
local parameters: 569211
notes: k3*Ras_slash_GAP_slash_GAP_minus_inact_minus_ras_slash_GAP_minus_inact_minus_ras_cplx
type: KineticLaw

430789
stoichiometry: 1.0
species: 401577
type: SpeciesReference

568979
units: 424878
value: 7.5E-18
type: LocalParameter

406517
kinetic law: 429831
product: 429819
reactant: 429807
reactant: 429795
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

405337
kinetic law: 427045
product: 427033
reactant: 427021
fast: false
reversible: true
type: Reaction

427057
stoichiometry: 1.0
species: 402217
type: SpeciesReference

569107
units: 424962
value: 9.000045E-16
type: LocalParameter

427894
local parameters: 569022
local parameters: 569019
notes: kf*PKA_slash_R2C2_minus_cAMP2*cAMP-kb*PKA_slash_R2C2_minus_cAMP3
type: KineticLaw

425987
stoichiometry: 1.0
species: 401257
type: SpeciesReference

569293
units: 424962
value: 5.94E-15
type: LocalParameter

434664
stoichiometry: 1.0
species: 404037
type: SpeciesReference

429686
local parameters: 569130
notes: k3*PLA2_slash_PLA2_star__minus_Ca_slash_kenz_slash_kenz_cplx
type: KineticLaw

568978
units: 424878
value: 1.5E-15
type: LocalParameter

569108
units: 424878
value: 2.4E-14
type: LocalParameter

568938
units: 424878
value: 0.0
type: LocalParameter

407577
kinetic law: 432428
product: 432416
product: 432404
reactant: 432392
fast: false
reversible: false
type: Reaction

569180
units: 424878
value: 2.4E-14
type: LocalParameter

425509
stoichiometry: 1.0
species: 400937
type: SpeciesReference

434241
local parameters: 569324
notes: k3*AC_slash_cAMP_minus_PDE_slash_PDE_slash_PDE_cplx
type: KineticLaw

400578
constant: false
boundary condition: false
has only substance units: false
initial concentration: 1.38955555555556E-17
initial amount: NaN
in compartment: 400538
type: Species

427589
stoichiometry: 1.0
species: 403297
type: SpeciesReference

430855
stoichiometry: 1.0
species: 401517
type: SpeciesReference

569292
units: 424878
value: 9.0E-15
type: LocalParameter

434725
local parameters: 569342
notes: k3*PKM_slash_Ca_dot_detector_complex_slash_kenz_slash_kenz_cplx
type: KineticLaw

425654
stoichiometry: 1.0
species: 400638
type: SpeciesReference

431824
stoichiometry: 1.0
species: 401977
type: SpeciesReference

569330
units: 424878
value: 2.5005E-15
type: LocalParameter

431114
stoichiometry: 1.0
species: 401797
type: SpeciesReference

432236
local parameters: 569230
notes: k3*Shc_star__dot_Sos_dot_Grb2_slash_Sos_dot_Ras_GEF_slash_Sos_dot_Ras_GEF_cplx
type: KineticLaw

400697
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

404537
kinetic law: 425243
product: 425231
reactant: 425218
reactant: 425206
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

425231
stoichiometry: 1.0
species: 400617
type: SpeciesReference

569181
units: 424878
value: 6.0E-15
type: LocalParameter

427093
local parameters: 568954
local parameters: 568951
notes: kf*CaM_minus_Ca4*CaMKII_slash_CaMKII-kb*CaMKII_slash_CaMKII_minus_CaM
type: KineticLaw

430025
local parameters: 569144
local parameters: 569143
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

403357
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

569109
units: 424878
value: 6.0E-15
type: LocalParameter

569331
units: 424962
value: 1.89E-15
type: LocalParameter

402277
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.166666666666667
initial amount: NaN
in compartment: 400538
type: Species

428668
stoichiometry: 1.0
species: 400658
type: SpeciesReference

426424
stoichiometry: 1.0
species: 401937
type: SpeciesReference

406757
kinetic law: 430436
product: 430424
reactant: 430412
reactant: 430400
fast: false
reversible: true
type: Reaction

407837
kinetic law: 433080
product: 433068
reactant: 433056
reactant: 433044
notes: See Cohen et al
fast: false
reversible: true
type: Reaction

432742
local parameters: 569253
notes: k3*CaMKII_slash_tot_CaM_CaMKII_slash_CaM_act_286_slash_CaM_act_286_cplx
type: KineticLaw

425194
local parameters: 568792
local parameters: 568791
notes: kf*PKC_slash_PKC_minus_Ca_minus_DAG-kb*PKC_slash_PKC_minus_DAG_minus_memb_star_
type: KineticLaw

433310
stoichiometry: 1.0
species: 402797
type: SpeciesReference

MODEL9089491423
species: 400558
curated: false
reaction: 407957
reaction: 405017
name: Ajay_Bhalla_2004_PKM_Tuning
length unit: length
species: 403457
reaction: 405297
species: 401117
reaction: 408397
reaction: 406777
reaction: 404577
reaction: 404857
rule: 404417
reaction: 407037
species: 403577
reaction: 406857
reaction: 408117
species: 403777
reaction: 407217
species: 401777
species: 402377
species: 403017
species: 403977
species: 400917
species: 401137
reaction: 407377
species: 402917
reaction: 407697
area units: area
reaction: 405397
species: 400817
reaction: 405557
species: 400637
species: 401617
species: 401037
species: 403137
reaction: 406217
reaction: 405077
species: 402957
time units: 131570
species: 401817
species: 404297
reaction: 405777
reaction: 405377
reaction: 408237
species: 401157
species: 402857
units def: 424842
species: 403997
reaction: 408097
reaction: 408337
species: 401557
species: 402157
reaction: 405937
reaction: 407397
reaction: 404897
species: 400797
reaction: 408057
reaction: 404937
reaction: 407477
reaction: 407077
reaction: 408157
species: 403077
species: 402417
reaction: 407777
reaction: 406277
reaction: 404777
species: 401837
reaction: 405657
species: 404317
reaction: 407457
species: 404077
reaction: 406377
reaction: 406077
reaction: 405157
reaction: 405477
species: 401877
reaction: 405957
type: SBMLModel

428269
local parameters: 569054
local parameters: 569051
notes: kf*Gs_minus_alpha*AC_slash_AC1-kb*AC_slash_AC1_minus_Gs
type: KineticLaw

406817
kinetic law: 430582
product: 430570
product: 430558
reactant: 430546
fast: false
reversible: false
type: Reaction

569182
units: 424962
value: 4.28571E-15
type: LocalParameter

407357
kinetic law: 431897
product: 431884
reactant: 431872
reactant: 431860
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

569332
units: 424878
value: 6.0E-14
type: LocalParameter

406797
kinetic law: 430534
product: 430522
reactant: 430509
reactant: 430497
notes: Kinetics are the same as for the craf_1* activity, ie., k1=5.5e-6, k2=0.42, k3 = 0.105 These are basedo n Force et al PNAS USA 91 1270-1274, 1994., but k1 is scaled up 5x (ie., Km is scaled down 5x to the value used here and for craf_1* activity: Km = 0.1591).
fast: false
reversible: true
type: Reaction

430316
stoichiometry: 1.0
species: 401517
type: SpeciesReference

424974
exponent: 2.0
scale: 0
multipler: 1.0
kind: LITRE
type: SBMLUnit

403817
constant: false
boundary condition: false
has only substance units: false
initial concentration: 2.0
initial amount: NaN
in compartment: 400538
type: Species

400817
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

569038
units: 424878
value: 1.5E-15
type: LocalParameter

433092
stoichiometry: 1.0
species: 402857
type: SpeciesReference

569183
units: 424878
value: 2.4E-14
type: LocalParameter

431438
stoichiometry: 1.0
species: 401417
type: SpeciesReference

427650
local parameters: 569002
local parameters: 568999
notes: kf*CaNAB_minus_Ca4*CaM_minus_TR2_minus_Ca2-kb*PP2B_slash_CaMCa2_minus_CANAB
type: KineticLaw

403897
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

569333
units: 424878
value: 1.5E-14
type: LocalParameter

569079
units: 424878
value: 7.5E-19
type: LocalParameter

569039
units: 424962
value: 7.499925E-14
type: LocalParameter

569220
units: 424878
value: 5.4E-14
type: LocalParameter

401437
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.5
initial amount: NaN
in compartment: 400538
type: Species

569184
units: 424878
value: 6.0E-15
type: LocalParameter

400617
constant: false
boundary condition: false
has only substance units: false
initial concentration: 1.161E-16
initial amount: NaN
in compartment: 400538
type: Species

428330
stoichiometry: 1.0
species: 403777
type: SpeciesReference

402737
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

569078
units: 424878
value: 6.0E-16
type: LocalParameter

432645
local parameters: 569250
notes: k3*CaMKII_slash_tot_CaM_CaMKII_slash_CaM_act_305_slash_CaM_act_305_cplx
type: KineticLaw

426716
stoichiometry: 1.0
species: 402397
type: SpeciesReference

429382
stoichiometry: 1.0
species: 400817
type: SpeciesReference

427748
local parameters: 569010
local parameters: 569007
notes: kf*CaM_minus_Ca4*CaNAB_minus_Ca4-kb*PP2B_slash_CaMCa4_minus_CaNAB
type: KineticLaw

425389
local parameters: 568806
local parameters: 568803
notes: kf*temp_minus_PIP2*PLA2_slash_PLA2_minus_Ca_star_-kb*PLA2_slash_PIP2_minus_Ca_minus_PLA2_star_
type: KineticLaw

432091
local parameters: 569226
local parameters: 569223
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

430522
stoichiometry: 1.0
species: 401617
type: SpeciesReference

568827
units: 424878
value: 3.75E-15
type: LocalParameter

425765
stoichiometry: 1.0
species: 401117
type: SpeciesReference

425340
local parameters: 568802
local parameters: 568799
notes: kf*temp_minus_PIP2*PLA2_slash_PLA2_minus_cytosolic-kb*PLA2_slash_PIP2_minus_PLA2_star_
type: KineticLaw

406257
kinetic law: 429201
product: 429188
product: 429176
reactant: 429164
fast: false
reversible: false
type: Reaction

401357
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

426850
stoichiometry: 1.0
species: 402497
type: SpeciesReference

428488
local parameters: 569074
local parameters: 569071
notes: kf*Ca_input-kb*Ca
type: KineticLaw

568931
units: 424962
value: 3.75003E-17
type: LocalParameter

401917
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.1
initial amount: NaN
in compartment: 400538
type: Species

406577
kinetic law: 429977
product: 429965
product: 429953
reactant: 429940
fast: false
reversible: false
type: Reaction

