449534
units: 443196
value: 1.5E-14
type: LocalParameter

423185
kinetic law: 445323
product: 445311
reactant: 445299
reactant: 445287
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

424765
kinetic law: 449030
product: 449018
product: 449006
reactant: 448994
fast: false
reversible: false
type: Reaction

448581
stoichiometry: 1.0
species: 419566
type: SpeciesReference

445516
stoichiometry: 2.0
species: 421646
type: SpeciesReference

422505
kinetic law: 443754
product: 443742
reactant: 443729
reactant: 443716
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

449635
stoichiometry: 1.0
species: 419886
type: SpeciesReference

423685
kinetic law: 446479
product: 446467
reactant: 446455
notes: Random rate.
fast: false
reversible: true
type: Reaction

449573
units: 443196
value: 8.7E-16
type: LocalParameter

449439
units: 443196
value: 5.4E-14
type: LocalParameter

426365
kinetic law: 453327
product: 453315
reactant: 453303
reactant: 453291
fast: false
reversible: true
type: Reaction

443510
local parameters: 449046
local parameters: 449043
notes: kf*PKC_slash_PKC_minus_Ca_minus_DAG-kb*PKC_slash_PKC_minus_DAG_minus_memb_star_
type: KineticLaw

449533
units: 443196
value: 6.0E-14
type: LocalParameter

423825
kinetic law: 446781
product: 446769
reactant: 446757
fast: false
reversible: true
type: Reaction

446118
stoichiometry: 1.0
species: 421126
type: SpeciesReference

445456
local parameters: 449218
local parameters: 449215
notes: kf*CaMKII_slash_CaMKII_minus_thr286*CaM_minus_Ca4-kb*CaMKII_slash_CaMKII_minus_thr286_star__minus_CaM
type: KineticLaw

448883
local parameters: 449424
local parameters: 449423
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

451366
stoichiometry: 1.0
species: 422305
type: SpeciesReference

447279
stoichiometry: 1.0
species: 422066
type: SpeciesReference

453303
stoichiometry: 1.0
species: 421966
type: SpeciesReference

449574
units: 443280
value: 9.18E-17
type: LocalParameter

449438
units: 443280
value: 9.000045E-15
type: LocalParameter

447968
local parameters: 449389
notes: k3*PLCbeta_slash_PLC_minus_Ca_minus_Gq_slash_PLCb_minus_Ca_minus_Gq_slash_PLCb_minus_Ca_minus_Gq_cplx
type: KineticLaw

449745
stoichiometry: 1.0
species: 419946
type: SpeciesReference

444588
local parameters: 449138
local parameters: 449135
notes: kf*Gq_slash_G_minus_GDP*Gq_slash_mGluR-kb*Gq_slash_Rec_minus_Gq
type: KineticLaw

424126
kinetic law: 447461
product: 447449
product: 447436
reactant: 447424
fast: false
reversible: false
type: Reaction

450071
stoichiometry: 1.0
species: 420126
type: SpeciesReference

420406
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

451222
stoichiometry: 1.0
species: 420806
type: SpeciesReference

446274
stoichiometry: 1.0
species: 419886
type: SpeciesReference

426065
kinetic law: 452593
product: 452581
product: 452569
reactant: 452557
fast: false
reversible: false
type: Reaction

453460
stoichiometry: 1.0
species: 422006
type: SpeciesReference

447533
stoichiometry: 1.0
species: 418826
type: SpeciesReference

450580
stoichiometry: 1.0
species: 420386
type: SpeciesReference

449215
units: 443280
value: 1.500255E-12
type: LocalParameter

421186
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

449571
units: 443280
value: 1.529955E-16
type: LocalParameter

424705
kinetic law: 448883
product: 448871
reactant: 448859
reactant: 448847
notes: Kinetics same as GEF-bg-act-ras
fast: false
reversible: true
type: Reaction

444211
stoichiometry: 1.0
species: 422106
type: SpeciesReference

443571
stoichiometry: 1.0
species: 418606
type: SpeciesReference

448220
stoichiometry: 1.0
species: 419466
type: SpeciesReference

422066
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: 418386
type: Species

421146
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

453051
stoichiometry: 1.0
species: 420706
type: SpeciesReference

452533
stoichiometry: 1.0
species: 421766
type: SpeciesReference

452268
stoichiometry: 1.0
species: 421606
type: SpeciesReference

449214
units: 443196
value: 7.5E-15
type: LocalParameter

444187
local parameters: 449106
local parameters: 449103
notes: kf*Ca*PLCbeta_slash_PLC_minus_Gq-kb*PLCbeta_slash_PLC_minus_Ca_minus_Gq
type: KineticLaw

425485
kinetic law: 451186
product: 451174
product: 451162
reactant: 451150
fast: false
reversible: false
type: Reaction

449572
units: 443196
value: 3.51E-15
type: LocalParameter

444614
stoichiometry: 1.0
species: 422185
type: SpeciesReference

450750
local parameters: 449479
local parameters: 449478
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

452376
stoichiometry: 1.0
species: 421786
type: SpeciesReference

446238
stoichiometry: 1.0
species: 421186
type: SpeciesReference

449683
stoichiometry: 1.0
species: 420846
type: SpeciesReference

449530
units: 443280
value: 3.78E-15
type: LocalParameter

423605
kinetic law: 446298
product: 446286
product: 446274
reactant: 446262
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