568826
units: 424878
value: 1.5E-15
type: LocalParameter

406297
kinetic law: 429298
product: 429286
product: 429274
reactant: 429262
fast: false
reversible: false
type: Reaction

428512
stoichiometry: 2.0
species: 403917
type: SpeciesReference

404317
constant: false
boundary condition: true
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

429346
local parameters: 569117
local parameters: 569116
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

428112
stoichiometry: 1.0
species: 403597
type: SpeciesReference

404097
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: 400538
type: Species

425437
local parameters: 568810
local parameters: 568807
notes: kf*DAG*PLA2_slash_PLA2_minus_Ca_star_-kb*PLA2_slash_DAG_minus_Ca_minus_PLA2_star_
type: KineticLaw

432344
stoichiometry: 1.0
species: 402357
type: SpeciesReference

431716
stoichiometry: 1.0
species: 402057
type: SpeciesReference

403277
constant: false
boundary condition: false
has only substance units: false
initial concentration: 1.0
initial amount: NaN
in compartment: 400538
type: Species

427638
stoichiometry: 1.0
species: 403337
type: SpeciesReference

406217
kinetic law: 429104
product: 429092
product: 429080
product: 429068
reactant: 429056
fast: false
reversible: false
type: Reaction

433539
stoichiometry: 1.0
species: 404357
type: SpeciesReference

427541
stoichiometry: 1.0
species: 403237
type: SpeciesReference

427202
stoichiometry: 2.0
species: 403917
type: SpeciesReference

434289
local parameters: 569326
local parameters: 569325
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

434436
local parameters: 569330
notes: k3*AC_slash_PDE1_slash_PDE1_slash_PDE1_cplx
type: KineticLaw

569034
units: 424962
value: 2.7E-14
type: LocalParameter

401857
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

433200
stoichiometry: 1.0
species: 402697
type: SpeciesReference

404017
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

568867
units: 424962
value: 9.000045E-18
type: LocalParameter

433164
stoichiometry: 1.0
species: 402877
type: SpeciesReference

430966
stoichiometry: 1.0
species: 401717
type: SpeciesReference

404137
constant: true
boundary condition: true
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

433951
local parameters: 569303
local parameters: 569300
notes: kcat*AC_slash_AC1_minus_CaM*AC_slash_ATP/(Km+AC_slash_ATP)
type: KineticLaw

425901
stoichiometry: 1.0
species: 404117
type: SpeciesReference

430690
stoichiometry: 1.0
species: 401437
type: SpeciesReference

434580
local parameters: 569338
local parameters: 569335
notes: k1*PKM_slash_AA_pool*PKM_slash_PKM_synthesis-k2*PKM_slash_PKM_synthesis_slash_kenz_slash_kenz_cplx
type: KineticLaw

404057
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0944444444444444
initial amount: NaN
in compartment: 400538
type: Species

403537
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

401177
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

407097
kinetic law: 431270
product: 431258
product: 431246
reactant: 431234
fast: false
reversible: false
type: Reaction

402897
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

568930
units: 424878
value: 1.5E-16
type: LocalParameter

568866
units: 424878
value: 0.0
type: LocalParameter

569035
units: 424962
value: 9.000045E-14
type: LocalParameter

424938
exponent: -2.0
scale: -6
multipler: 1.0
kind: MOLE
type: SBMLUnit

568823
units: 424962
value: 4.499955E-15
type: LocalParameter

431982
stoichiometry: 1.0
species: 402177
type: SpeciesReference

404917
kinetic law: 426110
product: 426097
reactant: 426085
reactant: 426073
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

429916
stoichiometry: 1.0
species: 401057
type: SpeciesReference

568935
units: 424878
value: 1.5E-18
type: LocalParameter

429855
stoichiometry: 1.0
species: 401477
type: SpeciesReference

402097
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

405157
kinetic law: 426656
product: 426644
reactant: 426632
reactant: 426620
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

426351
stoichiometry: 1.0
species: 401657
type: SpeciesReference

427286
stoichiometry: 1.0
species: 402997
type: SpeciesReference

430206
stoichiometry: 1.0
species: 401457
type: SpeciesReference

402057
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

568822
units: 424878
value: 0.0
type: LocalParameter

568790
units: 424878
value: 5.2539E-15
type: LocalParameter

429904
stoichiometry: 1.0
species: 400997
type: SpeciesReference

405117
kinetic law: 426572
product: 426560
reactant: 426548
reactant: 426536
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

431077
local parameters: 569184
notes: k3*MKP_minus_1_slash_MKP1_minus_thr_minus_deph_slash_MKP1_minus_thr_minus_deph_cplx
type: KineticLaw

428197
stoichiometry: 1.0
species: 403897
type: SpeciesReference

428620
stoichiometry: 1.0
species: 401397
type: SpeciesReference

433842
stoichiometry: 1.0
species: 403257
type: SpeciesReference

405197
kinetic law: 426728
product: 426716
reactant: 426704
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

402917
constant: false
boundary condition: false
has only substance units: false
initial concentration: 20.0
initial amount: NaN
in compartment: 400538
type: Species

568863
units: 424878
value: 1.995E-17
type: LocalParameter

425047
stoichiometry: 1.0
species: 403917
type: SpeciesReference

431584
stoichiometry: 1.0
species: 401937
type: SpeciesReference

404957
type: Reaction
reactant: 426170
kinetic law: 426218
product: 426182
product: 426206
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.
product: 426194
fast: false
reversible: true

425715
stoichiometry: 1.0
species: 401157
type: SpeciesReference

427699
local parameters: 569006
local parameters: 569003
notes: kf*CaM_minus_Ca3*CaNAB_minus_Ca4-kb*PP2B_slash_CaMCa3_minus_CaNAB
type: KineticLaw

408197
kinetic law: 433951
modifier: 433939
product: 433926
reactant: 433914
fast: false
reversible: false
type: Reaction

569030
units: 424962
value: 2.7E-14
type: LocalParameter

404997
kinetic law: 426315
product: 426303
reactant: 426291
reactant: 426279
notes: The rate consts give a total binding affinity of only
fast: false
reversible: true
type: Reaction

429456
stoichiometry: 1.0
species: 400877
type: SpeciesReference

405737
kinetic law: 427991
product: 427979
product: 427967
reactant: 427955
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

568862
units: 424878
value: 0.0
type: LocalParameter

426536
stoichiometry: 1.0
species: 401917
type: SpeciesReference

434398
stoichiometry: 1.0
species: 403837
type: SpeciesReference

402957
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

434472
stoichiometry: 1.0
species: 403877
type: SpeciesReference

568934
units: 424878
value: 2.52E-17
type: LocalParameter

433128
local parameters: 569268
notes: k3*PP1_minus_active_slash_Deph_minus_thr306_slash_Deph_minus_thr306_cplx
type: KineticLaw

426692
local parameters: 568922
local parameters: 568919
notes: kf*EGFR_slash_SHC_star_-kb*EGFR_slash_SHC
type: KineticLaw

569031
units: 424878
value: 9.0E-14
type: LocalParameter

400857
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

432561
stoichiometry: 1.0
species: 402677
type: SpeciesReference

434096
local parameters: 569315
local parameters: 569312
notes: kcat*AC_slash_AC1_minus_Gs*AC_slash_ATP/(Km+AC_slash_ATP)
type: KineticLaw

402977
constant: false
boundary condition: false
has only substance units: false
initial concentration: 10.0
initial amount: NaN
in compartment: 400538
type: Species

569155
units: 424962
value: 4.86E-14
type: LocalParameter

431668
stoichiometry: 1.0
species: 401977
type: SpeciesReference

405097
kinetic law: 426523
product: 426510
reactant: 426498
notes: Assume a reasonably good rate for dephosphorylating it, 1/sec
fast: false
reversible: true
type: Reaction

569268
units: 424878
value: 5.25E-16
type: LocalParameter

428161
stoichiometry: 1.0
species: 403657
type: SpeciesReference

433830
stoichiometry: 1.0
species: 403237
type: SpeciesReference

433647
stoichiometry: 1.0
species: 403197
type: SpeciesReference

430121
stoichiometry: 1.0
species: 401177
type: SpeciesReference

404717
kinetic law: 425642
product: 425630
reactant: 425618
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

432416
stoichiometry: 1.0
species: 402297
type: SpeciesReference

405777
kinetic law: 428087
product: 428075
reactant: 428063
reactant: 428051
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

427420
stoichiometry: 1.0
species: 403117
type: SpeciesReference

424854
exponent: -1.0
scale: 0
multipler: 1.0
kind: LITRE
type: SBMLUnit

430448
stoichiometry: 1.0
species: 402837
type: SpeciesReference

429770
stoichiometry: 1.0
species: 400997
type: SpeciesReference

569156
units: 424878
value: 1.8E-15
type: LocalParameter

569269
units: 424962
value: 5.147955E-16
type: LocalParameter

433188
stoichiometry: 1.0
species: 402877
type: SpeciesReference

569204
units: 424962
value: 2.97E-16
type: LocalParameter

427529
stoichiometry: 1.0
species: 403297
type: SpeciesReference

429238
stoichiometry: 1.0
species: 400797
type: SpeciesReference

405057
kinetic law: 426448
product: 426436
reactant: 426424
fast: false
reversible: true
type: Reaction

431378
stoichiometry: 1.0
species: 401477
type: SpeciesReference

433273
local parameters: 569276
local parameters: 569273
notes: k1*CaMKII_slash_CaMKII_minus_thr286*PP1_minus_active-k2*PP1_minus_active_slash_Deph_thr286b_slash_Deph_thr286b_cplx
type: KineticLaw

426110
local parameters: 568870
local parameters: 568867
notes: kf*Gq_slash_G_minus_GDP*Gq_slash_Rec_minus_Glu-kb*Gq_slash_Rec_minus_Glu_minus_Gq
type: KineticLaw

432308
stoichiometry: 1.0
species: 402577
type: SpeciesReference

401937
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

569266
units: 424962
value: 5.147955E-16
type: LocalParameter

569153
units: 424878
value: 1.8E-15
type: LocalParameter

434157
stoichiometry: 1.0
species: 403557
type: SpeciesReference

428209
stoichiometry: 1.0
species: 403637
type: SpeciesReference

426826
local parameters: 568934
local parameters: 568931
notes: kf*Sos_slash_Sos_star_*Sos_slash_Grb2-kb*Sos_slash_Sos_star__dot_Grb2
type: KineticLaw

403317
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

405017
kinetic law: 426363
product: 426351
reactant: 426339
reactant: 426327
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 May 16, 2003 Changed Ras and Raf to synaptic levels, an increase of about 2x for each. To maintain the percentage of complexed Raf, reduced the kf by 2.4 fold to 10.
fast: false
reversible: true
type: Reaction

569202
units: 424878
value: 3.0E-17
type: LocalParameter

569267
units: 424878
value: 2.1E-15
type: LocalParameter

569154
units: 424878
value: 4.5E-16
type: LocalParameter

432465
stoichiometry: 1.0
species: 401077
type: SpeciesReference

427396
stoichiometry: 1.0
species: 402977
type: SpeciesReference

405677
kinetic law: 427845
product: 427833
reactant: 427821
reactant: 427809
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

432392
stoichiometry: 1.0
species: 402337
type: SpeciesReference

430546
stoichiometry: 1.0
species: 401617
type: SpeciesReference

430485
local parameters: 569160
notes: k3*PP1_minus_active_slash_Deph_minus_thr305_slash_Deph_minus_thr305_cplx
type: KineticLaw

407617
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.
reversible: false
fast: false
kinetic law: 432549
reactant: 432501
type: Reaction
product: 432525
product: 432513
modifier: 432537

428051
stoichiometry: 1.0
species: 402137
type: SpeciesReference

408217
kinetic law: 434000
modifier: 433988
product: 433976
reactant: 433963
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

402477
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

432705
stoichiometry: 1.0
species: 402737
type: SpeciesReference

569151
units: 424878
value: 7.2E-14
type: LocalParameter

426572
local parameters: 568910
local parameters: 568907
notes: kf*Ras_slash_inact_minus_GEF*CaM_minus_Ca4-kb*Ras_slash_CaM_minus_GEF
type: KineticLaw

433237
stoichiometry: 1.0
species: 402677
type: SpeciesReference

434229
stoichiometry: 1.0
species: 403737
type: SpeciesReference

430339
local parameters: 569156
local parameters: 569155
notes: k1*MAPK_slash_MAPK_minus_tyr*MAPK_slash_MAPKK_star_-k2*MAPK_slash_MAPKK_star__slash_MAPKKthr_slash_MAPKKthr_cplx
type: KineticLaw

569209
units: 424962
value: 7.42284E-14
type: LocalParameter

425401
stoichiometry: 1.0
species: 400638
type: SpeciesReference

433383
stoichiometry: 1.0
species: 403037
type: SpeciesReference

426584
stoichiometry: 1.0
species: 402077
type: SpeciesReference

402437
constant: false
boundary condition: false
has only substance units: false
initial concentration: 1.0
initial amount: NaN
in compartment: 400538
type: Species

407657
kinetic law: 432645
product: 432633
product: 432621
reactant: 432609
fast: false
reversible: false
type: Reaction

569152
units: 424962
value: 4.86E-14
type: LocalParameter

432031
stoichiometry: 1.0
species: 402137
type: SpeciesReference

431511
local parameters: 569201
local parameters: 569200
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

408257
kinetic law: 434096
modifier: 434084
product: 434072
reactant: 434060
fast: false
reversible: false
type: Reaction

408317
kinetic law: 434241
product: 434229
product: 434217
reactant: 434205
fast: false
reversible: false
type: Reaction

430630
local parameters: 569168
local parameters: 569167
notes: k1*MAPK_slash_MAPKK_minus_ser*MAPK_slash_Raf_minus_GTP_minus_Ras-k2*MAPK_slash_Raf_minus_GTP_minus_Ras_slash_Raf_minus_GTP_minus_Ras_dot_2_slash_Raf_minus_GTP_minus_Ras_dot_2_cplx
type: KineticLaw

429480
stoichiometry: 1.0
species: 400857
type: SpeciesReference

428801
local parameters: 569094
notes: k3*PKC_minus_active_slash_PKC_minus_inact_minus_GAP_slash_PKC_minus_inact_minus_GAP_cplx
type: KineticLaw

569208
units: 424878
value: 3.0E-17
type: LocalParameter

427310
stoichiometry: 1.0
species: 402217
type: SpeciesReference

404357
constant: false
boundary condition: true
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

405357
kinetic law: 427093
product: 427081
reactant: 427069
reactant: 427057
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

428959
stoichiometry: 1.0
species: 400697
type: SpeciesReference

569207
units: 424878
value: 1.2E-16
type: LocalParameter

568830
units: 424878
value: 0.0
type: LocalParameter

403697
constant: false
boundary condition: false
has only substance units: false
initial concentration: 325493.333333333
initial amount: NaN
in compartment: 400557
type: Species

431909
stoichiometry: 1.0
species: 402157
type: SpeciesReference

427833
stoichiometry: 1.0
species: 403417
type: SpeciesReference

568831
units: 424878
value: 2.25E-16
type: LocalParameter

569150
units: 424878
value: 2.88E-13
type: LocalParameter

434000
local parameters: 569307
local parameters: 569304
notes: kcat*AC_slash_AC2_star_*AC_slash_ATP/(Km+AC_slash_ATP)
type: KineticLaw

426048
stoichiometry: 1.0
species: 401257
type: SpeciesReference

427214
stoichiometry: 1.0
species: 403017
type: SpeciesReference

401777
constant: false
boundary condition: false
has only substance units: false
initial concentration: 1.0
initial amount: NaN
in compartment: 400538
type: Species

569319
units: 424842
value: 60.0
type: LocalParameter

407697
kinetic law: 432742
product: 432729
product: 432717
reactant: 432705
fast: false
reversible: false
type: Reaction

425914
stoichiometry: 1.0
species: 401317
type: SpeciesReference

405277
kinetic law: 426910
product: 426898
reactant: 426886
reactant: 426874
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

401017
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

425802
stoichiometry: 1.0
species: 401237
type: SpeciesReference

431330
stoichiometry: 1.0
species: 401837
type: SpeciesReference

428560
stoichiometry: 1.0
species: 404277
type: SpeciesReference

431294
stoichiometry: 1.0
species: 401777
type: SpeciesReference

434616
stoichiometry: 1.0
species: 403977
type: SpeciesReference

402497
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.1
initial amount: NaN
in compartment: 400538
type: Species

569104
units: 424962
value: 9.18E-17
type: LocalParameter

427469
stoichiometry: 1.0
species: 403157
type: SpeciesReference

427785
stoichiometry: 1.0
species: 403397
type: SpeciesReference

433563
local parameters: 569288
local parameters: 569285
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

432188
local parameters: 569229
local parameters: 569228
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

429164
stoichiometry: 1.0
species: 400737
type: SpeciesReference

431945
local parameters: 569218
notes: k3*PKA_minus_active_slash_PKA_minus_phosph_minus_GEF_slash_PKA_minus_phosph_minus_GEF_cplx
type: KineticLaw

431620
stoichiometry: 1.0
species: 401957
type: SpeciesReference

430169
stoichiometry: 1.0
species: 401077
type: SpeciesReference

569261
units: 424878
value: 3.0E-15
type: LocalParameter

431003
stoichiometry: 1.0
species: 401717
type: SpeciesReference

569103
units: 424878
value: 8.7E-16
type: LocalParameter

428015
stoichiometry: 1.0
species: 402137
type: SpeciesReference

569316
units: 424878
value: 8.1E-14
type: LocalParameter

429370
stoichiometry: 1.0
species: 400657
type: SpeciesReference

403677
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

432633
stoichiometry: 1.0
species: 404317
type: SpeciesReference

432972
stoichiometry: 1.0
species: 402817
type: SpeciesReference

425328
stoichiometry: 1.0
species: 400817
type: SpeciesReference

402197
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

432936
local parameters: 569262
notes: k3*CaMKII_slash_tot_autonomous_CaMKII_slash_auton_286_slash_auton_286_cplx
type: KineticLaw

401637
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

569102
units: 424878
value: 3.51E-15
type: LocalParameter

407397
kinetic law: 431994
product: 431982
reactant: 431970
reactant: 431958
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

425497
stoichiometry: 1.0
species: 403917
type: SpeciesReference

434337
local parameters: 569327
notes: k3*AC_slash_cAMP_minus_PDE_star__slash_PDE_star__slash_PDE_star__cplx
type: KineticLaw

569315
units: 424842
value: 20.0
type: LocalParameter

429092
stoichiometry: 1.0
species: 404297
type: SpeciesReference

427105
stoichiometry: 1.0
species: 402677
type: SpeciesReference

406717
kinetic law: 430339
product: 430327
reactant: 430316
reactant: 430304
notes: Rate consts same as for MAPKKtyr.
fast: false
reversible: true
type: Reaction

432815
stoichiometry: 1.0
species: 402657
type: SpeciesReference

404577
kinetic law: 425340
product: 425328
reactant: 425316
reactant: 425304
fast: false
reversible: true
type: Reaction

403637
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

429953
stoichiometry: 1.0
species: 402477
type: SpeciesReference

406077
kinetic law: 428752
product: 428740
reactant: 428728
reactant: 428716
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

430802
stoichiometry: 1.0
species: 401657
type: SpeciesReference

427760
stoichiometry: 1.0
species: 403377
type: SpeciesReference

426266
local parameters: 568882
local parameters: 568879
notes: kf*Gq_slash_G_minus_GDP*Gq_slash_mGluR-kb*Gq_slash_Rec_minus_Gq
type: KineticLaw

430278
stoichiometry: 1.0
species: 401517
type: SpeciesReference

406137
kinetic law: 428899
product: 428886
product: 428874
reactant: 428862
fast: false
reversible: false
type: Reaction

432079
stoichiometry: 1.0
species: 402197
type: SpeciesReference

401517
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

427906
stoichiometry: 1.0
species: 403557
type: SpeciesReference

430678
local parameters: 569169
notes: k3*MAPK_slash_Raf_minus_GTP_minus_Ras_slash_Raf_minus_GTP_minus_Ras_dot_2_slash_Raf_minus_GTP_minus_Ras_dot_2_cplx
type: KineticLaw

569264
units: 424878
value: 2.1E-15
type: LocalParameter

428776
stoichiometry: 1.0
species: 402017
type: SpeciesReference

569159
units: 424878
value: 2.1E-15
type: LocalParameter

407437
kinetic law: 432091
product: 432079
reactant: 432067
reactant: 432055
notes: Same rates as PKA-phosph-I1
fast: false
reversible: true
type: Reaction

408177
kinetic law: 433902
product: 433890
product: 433878
reactant: 433866
fast: false
reversible: false
type: Reaction

430841
stoichiometry: 1.0
species: 401697
type: SpeciesReference

402657
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

569199
units: 424878
value: 9.0E-15
type: LocalParameter

404157
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: 400557
type: Species

569265
units: 424878
value: 5.25E-16
type: LocalParameter

401077
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.73
initial amount: NaN
in compartment: 400538
type: Species

426632
stoichiometry: 1.0
species: 404217
type: SpeciesReference

432103
stoichiometry: 1.0
species: 402197
type: SpeciesReference

428886
stoichiometry: 1.0
species: 404297
type: SpeciesReference

403977
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.00555555555555556
initial amount: NaN
in compartment: 400538
type: Species

407857
kinetic law: 433128
product: 433116
product: 433104
reactant: 433092
fast: false
reversible: false
type: Reaction

569198
units: 424878
value: 3.6E-14
type: LocalParameter

401397
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.5
initial amount: NaN
in compartment: 400538
type: Species

431486
stoichiometry: 1.0
species: 401877
type: SpeciesReference

404777
kinetic law: 425778
product: 425765
product: 425752
reactant: 425740
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

426194
stoichiometry: 1.0
species: 401217
type: SpeciesReference

406437
kinetic law: 429638
product: 429626
reactant: 429614
reactant: 429601
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

569157
units: 424878
value: 4.5E-16
type: LocalParameter

407957
kinetic law: 433371
product: 433359
reactant: 433347
reactant: 433335
notes: From Seki et al ABB 316(2):673-679
fast: false
reversible: true
type: Reaction

569312
units: 424878
value: 2.7E-14
type: LocalParameter

434048
local parameters: 569311
local parameters: 569308
notes: kcat*AC_slash_AC2_minus_Gs*AC_slash_ATP/(Km+AC_slash_ATP)
type: KineticLaw

430061
stoichiometry: 1.0
species: 401077
type: SpeciesReference

425218
stoichiometry: 1.0
species: 400638
type: SpeciesReference

569262
units: 424878
value: 7.5E-16
type: LocalParameter

425121
local parameters: 568788
local parameters: 568787
notes: kf*DAG*PKC_slash_PKC_minus_Ca-kb*PKC_slash_PKC_minus_Ca_minus_DAG
type: KineticLaw

406937
kinetic law: 430881
product: 430868
product: 430855
reactant: 430841
fast: false
reversible: false
type: Reaction

407917
kinetic law: 433273
product: 433261
reactant: 433249
reactant: 433237
fast: false
reversible: true
type: Reaction

569197
units: 424962
value: 2.87415E-15
type: LocalParameter

433455
stoichiometry: 1.0
species: 403057
type: SpeciesReference

430918
stoichiometry: 1.0
species: 401737
type: SpeciesReference

430894
stoichiometry: 1.0
species: 401497
type: SpeciesReference

401597
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

569311
units: 424842
value: 20.0
type: LocalParameter

426315
local parameters: 568886
local parameters: 568883
notes: kf*Gq_slash_Rec_minus_Gq*Gq_slash_mGluRAntag-kb*Gq_slash_Blocked_minus_rec_minus_Gq
type: KineticLaw

569158
units: 424962
value: 5.147955E-16
type: LocalParameter

429274
stoichiometry: 1.0
species: 400657
type: SpeciesReference

569263
units: 424962
value: 5.147955E-16
type: LocalParameter

400777
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

406477
kinetic law: 429734
product: 429722
reactant: 429710
reactant: 429698
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

428911
stoichiometry: 1.0
species: 402977
type: SpeciesReference

569043
units: 424878
value: 1.5E-16
type: LocalParameter

403417
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

427686
stoichiometry: 1.0
species: 403317
type: SpeciesReference

568946
units: 424878
value: 1.5E-14
type: LocalParameter

431210
stoichiometry: 1.0
species: 401817
type: SpeciesReference

426218
local parameters: 568878
local parameters: 568875
notes: kf*Gq_slash_Rec_minus_Glu_minus_Gq-kb*G_star_GTP*BetaGamma*Gq_slash_Rec_minus_Glu
type: KineticLaw

569195
units: 424878
value: 3.6E-14
type: LocalParameter

431402
stoichiometry: 1.0
species: 401857
type: SpeciesReference

569002
units: 424878
value: 1.5E-15
type: LocalParameter

426934
stoichiometry: 1.0
species: 403917
type: SpeciesReference

569042
units: 424878
value: 1.5E-15
type: LocalParameter

569196
units: 424878
value: 9.0E-15
type: LocalParameter

427991
local parameters: 569030
local parameters: 569027
notes: kf*PKA_slash_R2C2_minus_cAMP4-kb*PKA_minus_active*PKA_slash_R2C_minus_cAMP4
type: KineticLaw

568906
units: 424878
value: 0.0
type: LocalParameter

429614
stoichiometry: 1.0
species: 400937
type: SpeciesReference

405517
kinetic law: 427457
product: 427445
reactant: 427433
reactant: 427420
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

426523
local parameters: 568906
local parameters: 568903
notes: kf*Ras_slash_GAP_star_-kb*Ras_slash_GAP
type: KineticLaw

434556
stoichiometry: 1.0
species: 403977
type: SpeciesReference

403217
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

568987
units: 424878
value: 1.5E-15
type: LocalParameter

401977
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

425108
stoichiometry: 1.0
species: 400598
type: SpeciesReference

428342
stoichiometry: 1.0
species: 403737
type: SpeciesReference

569256
units: 424878
value: 9.0E-15
type: LocalParameter

406617
kinetic law: 430085
product: 430073
product: 430061
product: 430049
reactant: 430037
fast: false
reversible: false
type: Reaction

433020
stoichiometry: 1.0
species: 402797
type: SpeciesReference

569003
units: 424962
value: 3.357045E-15
type: LocalParameter

433347
stoichiometry: 1.0
species: 404357
type: SpeciesReference

426412
local parameters: 568894
local parameters: 568891
notes: kf*BetaGamma*Ras_slash_inact_minus_GEF-kb*Ras_slash_GEF_minus_Gprot_minus_bg
type: KineticLaw

405877
kinetic law: 428318
product: 428306
reactant: 428294
reactant: 428282
notes: kb/kf = 1.2 nM so kf = kb/720 = 1.3888 * kb.
fast: false
reversible: true
type: Reaction

426085
stoichiometry: 1.0
species: 401317
type: SpeciesReference

568948
units: 424878
value: 1.5E-14
type: LocalParameter

432140
local parameters: 569227
notes: k3*PKA_minus_active_slash_phosph_minus_PDE_slash_phosph_minus_PDE_cplx
type: KineticLaw

428632
stoichiometry: 1.0
species: 404297
type: SpeciesReference

569083
units: 424878
value: 1.5E-18
type: LocalParameter

569193
units: 424878
value: 9.0E-15
type: LocalParameter

568907
units: 424962
value: 2.99997E-13
type: LocalParameter

427081
stoichiometry: 1.0
species: 402617
type: SpeciesReference

425557
local parameters: 568822
local parameters: 568819
notes: kf*PLA2_slash_PLA2_star_-kb*PLA2_slash_PLA2_minus_cytosolic
type: KineticLaw

569255
units: 424878
value: 3.6E-14
type: LocalParameter

431102
stoichiometry: 1.0
species: 401777
type: SpeciesReference

408477
kinetic law: 434628
product: 434616
product: 434604
reactant: 434592
fast: false
reversible: false
type: Reaction

568986
units: 424878
value: 1.5E-16
type: LocalParameter

432200
stoichiometry: 1.0
species: 402257
type: SpeciesReference

426363
local parameters: 568890
local parameters: 568887
notes: kf*MAPK_slash_craf_minus_1_star_*Ras_slash_GTP_minus_Ras-kb*MAPK_slash_Raf_star__minus_GTP_minus_Ras
type: KineticLaw

568947
units: 424962
value: 1.799955E-14
type: LocalParameter

428996
local parameters: 569103
notes: k3*PKC_minus_active_slash_PKC_minus_phosph_minus_neurogranin_slash_PKC_minus_phosph_minus_neurogranin_cplx
type: KineticLaw

569320
units: 424962
value: 3.78E-15
type: LocalParameter

433419
local parameters: 569280
notes: k3*CaM_po_Ca_pc_n_minus_CaNAB_slash_dephosph_neurogranin_slash_dephosph_neurogranin_cplx
type: KineticLaw

405837
kinetic law: 428221
product: 428209
reactant: 428197
reactant: 428185
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

569082
units: 424878
value: 0.0
type: LocalParameter

400897
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

428233
stoichiometry: 1.0
species: 403897
type: SpeciesReference

569194
units: 424962
value: 2.87415E-15
type: LocalParameter

401237
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

569254
units: 424962
value: 2.571345E-16
type: LocalParameter

432754
stoichiometry: 1.0
species: 402677
type: SpeciesReference

568942
units: 424878
value: 2.52E-17
type: LocalParameter

429650
stoichiometry: 1.0
species: 400957
type: SpeciesReference

400557
constant: true
size: 2.5E-21
spatial dimensions: 3.0
type: Compartment

424926
exponent: 3.0
scale: 0
multipler: 1.0
kind: LITRE
type: SBMLUnit

569047
units: 424962
value: 7.499925E-13
type: LocalParameter

404877
kinetic law: 426024
product: 426012
reactant: 426000
reactant: 425987
notes: kf == kg3 = 1e-5 /cell/sec. As usual, there is no back-reaction kb = 0
fast: false
reversible: true
type: Reaction

430376
stoichiometry: 1.0
species: 401517
type: SpeciesReference

427882
stoichiometry: 1.0
species: 403437
type: SpeciesReference

404637
kinetic law: 425473
product: 425461
reactant: 425449
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

406697
kinetic law: 430291
product: 430278
product: 430266
reactant: 430254
fast: false
reversible: false
type: Reaction

568871
units: 424962
value: 2.520045E-14
type: LocalParameter

431090
stoichiometry: 1.0
species: 401417
type: SpeciesReference

434652
stoichiometry: 1.0
species: 404017
type: SpeciesReference

425951
stoichiometry: 1.0
species: 401237
type: SpeciesReference

434592
stoichiometry: 1.0
species: 403997
type: SpeciesReference

402837
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

569006
units: 424878
value: 1.5E-15
type: LocalParameter

428306
stoichiometry: 1.0
species: 403717
type: SpeciesReference

403577
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

400558
constant: false
boundary condition: false
has only substance units: false
initial concentration: 3.72077777777778E-17
initial amount: NaN
in compartment: 400538
type: Species

569046
units: 424878
value: 0.0
type: LocalParameter

569007
units: 424962
value: 9.000045E-13
type: LocalParameter

568870
units: 424878
value: 1.5E-19
type: LocalParameter

432284
local parameters: 569232
local parameters: 569231
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

568983
units: 424962
value: 7.499655E-13
type: LocalParameter

429128
stoichiometry: 1.0
species: 404297
type: SpeciesReference

404837
kinetic law: 425926
product: 425914
reactant: 425901
reactant: 425889
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

430738
stoichiometry: 1.0
species: 401677
type: SpeciesReference

425666
stoichiometry: 1.0
species: 404157
type: SpeciesReference

427577
stoichiometry: 2.0
species: 403917
type: SpeciesReference

434277
stoichiometry: 1.0
species: 403797
type: SpeciesReference

425096
stoichiometry: 1.0
species: 400558
type: SpeciesReference

568902
units: 424878
value: 0.0
type: LocalParameter

408077
kinetic law: 433659
product: 433647
reactant: 433635
reactant: 433623
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

569192
units: 424878
value: 3.6E-14
type: LocalParameter

426970
stoichiometry: 1.0
species: 403917
type: SpeciesReference

405397
kinetic law: 427177
product: 427165
reactant: 427153
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

401297
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.3
initial amount: NaN
in compartment: 400538
type: Species

429056
stoichiometry: 1.0
species: 400717
type: SpeciesReference

568982
units: 424878
value: 0.0
type: LocalParameter

405917
kinetic law: 428403
product: 428391
reactant: 428379
reactant: 428367
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

429334
stoichiometry: 1.0
species: 400837
type: SpeciesReference

430776
local parameters: 569172
notes: k3*MAPK_slash_Raf_star__minus_GTP_minus_Ras_slash_Raf_star__minus_GTP_minus_Ras_dot_1_slash_Raf_star__minus_GTP_minus_Ras_dot_1_cplx
type: KineticLaw

568903
units: 424878
value: 1.5E-16
type: LocalParameter

569087
units: 424962
value: 1.499985E-15
type: LocalParameter

425778
local parameters: 568842
local parameters: 568839
notes: kf*PLCbeta_slash_PLC_minus_Ca_minus_Gq-kb*G_star_GDP*PLCbeta_slash_PLC_minus_Ca
type: KineticLaw

429734
local parameters: 569132
local parameters: 569131
notes: k1*PLA2_slash_PLA2_minus_cytosolic*MAPK_star_-k2*MAPK_star__slash_MAPK_star__slash_MAPK_star__cplx
type: KineticLaw

433720
stoichiometry: 1.0
species: 403137
type: SpeciesReference

427045
local parameters: 568950
local parameters: 568949
notes: kf*PLC_g_slash_Ca_dot_PLC_g_star_-kb*PLC_g_slash_Ca_dot_PLC_g
type: KineticLaw

568943
units: 424962
value: 2.7E-13
type: LocalParameter

431788
stoichiometry: 1.0
species: 402117
type: SpeciesReference

427141
local parameters: 568958
local parameters: 568955
notes: kf*CaMKII_slash_CaMKII_minus_thr286*CaM_minus_Ca4-kb*CaMKII_slash_CaMKII_minus_thr286_star__minus_CaM
type: KineticLaw

431198
stoichiometry: 1.0
species: 401777
type: SpeciesReference

569258
units: 424962
value: 2.142855E-17
type: LocalParameter

430230
stoichiometry: 1.0
species: 401537
type: SpeciesReference

569086
units: 424878
value: 0.0
type: LocalParameter

400519
constant: true
size: 1.0E-18
spatial dimensions: 3.0
type: Compartment

426473
stoichiometry: 1.0
species: 401997
type: SpeciesReference

407757
kinetic law: 432888
product: 432875
reactant: 432863
reactant: 432851
fast: false
reversible: true
type: Reaction

433491
stoichiometry: 1.0
species: 403097
type: SpeciesReference

568875
units: 424878
value: 1.5E-17
type: LocalParameter

426704
stoichiometry: 1.0
species: 402297
type: SpeciesReference

431596
stoichiometry: 1.0
species: 401957
type: SpeciesReference

425703
stoichiometry: 1.0
species: 401117
type: SpeciesReference

405237
kinetic law: 426826
product: 426814
reactant: 426802
reactant: 426790
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

428728
stoichiometry: 1.0
species: 404297
type: SpeciesReference

425059
stoichiometry: 1.0
species: 400558
type: SpeciesReference

405457
kinetic law: 427323
product: 427310
reactant: 427298
reactant: 427286
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

428415
stoichiometry: 1.0
species: 401397
type: SpeciesReference

425377
stoichiometry: 1.0
species: 400857
type: SpeciesReference

434484
local parameters: 569332
local parameters: 569331
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

426680
stoichiometry: 1.0
species: 402357
type: SpeciesReference

431258
stoichiometry: 1.0
species: 401777
type: SpeciesReference

434386
local parameters: 569329
local parameters: 569328
notes: k1*cAMP*AC_slash_PDE1-k2*AC_slash_PDE1_slash_PDE1_slash_PDE1_cplx
type: KineticLaw

433080
local parameters: 569267
local parameters: 569266
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

568874
units: 424878
value: 1.5E-16
type: LocalParameter

407797
kinetic law: 432984
product: 432972
reactant: 432960
reactant: 432948
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

402157
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

427711
stoichiometry: 1.0
species: 402217
type: SpeciesReference

402337
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

426741
stoichiometry: 1.0
species: 402457
type: SpeciesReference

429843
stoichiometry: 1.0
species: 401037
type: SpeciesReference

431994
local parameters: 569220
local parameters: 569219
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

428391
stoichiometry: 1.0
species: 403857
type: SpeciesReference

429443
local parameters: 569120
local parameters: 569119
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

568835
units: 424962
value: 3.78E-14
type: LocalParameter

426158
local parameters: 568874
local parameters: 568871
notes: kf*Glu*Gq_slash_Rec_minus_Gq-kb*Gq_slash_Rec_minus_Glu_minus_Gq
type: KineticLaw

433878
stoichiometry: 1.0
species: 403097
type: SpeciesReference

431897
local parameters: 569216
local parameters: 569215
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

430013
stoichiometry: 1.0
species: 401137
type: SpeciesReference

427250
stoichiometry: 1.0
species: 403917
type: SpeciesReference

432248
stoichiometry: 1.0
species: 402557
type: SpeciesReference

568834
units: 424878
value: 0.0
type: LocalParameter

429540
local parameters: 569126
local parameters: 569123
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

430412
stoichiometry: 1.0
species: 402797
type: SpeciesReference

431836
stoichiometry: 1.0
species: 402097
type: SpeciesReference

403157
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

430954
stoichiometry: 1.0
species: 401457
type: SpeciesReference

401557
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

568879
units: 424962
value: 9.000045E-16
type: LocalParameter

569253
units: 424878
value: 7.5E-16
type: LocalParameter

407477
kinetic law: 432188
product: 432176
reactant: 432164
reactant: 432152
fast: false
reversible: true
type: Reaction

432791
local parameters: 569255
local parameters: 569254
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

434448
stoichiometry: 1.0
species: 403557
type: SpeciesReference

428125
stoichiometry: 1.0
species: 403577
type: SpeciesReference

400737
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

432452
stoichiometry: 1.0
species: 400638
type: SpeciesReference

402617
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

432525
stoichiometry: 1.0
species: 401077
type: SpeciesReference

569212
units: 424962
value: 2.97E-16
type: LocalParameter

426000
stoichiometry: 1.0
species: 401217
type: SpeciesReference

406177
kinetic law: 428996
product: 428984
product: 428972
reactant: 428959
fast: false
reversible: false
type: Reaction

427602
local parameters: 568998
local parameters: 568995
notes: kf*PP2B_slash_CaNAB*Ca^2-kb*PP2B_slash_CaNAB_minus_Ca2
type: KineticLaw

406877
kinetic law: 430726
product: 430714
reactant: 430702
reactant: 430690
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

568878
units: 424914
value: 0.0
type: LocalParameter

404197
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: 400538
type: Species

569252
units: 424878
value: 3.0E-15
type: LocalParameter

403477
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

406977
kinetic law: 430978
product: 430966
product: 430954
reactant: 430942
fast: false
reversible: false
type: Reaction

428451
local parameters: 569070
local parameters: 569067
notes: kf*MAPK_slash_craf_minus_1*Ras_slash_GTP_minus_Ras-kb*MAPK_slash_Raf_minus_GTP_minus_Ras
type: KineticLaw

569213
units: 424878
value: 1.2E-16
type: LocalParameter

426790
stoichiometry: 1.0
species: 402477
type: SpeciesReference

403077
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

424890
exponent: 1.0
scale: 0
multipler: 1.0
kind: LITRE
type: SBMLUnit

403197
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

568949
units: 424878
value: 7.5E-17
type: LocalParameter

425840
stoichiometry: 1.0
species: 403917
type: SpeciesReference

407017
kinetic law: 431077
product: 431065
product: 431052
reactant: 431039
fast: false
reversible: false
type: Reaction

427359
stoichiometry: 1.0
species: 402937
type: SpeciesReference

431150
stoichiometry: 1.0
species: 401397
type: SpeciesReference

404217
constant: true
boundary condition: true
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

429504
stoichiometry: 1.0
species: 404077
type: SpeciesReference

569251
units: 424962
value: 3.30102E-17
type: LocalParameter

426862
local parameters: 568938
local parameters: 568935
notes: kf*Sos_slash_Sos_star_-kb*Sos_slash_Sos
type: KineticLaw

433769
stoichiometry: 1.0
species: 403217
type: SpeciesReference

403937
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

569210
units: 424878
value: 6.0E-14
type: LocalParameter

568839
units: 424878
value: 1.995E-17
type: LocalParameter

408137
kinetic law: 433806
product: 433793
product: 433781
reactant: 433769
fast: false
reversible: false
type: Reaction

425449
stoichiometry: 1.0
species: 400657
type: SpeciesReference

431728
stoichiometry: 1.0
species: 401997
type: SpeciesReference

432863
stoichiometry: 1.0
species: 404337
type: SpeciesReference

404257
constant: true
boundary condition: true
has only substance units: false
initial concentration: 1.0
initial amount: NaN
in compartment: 400538
type: Species

432356
stoichiometry: 1.0
species: 402297
type: SpeciesReference

427943
local parameters: 569026
local parameters: 569023
notes: kf*cAMP*PKA_slash_R2C2_minus_cAMP3-kb*PKA_slash_R2C2_minus_cAMP4
type: KineticLaw

569250
units: 424878
value: 9.0E-15
type: LocalParameter

407117
kinetic law: 431318
product: 431306
reactant: 431294
reactant: 431282
fast: false
reversible: true
type: Reaction

402697
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

568838
units: 424878
value: 1.5E-15
type: LocalParameter

569211
units: 424878
value: 1.5E-14
type: LocalParameter

407057
kinetic law: 431174
product: 431162
product: 431150
reactant: 431138
fast: false
reversible: false
type: Reaction

428524
stoichiometry: 1.0
species: 404017
type: SpeciesReference

430594
stoichiometry: 1.0
species: 401577
type: SpeciesReference

569278
units: 424962
value: 5.004045E-16
type: LocalParameter

434169
stoichiometry: 1.0
species: 403737
type: SpeciesReference

403737
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.45
initial amount: NaN
in compartment: 400538
type: Species

569165
units: 424878
value: 1.8E-15
type: LocalParameter

434301
stoichiometry: 1.0
species: 403797
type: SpeciesReference

425461
stoichiometry: 1.0
species: 404077
type: SpeciesReference

405977
kinetic law: 428536
product: 428524
reactant: 428512
reactant: 428500
fast: false
reversible: true
type: Reaction

426838
stoichiometry: 1.0
species: 402477
type: SpeciesReference

425889
stoichiometry: 1.0
species: 401297
type: SpeciesReference

569279
units: 424878
value: 4.005E-15
type: LocalParameter

401737
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

569166
units: 424878
value: 4.5E-16
type: LocalParameter

425790
stoichiometry: 1.0
species: 401097
type: SpeciesReference

427384
stoichiometry: 1.0
species: 402957
type: SpeciesReference

402397
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

403777
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

430497
stoichiometry: 1.0
species: 401437
type: SpeciesReference

401277
constant: false
boundary condition: false
has only substance units: false
initial concentration: 1.0
initial amount: NaN
in compartment: 400538
type: Species

430558
stoichiometry: 1.0
species: 401577
type: SpeciesReference

406237
kinetic law: 429152
product: 429140
reactant: 429128
reactant: 429116
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

431560
local parameters: 569202
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

569167
units: 424962
value: 1.41426E-14
type: LocalParameter

428173
local parameters: 569046
local parameters: 569043
notes: kf*AC_slash_AC2_star_-kb*AC_slash_AC2
type: KineticLaw

406997
kinetic law: 431027
product: 431015
reactant: 431003
reactant: 430990
notes: See MKP1-tyr-deph
fast: false
reversible: true
type: Reaction

404077
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: 400538
type: Species

432404
stoichiometry: 1.0
species: 402377
type: SpeciesReference

426778
local parameters: 568930
local parameters: 568927
notes: kf*Sos_slash_Sos_dot_Grb2*EGFR_slash_SHC_star_-kb*Shc_star__dot_Sos_dot_Grb2
type: KineticLaw

400957
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

433659
local parameters: 569291
local parameters: 569290
notes: k1*PP1_slash_I1_star_*PP2A-k2*PP2A_slash_PP2A_minus_dephosph_minus_I1_slash_PP2A_minus_dephosph_minus_I1_cplx
type: KineticLaw

433926
stoichiometry: 1.0
species: 403557
type: SpeciesReference

427505
local parameters: 568990
local parameters: 568987
notes: kf*PP1_slash_PP1_minus_I1-kb*PP1_minus_active*PP1_slash_I1
type: KineticLaw

433599
stoichiometry: 1.0
species: 404357
type: SpeciesReference

433176
local parameters: 569270
local parameters: 569269
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

569168
units: 424878
value: 1.8E-15
type: LocalParameter

400997
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

405637
kinetic law: 427748
product: 427735
reactant: 427723
reactant: 427711
fast: false
reversible: true
type: Reaction

404897
kinetic law: 426061
product: 426048
reactant: 426036
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

406197
kinetic law: 429044
product: 429032
reactant: 429020
reactant: 429008
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

433261
stoichiometry: 1.0
species: 402897
type: SpeciesReference

429879
local parameters: 569139
notes: k3*MAPK_star__slash_MAPK_star__minus_feedback_slash_MAPK_star__minus_feedback_cplx
type: KineticLaw

427517
stoichiometry: 2.0
species: 403917
type: SpeciesReference

406657
kinetic law: 430194
product: 430182
product: 430169
product: 430157
reactant: 430145
fast: false
reversible: false
type: Reaction

405817
kinetic law: 428173
product: 428161
reactant: 428149
notes: Random rate.
fast: false
reversible: true
type: Reaction

568842
units: 424962
value: 0.0
type: LocalParameter

400637
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0555555555555556
initial amount: NaN
in compartment: 400538
type: Species

406377
kinetic law: 429492
product: 429480
product: 429468
reactant: 429456
fast: false
reversible: false
type: Reaction

569308
units: 424878
value: 2.7E-14
type: LocalParameter

427493
stoichiometry: 1.0
species: 403097
type: SpeciesReference

401497
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

431958
stoichiometry: 1.0
species: 403097
type: SpeciesReference

427298
stoichiometry: 1.0
species: 403917
type: SpeciesReference

569162
units: 424962
value: 1.41426E-14
type: LocalParameter

407277
kinetic law: 431704
product: 431692
reactant: 431680
reactant: 431668
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

407337
kinetic law: 431848
product: 431836
product: 431824
reactant: 431812
fast: false
reversible: false
type: Reaction

434012
stoichiometry: 1.0
species: 404237
type: SpeciesReference

568843
units: 424962
value: 3.78E-15
type: LocalParameter

431450
stoichiometry: 1.0
species: 401777
type: SpeciesReference

569307
units: 424842
value: 20.1152893440692
type: LocalParameter

425926
local parameters: 568854
local parameters: 568851
notes: kf*Gq_slash_mGluR*Glu-kb*Gq_slash_Rec_minus_Glu
type: KineticLaw

427821
stoichiometry: 1.0
species: 403557
type: SpeciesReference

426036
stoichiometry: 1.0
species: 401237
type: SpeciesReference

427226
local parameters: 568966
local parameters: 568963
notes: kf*CaM_slash_CaM*Ca^2-kb*CaM_minus_TR2_minus_Ca2
type: KineticLaw

406337
kinetic law: 429395
product: 429382
product: 429370
reactant: 429358
fast: false
reversible: false
type: Reaction

432717
stoichiometry: 1.0
species: 402637
type: SpeciesReference

426560
stoichiometry: 1.0
species: 402097
type: SpeciesReference

425413
stoichiometry: 1.0
species: 400777
type: SpeciesReference

426668
stoichiometry: 1.0
species: 402377
type: SpeciesReference

433976
stoichiometry: 1.0
species: 403557
type: SpeciesReference

428063
stoichiometry: 1.0
species: 403517
type: SpeciesReference

404677
kinetic law: 425557
product: 425545
reactant: 425533
fast: false
reversible: true
type: Reaction

427979
stoichiometry: 1.0
species: 403477
type: SpeciesReference

402137
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

433225
local parameters: 569271
notes: k3*PP1_minus_active_slash_Deph_minus_thr286c_slash_Deph_minus_thr286c_cplx
type: KineticLaw

402037
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.01
initial amount: NaN
in compartment: 400538
type: Species

402757
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

426596
stoichiometry: 1.0
species: 401917
type: SpeciesReference

433371
local parameters: 569279
local parameters: 569278
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

401417
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

431390
stoichiometry: 1.0
species: 401777
type: SpeciesReference

428813
stoichiometry: 1.0
species: 401917
type: SpeciesReference

428680
stoichiometry: 1.0
species: 401417
type: SpeciesReference

429589
local parameters: 569127
notes: k3*PLA2_slash_DAG_minus_Ca_minus_PLA2_star__slash_kenz_slash_kenz_cplx
type: KineticLaw

429989
stoichiometry: 1.0
species: 404177
type: SpeciesReference

431523
stoichiometry: 1.0
species: 401897
type: SpeciesReference

405577
kinetic law: 427602
product: 427589
reactant: 427577
reactant: 427565
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

434410
stoichiometry: 1.0
species: 403697
type: SpeciesReference

404937
kinetic law: 426158
product: 426146
reactant: 426134
reactant: 426122
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

432984
local parameters: 569264
local parameters: 569263
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

434520
stoichiometry: 1.0
species: 403857
type: SpeciesReference

425316
stoichiometry: 1.0
species: 400757
type: SpeciesReference

432621
stoichiometry: 1.0
species: 402657
type: SpeciesReference

427189
stoichiometry: 1.0
species: 402917
type: SpeciesReference

431740
stoichiometry: 1.0
species: 402037
type: SpeciesReference

428027
stoichiometry: 1.0
species: 403497
type: SpeciesReference

569304
units: 424878
value: 1.05E-14
type: LocalParameter

568951
units: 424962
value: 7.499925E-14
type: LocalParameter

432924
stoichiometry: 1.0
species: 404337
type: SpeciesReference

407557
kinetic law: 432380
product: 432368
reactant: 432356
reactant: 432344
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

569270
units: 424878
value: 2.1E-15
type: LocalParameter

569238
units: 424878
value: 2.1E-14
type: LocalParameter

427773
stoichiometry: 1.0
species: 403557
type: SpeciesReference

427117
stoichiometry: 1.0
species: 402217
type: SpeciesReference

429080
stoichiometry: 1.0
species: 402957
type: SpeciesReference

434349
stoichiometry: 1.0
species: 403557
type: SpeciesReference

433708
local parameters: 569292
notes: k3*PP2A_slash_PP2A_minus_dephosph_minus_I1_slash_PP2A_minus_dephosph_minus_I1_cplx
type: KineticLaw

569303
units: 424842
value: 20.0
type: LocalParameter

429407
stoichiometry: 1.0
species: 404077
type: SpeciesReference

407517
kinetic law: 432284
product: 432272
reactant: 432260
reactant: 432248
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

429201
local parameters: 569109
notes: k3*PKC_minus_active_slash_phosph_minus_AC2_slash_phosph_minus_AC2_cplx
type: KineticLaw

569271
units: 424878
value: 5.25E-16
type: LocalParameter

426291
stoichiometry: 1.0
species: 404197
type: SpeciesReference

432827
stoichiometry: 1.0
species: 404337
type: SpeciesReference

434121
stoichiometry: 1.0
species: 403557
type: SpeciesReference

408377
kinetic law: 434386
product: 434374
reactant: 434361
reactant: 434349
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

400678
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

403037
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

431282
stoichiometry: 1.0
species: 401577
type: SpeciesReference

407597
modifier: 432477
reversible: false
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.
fast: false
reactant: 432440
product: 432452
product: 432465
kinetic law: 432489
type: Reaction

425814
stoichiometry: 1.0
species: 401197
type: SpeciesReference

428572
local parameters: 569082
local parameters: 569079
notes: kf*PKC_slash_PKM_minus_zeta-kb*PKM_slash_degraded_PKM
type: KineticLaw

434604
stoichiometry: 1.0
species: 400637
type: SpeciesReference

408057
kinetic law: 433611
product: 433599
product: 433587
reactant: 433575
fast: false
reversible: false
type: Reaction

430906
stoichiometry: 1.0
species: 401717
type: SpeciesReference

431342
stoichiometry: 1.0
species: 401437
type: SpeciesReference

427457
local parameters: 568986
local parameters: 568983
notes: kf*PP1_slash_I1_star_*PP1_minus_active-kb*PP1_slash_PP1_minus_I1_star_
type: KineticLaw

425280
stoichiometry: 1.0
species: 400777
type: SpeciesReference

424950
exponent: -1.0
scale: 0
multipler: 1.0
kind: SECOND
type: SBMLUnit

405417
kinetic law: 427226
product: 427214
reactant: 427202
reactant: 427189
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

433551
stoichiometry: 1.0
species: 403077
type: SpeciesReference

429176
stoichiometry: 1.0
species: 403617
type: SpeciesReference

431632
stoichiometry: 1.0
species: 401977
type: SpeciesReference

432176
stoichiometry: 1.0
species: 402257
type: SpeciesReference

568950
units: 424878
value: 0.0
type: LocalParameter

401117
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

403597
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.02
initial amount: NaN
in compartment: 400538
type: Species

429698
stoichiometry: 1.0
species: 400757
type: SpeciesReference

427797
local parameters: 569014
local parameters: 569011
notes: kf*PKA_slash_R2C2*cAMP-kb*PKA_slash_R2C2_minus_cAMP
type: KineticLaw

425521
local parameters: 568818
local parameters: 568815
notes: kf*PLA2_slash_PLA2_star_*Ca-kb*PLA2_slash_PLA2_star__minus_Ca
type: KineticLaw

404617
kinetic law: 425437
product: 425425
reactant: 425413
reactant: 425401
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

408017
kinetic law: 433515
product: 433503
product: 433491
reactant: 433479
fast: false
reversible: false
type: Reaction

431015
stoichiometry: 1.0
species: 401757
type: SpeciesReference

408337
kinetic law: 434289
product: 434277
reactant: 434265
reactant: 434253
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

430157
stoichiometry: 1.0
species: 400638
type: SpeciesReference

400638
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

433611
local parameters: 569289
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

569273
units: 424962
value: 5.147955E-16
type: LocalParameter

426182
stoichiometry: 1.0
species: 401237
type: SpeciesReference

430881
local parameters: 569178
notes: k3*MAPK_slash_Raf_star__minus_GTP_minus_Ras_slash_Raf_star__minus_GTP_minus_Ras_dot_2_slash_Raf_star__minus_GTP_minus_Ras_dot_2_cplx
type: KineticLaw

428874
stoichiometry: 1.0
species: 401937
type: SpeciesReference

408417
kinetic law: 434484
product: 434472
reactant: 434460
reactant: 434448
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

401677
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

425133
stoichiometry: 1.0
species: 400558
type: SpeciesReference

569169
units: 424878
value: 4.5E-16
type: LocalParameter

569300
units: 424878
value: 2.7E-14
type: LocalParameter

430073
stoichiometry: 1.0
species: 401117
type: SpeciesReference

425206
stoichiometry: 1.0
species: 400618
type: SpeciesReference

433443
stoichiometry: 1.0
species: 404357
type: SpeciesReference

429940
stoichiometry: 1.0
species: 401057
type: SpeciesReference

428923
stoichiometry: 1.0
species: 404297
type: SpeciesReference

426327
stoichiometry: 1.0
species: 401417
type: SpeciesReference

429286
stoichiometry: 1.0
species: 400777
type: SpeciesReference

434689
stoichiometry: 1.0
species: 404037
type: SpeciesReference

430266
stoichiometry: 1.0
species: 401497
type: SpeciesReference

426254
stoichiometry: 1.0
species: 401337
type: SpeciesReference

404497
kinetic law: 425157
product: 425145
reactant: 425133
fast: false
reversible: true
type: Reaction

569050
units: 424878
value: 1.5E-15
type: LocalParameter

402537
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

569276
units: 424878
value: 2.1E-15
type: LocalParameter

430666
stoichiometry: 1.0
species: 401597
type: SpeciesReference

432067
stoichiometry: 1.0
species: 402137
type: SpeciesReference

428764
stoichiometry: 1.0
species: 400677
type: SpeciesReference

433068
stoichiometry: 1.0
species: 402857
type: SpeciesReference

428282
stoichiometry: 1.0
species: 403897
type: SpeciesReference

402577
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

433503
stoichiometry: 1.0
species: 404357
type: SpeciesReference

403437
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

431499
stoichiometry: 1.0
species: 401897
type: SpeciesReference

426303
stoichiometry: 1.0
species: 401377
type: SpeciesReference

405497
kinetic law: 427408
product: 427396
reactant: 427384
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

569051
units: 424962
value: 1.89E-13
type: LocalParameter

426620
stoichiometry: 1.0
species: 402277
type: SpeciesReference

404457
kinetic law: 425071
product: 425059
reactant: 425047
reactant: 425035
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

569277
units: 424878
value: 5.25E-16
type: LocalParameter

403297
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

428972
stoichiometry: 1.0
species: 402957
type: SpeciesReference

428644
stoichiometry: 1.0
species: 400658
type: SpeciesReference

433335
stoichiometry: 1.0
species: 402957
type: SpeciesReference

407177
kinetic law: 431462
product: 431450
product: 431438
reactant: 431426
fast: false
reversible: false
type: Reaction

426400
stoichiometry: 1.0
species: 401877
type: SpeciesReference

426073
stoichiometry: 1.0
species: 401277
type: SpeciesReference

430990
stoichiometry: 1.0
species: 400997
type: SpeciesReference

425569
stoichiometry: 1.0
species: 403917
type: SpeciesReference

432212
stoichiometry: 1.0
species: 401977
type: SpeciesReference

428355
local parameters: 569062
local parameters: 569059
notes: kf*AC_slash_cAMP_minus_PDE_star_-kb*AC_slash_cAMP_minus_PDE
type: KineticLaw

568998
units: 424878
value: 1.5E-15
type: LocalParameter

569095
units: 424962
value: 9.000045E-15
type: LocalParameter

406597
kinetic law: 430025
product: 430013
reactant: 430001
reactant: 429989
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

430049
stoichiometry: 1.0
species: 400638
type: SpeciesReference

568919
units: 424878
value: 2.50005E-18
type: LocalParameter

401337
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

426983
stoichiometry: 1.0
species: 402537
type: SpeciesReference

428984
stoichiometry: 1.0
species: 404297
type: SpeciesReference

568959
units: 424878
value: 4.5E-18
type: LocalParameter

433407
stoichiometry: 1.0
species: 404357
type: SpeciesReference

424998
exponent: -1.0
scale: 0
multipler: 1.0
kind: SECOND
type: SBMLUnit

426375
stoichiometry: 1.0
species: 401217
type: SpeciesReference

404797
kinetic law: 425827
product: 425814
reactant: 425802
reactant: 425790
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

406557
kinetic law: 429928
product: 429916
reactant: 429904
reactant: 429892
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

406277
kinetic law: 429250
product: 429238
reactant: 429226
reactant: 429214
notes: 10 x raise oct22 12 x oct 24, set k2 = 4 * k3
fast: false
reversible: true
type: Reaction

401377
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

569242
units: 424878
value: 8.55E-14
type: LocalParameter

432766
stoichiometry: 1.0
species: 404337
type: SpeciesReference

407137
kinetic law: 431366
product: 431354
product: 431342
reactant: 431330
fast: false
reversible: false
type: Reaction

425170
stoichiometry: 1.0
species: 400598
type: SpeciesReference

403257
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

407977
kinetic law: 433419
product: 433407
product: 433395
reactant: 433383
fast: false
reversible: false
type: Reaction

569094
units: 424878
value: 6.0E-15
type: LocalParameter

405317
kinetic law: 427008
product: 426996
reactant: 426983
reactant: 426970
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

428245
stoichiometry: 1.0
species: 403597
type: SpeciesReference

569055
units: 424962
value: 1.2499245E-12
type: LocalParameter

402877
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

427674
stoichiometry: 1.0
species: 403237
type: SpeciesReference

407217
kinetic law: 431560
product: 431547
product: 431535
reactant: 431523
fast: false
reversible: false
type: Reaction

568958
units: 424878
value: 1.5E-16
type: LocalParameter

404037
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

569245
units: 424842
value: 19.7916666666667
type: LocalParameter

426946
stoichiometry: 1.0
species: 402557
type: SpeciesReference

569014
units: 424878
value: 4.95E-14
type: LocalParameter

400597
constant: false
boundary condition: false
has only substance units: false
initial concentration: 9.43511111111111E-21
initial amount: NaN
in compartment: 400538
type: Species

569093
units: 424878
value: 2.4E-14
type: LocalParameter

426206
stoichiometry: 1.0
species: 401317
type: SpeciesReference

430618
stoichiometry: 1.0
species: 401637
type: SpeciesReference

401837
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

432669
stoichiometry: 1.0
species: 404317
type: SpeciesReference

569054
units: 424878
value: 1.5E-15
type: LocalParameter

401877
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

429626
stoichiometry: 1.0
species: 400957
type: SpeciesReference

568999
units: 424962
value: 3.600045E-16
type: LocalParameter

433032
local parameters: 569265
notes: k3*PP1_minus_active_slash_Deph_minus_thr286_slash_Deph_minus_thr286_cplx
type: KineticLaw

400598
constant: false
boundary condition: false
has only substance units: false
initial concentration: 8.46311111111111E-23
initial amount: NaN
in compartment: 400538
type: Species

569015
units: 424962
value: 8.1E-14
type: LocalParameter

425023
exponent: 1.0
scale: -6
multipler: 1.0
kind: MOLE
type: SBMLUnit

569092
units: 424962
value: 9.000045E-15
type: LocalParameter

568918
units: 424878
value: 3.75E-16
type: LocalParameter

425740
stoichiometry: 1.0
species: 401157
type: SpeciesReference

434568
stoichiometry: 1.0
species: 403997
type: SpeciesReference

429068
stoichiometry: 1.0
species: 402917
type: SpeciesReference

568994
units: 424878
value: 1.5E-15
type: LocalParameter

430764
stoichiometry: 1.0
species: 401657
type: SpeciesReference

429322
stoichiometry: 1.0
species: 400817
type: SpeciesReference

404557
kinetic law: 425292
product: 425280
reactant: 425268
reactant: 425255
notes: Leslie and Channon BBA 1045 (1990) 261-270 fig6 pp267.
fast: false
reversible: true
type: Reaction

426510
stoichiometry: 1.0
species: 402037
type: SpeciesReference

402797
constant: false
boundary condition: false
has only substance units: false
initial concentration: 1.8
initial amount: NaN
in compartment: 400538
type: Species

403377
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.5
initial amount: NaN
in compartment: 400538
type: Species

568915
units: 424962
value: 6.300045E-15
type: LocalParameter

568802
units: 424878
value: 7.5E-16
type: LocalParameter

400677
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

569099
units: 424962
value: 1.529955E-16
type: LocalParameter

429722
stoichiometry: 1.0
species: 401017
type: SpeciesReference

431776
stoichiometry: 1.0
species: 402097
type: SpeciesReference

433671
stoichiometry: 1.0
species: 403197
type: SpeciesReference

404517
kinetic law: 425194
product: 425182
reactant: 425170
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

427153
stoichiometry: 1.0
species: 402597
type: SpeciesReference

427033
stoichiometry: 1.0
species: 402557
type: SpeciesReference

568955
units: 424962
value: 1.500255E-12
type: LocalParameter

402077
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

426485
local parameters: 568902
local parameters: 568899
notes: kf*Ras_slash_GTP_minus_Ras-kb*Ras_slash_GDP_minus_Ras
type: KineticLaw

407377
kinetic law: 431945
product: 431933
product: 431921
reactant: 431909
fast: false
reversible: false
type: Reaction

568803
units: 424962
value: 1.799955E-17
type: LocalParameter

569246
units: 424962
value: 3.961305E-16
type: LocalParameter

427870
stoichiometry: 1.0
species: 403557
type: SpeciesReference

425963
stoichiometry: 1.0
species: 401217
type: SpeciesReference

569018
units: 424878
value: 4.95E-14
type: LocalParameter

431052
stoichiometry: 1.0
species: 401497
type: SpeciesReference

569249
units: 424878
value: 3.6E-14
type: LocalParameter

429662
stoichiometry: 1.0
species: 400657
type: SpeciesReference

568883
units: 424962
value: 9.000045E-14
type: LocalParameter

568954
units: 424878
value: 7.5E-15
type: LocalParameter

569059
units: 424878
value: 1.5E-16
type: LocalParameter

430388
local parameters: 569157
notes: k3*MAPK_slash_MAPKK_star__slash_MAPKKthr_slash_MAPKKthr_cplx
type: KineticLaw

428318
local parameters: 569058
local parameters: 569055
notes: kf*Gs_minus_alpha*AC_slash_AC2_star_-kb*AC_slash_AC2_star__minus_Gs
type: KineticLaw

569097
units: 424878
value: 6.0E-15
type: LocalParameter

425679
local parameters: 568834
local parameters: 568831
notes: kf*DAG-kb*PLCbeta_slash_PC
type: KineticLaw

434640
stoichiometry: 1.0
species: 404057
type: SpeciesReference

569019
units: 424962
value: 1.1249955E-13
type: LocalParameter

434701
stoichiometry: 1.0
species: 403977
type: SpeciesReference

568995
units: 424914
value: 1.501254E-11
type: LocalParameter

568882
units: 424878
value: 1.5E-15
type: LocalParameter

431800
local parameters: 569213
local parameters: 569212
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

432296
stoichiometry: 1.0
species: 402317
type: SpeciesReference

430509
stoichiometry: 1.0
species: 401597
type: SpeciesReference

404977
kinetic law: 426266
product: 426254
reactant: 426242
reactant: 426230
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

569058
units: 424878
value: 1.5E-15
type: LocalParameter

402937
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

569096
units: 424878
value: 2.4E-14
type: LocalParameter

401457
constant: false
boundary condition: false
has only substance units: false
initial concentration: 3.6
initial amount: NaN
in compartment: 400538
type: Species

402717
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

568914
units: 424878
value: 0.0
type: LocalParameter

427565
stoichiometry: 1.0
species: 403277
type: SpeciesReference

430726
local parameters: 569171
local parameters: 569170
notes: k1*MAPK_slash_MAPKK*MAPK_slash_Raf_star__minus_GTP_minus_Ras-k2*MAPK_slash_Raf_star__minus_GTP_minus_Ras_slash_Raf_star__minus_GTP_minus_Ras_dot_1_slash_Raf_star__minus_GTP_minus_Ras_dot_1_cplx
type: KineticLaw

434265
stoichiometry: 1.0
species: 403777
type: SpeciesReference

568911
units: 424878
value: 1.5E-15
type: LocalParameter

429831
local parameters: 569138
local parameters: 569135
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

568806
units: 424878
value: 1.5E-16
type: LocalParameter

568847
units: 424962
value: 4.499955E-14
type: LocalParameter

426146
stoichiometry: 1.0
species: 401357
type: SpeciesReference

568990
units: 424962
value: 0.0
type: LocalParameter

429431
stoichiometry: 1.0
species: 400877
type: SpeciesReference

434060
stoichiometry: 1.0
species: 404237
type: SpeciesReference

433866
stoichiometry: 1.0
species: 403257
type: SpeciesReference

407897
kinetic law: 433225
product: 433213
product: 433200
reactant: 433188
fast: false
reversible: false
type: Reaction

568807
units: 424962
value: 4.499955E-18
type: LocalParameter

568846
units: 424878
value: 1.5E-15
type: LocalParameter

404297
constant: false
boundary condition: true
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

429552
stoichiometry: 1.0
species: 400917
type: SpeciesReference

427262
stoichiometry: 1.0
species: 402997
type: SpeciesReference

430001
stoichiometry: 1.0
species: 401117
type: SpeciesReference

568887
units: 424962
value: 1.499985E-14
type: LocalParameter

406017
kinetic law: 428608
product: 428596
reactant: 428584
fast: false
reversible: true
type: Reaction

428427
stoichiometry: 1.0
species: 401977
type: SpeciesReference

404117
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: 400538
type: Species

569160
units: 424878
value: 5.25E-16
type: LocalParameter

428716
stoichiometry: 1.0
species: 402037
type: SpeciesReference

568886
units: 424878
value: 1.5E-17
type: LocalParameter

568910
units: 424878
value: 1.5E-15
type: LocalParameter

434496
stoichiometry: 1.0
species: 403877
type: SpeciesReference

431246
stoichiometry: 1.0
species: 401577
type: SpeciesReference

434374
stoichiometry: 1.0
species: 403837
type: SpeciesReference

427723
stoichiometry: 1.0
species: 403237
type: SpeciesReference

433104
stoichiometry: 1.0
species: 402597
type: SpeciesReference

401197
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

403517
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.25
initial amount: NaN
in compartment: 400538
type: Species

568991
units: 424914
value: 5.399946E-15
type: LocalParameter

425364
stoichiometry: 1.0
species: 400777
type: SpeciesReference

426874
stoichiometry: 1.0
species: 402437
type: SpeciesReference

405137
kinetic law: 426608
product: 426596
reactant: 426584
fast: false
reversible: true
type: Reaction

431162
stoichiometry: 1.0
species: 401777
type: SpeciesReference

569091
units: 424878
value: 6.0E-15
type: LocalParameter

403837
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

427347
stoichiometry: 1.0
species: 402917
type: SpeciesReference

427008
local parameters: 568948
local parameters: 568947
notes: kf*Ca*PLC_g_slash_PLC_G_star_-kb*PLC_g_slash_Ca_dot_PLC_g_star_
type: KineticLaw

433757
local parameters: 569294
local parameters: 569293
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

402297
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

429516
stoichiometry: 1.0
species: 400897
type: SpeciesReference

407817
kinetic law: 433032
product: 433020
product: 433008
reactant: 432996
fast: false
reversible: false
type: Reaction

406837
kinetic law: 430630
product: 430618
reactant: 430606
reactant: 430594
notes: Kinetics are the same as for the craf_1* activity, ie., k1=5.5e-6, k2=0.42, k3 = 0.105 These are basedo n Force et al PNAS USA 91 1270-1274, 1994., but k1 is scaled up 5x (ie., Km is scaled down 5x to the value used here and for craf_1* activity: Km = 0.1591).
fast: false
reversible: true
type: Reaction

431306
stoichiometry: 1.0
species: 401837
type: SpeciesReference

569090
units: 424878
value: 2.4E-14
type: LocalParameter

432875
stoichiometry: 1.0
species: 402777
type: SpeciesReference

429020
stoichiometry: 1.0
species: 404297
type: SpeciesReference

402257
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

432368
stoichiometry: 1.0
species: 402337
type: SpeciesReference

427931
stoichiometry: 1.0
species: 403457
type: SpeciesReference

425853
stoichiometry: 1.0
species: 401197
type: SpeciesReference

428536
local parameters: 569078
local parameters: 569075
notes: kf*PKM_slash_Ca_detector*Ca^2-kb*PKM_slash_Ca_dot_detector_complex
type: KineticLaw

406777
kinetic law: 430485
product: 430474
product: 430460
reactant: 430448
fast: false
reversible: false
type: Reaction

430942
stoichiometry: 1.0
species: 401737
type: SpeciesReference

432440
stoichiometry: 1.0
species: 404177
type: SpeciesReference

428137
local parameters: 569042
local parameters: 569039
notes: kf*CaM_minus_Ca4*AC_slash_AC1-kb*AC_slash_AC1_minus_CaM
type: KineticLaw

425630
stoichiometry: 1.0
species: 404137
type: SpeciesReference

405717
kinetic law: 427943
product: 427931
reactant: 427918
reactant: 427906
fast: false
reversible: true
type: Reaction

430400
stoichiometry: 1.0
species: 402657
type: SpeciesReference

431848
local parameters: 569214
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

569010
units: 424878
value: 1.5E-15
type: LocalParameter

433140
stoichiometry: 1.0
species: 402657
type: SpeciesReference

569241
units: 424842
value: 97.2222222222222
type: LocalParameter

427614
stoichiometry: 1.0
species: 403237
type: SpeciesReference

431884
stoichiometry: 1.0
species: 402157
type: SpeciesReference

405177
kinetic law: 426692
product: 426680
reactant: 426668
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

432513
stoichiometry: 1.0
species: 400638
type: SpeciesReference

403877
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

569200
units: 424962
value: 2.97E-16
type: LocalParameter

569011
units: 424962
value: 8.1E-14
type: LocalParameter

428463
stoichiometry: 1.0
species: 403937
type: SpeciesReference

405757
kinetic law: 428039
product: 428027
product: 428015
reactant: 428003
fast: false
reversible: true
type: Reaction

427408
local parameters: 568982
local parameters: 568979
notes: kf*CaM_slash_neurogranin_star_-kb*CaM_slash_neurogranin
type: KineticLaw

401037
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 400538
type: Species

433818
stoichiometry: 1.0
species: 403117
type: SpeciesReference

569201
units: 424878
value: 1.2E-16
type: LocalParameter