419606
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

420166
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

448328
stoichiometry: 1.0
species: 419366
type: SpeciesReference

443946
stoichiometry: 1.0
species: 422126
type: SpeciesReference

443667
stoichiometry: 1.0
species: 422086
type: SpeciesReference

446515
stoichiometry: 1.0
species: 421366
type: SpeciesReference

419646
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

449570
units: 443196
value: 6.0E-15
type: LocalParameter

422625
kinetic law: 444042
product: 444030
reactant: 444018
reactant: 444006
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

448847
stoichiometry: 1.0
species: 419746
type: SpeciesReference

446877
stoichiometry: 2.0
species: 421646
type: SpeciesReference

452967
stoichiometry: 1.0
species: 422325
type: SpeciesReference

453231
local parameters: 449578
local parameters: 449577
notes: k1*AC_slash_AC2*PKC_minus_active-k2*PKC_minus_active_slash_phosph_minus_AC2_slash_phosph_minus_AC2_cplx
type: KineticLaw

444078
stoichiometry: 1.0
species: 418966
type: SpeciesReference

444938
stoichiometry: 1.0
species: 420026
type: SpeciesReference

420566
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

449480
units: 443196
value: 5.25E-16
type: LocalParameter

423165
kinetic law: 445275
product: 445263
reactant: 445250
reactant: 445238
notes: Nice curves from Homma et al JBC 263:14 6592-6598 1988 Fig 5c. The activity falls above 10 uM, but that is too high to reach physiologically anyway, so we\'ll ignore the higher pts and match the lower ones only. Half-max at 1 uM. But Wahl et al JBC 267:15 10447-10456 1992 have half-max at 56 nM which is what I\'ll use.
fast: false
reversible: true
type: Reaction

418546
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0555555555555556
initial amount: NaN
in compartment: 418386
type: Species

449006
stoichiometry: 1.0
species: 419746
type: SpeciesReference

418866
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

449369
units: 443280
value: 4.499955E-14
type: LocalParameter

449219
units: 443196
value: 4.5E-18
type: LocalParameter

425265
kinetic law: 450654
product: 450642
reactant: 450630
reactant: 450618
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

452641
local parameters: 449557
local parameters: 449556
notes: k1*MKP3_slash_MKP3_AA*MKP3_slash_MKP3_synthesis-k2*MKP3_slash_MKP3_synthesis_slash_kenz_slash_kenz_cplx
type: KineticLaw

448774
stoichiometry: 1.0
species: 419646
type: SpeciesReference

447205
stoichiometry: 1.0
species: 418726
type: SpeciesReference

447810
stoichiometry: 1.0
species: 418986
type: SpeciesReference

451977
stoichiometry: 1.0
species: 421486
type: SpeciesReference

453399
stoichiometry: 1.0
species: 422006
type: SpeciesReference

449481
units: 443280
value: 5.147955E-16
type: LocalParameter

448112
local parameters: 449397
local parameters: 449396
notes: k1*MAPK_slash_MAPK_minus_tyr*MAPK_slash_MAPKK_star_-k2*MAPK_slash_MAPKK_star__slash_MAPKKthr_slash_MAPKKthr_cplx
type: KineticLaw

449218
units: 443196
value: 1.5E-16
type: LocalParameter

445564
stoichiometry: 1.0
species: 421646
type: SpeciesReference

453123
local parameters: 449575
local parameters: 449574
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

452158
local parameters: 449539
local parameters: 449538
notes: k1*cAMP*AC_slash_PDE1-k2*AC_slash_PDE1_slash_PDE1_slash_PDE1_cplx
type: KineticLaw

419966
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

447316
local parameters: 449367
local parameters: 449366
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

445142
local parameters: 449190
local parameters: 449187
notes: kf*Sos_slash_Sos_star_*Sos_slash_Grb2-kb*Sos_slash_Sos_star__dot_Grb2
type: KineticLaw

447024
local parameters: 449358
local parameters: 449355
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

424385
kinetic law: 448112
product: 448100
reactant: 448088
reactant: 448076
notes: Rate consts same as for MAPKKtyr.
fast: false
reversible: true
type: Reaction

449367
units: 443196
value: 3.6E-13
type: LocalParameter

451589
stoichiometry: 1.0
species: 420846
type: SpeciesReference

448957
stoichiometry: 1.0
species: 419786
type: SpeciesReference

422925
kinetic law: 444770
product: 444758
reactant: 444746
fast: false
reversible: true
type: Reaction

443304
exponent: -1.0
scale: -6
multipler: 1.0
kind: MOLE
type: SBMLUnit

450169
stoichiometry: 1.0
species: 422166
type: SpeciesReference

443559
local parameters: 449050
local parameters: 449047
notes: kf*PKC_slash_PKC_minus_cytosolic*DAG-kb*PKC_slash_PKC_minus_DAG
type: KineticLaw

446347
local parameters: 449294
local parameters: 449291
notes: kf*PKA_slash_R2C_minus_cAMP4-kb*PKA_minus_active*PKA_slash_R2_minus_cAMP4
type: KineticLaw

449154
units: 443196
value: 0.0
type: LocalParameter

445480
stoichiometry: 1.0
species: 420426
type: SpeciesReference

449368
units: 443196
value: 9.0E-14
type: LocalParameter

445877
stoichiometry: 1.0
species: 421006
type: SpeciesReference

448508
stoichiometry: 1.0
species: 419546
type: SpeciesReference

444974
local parameters: 449174
local parameters: 449171
notes: kf*EGFR_slash_EGFR*EGFR_slash_EGF-kb*EGFR_slash_L_dot_EGFR
type: KineticLaw

419306
constant: false
boundary condition: false
has only substance units: false
initial concentration: 3.6
initial amount: NaN
in compartment: 418386
type: Species

451651
stoichiometry: 1.0
species: 420826
type: SpeciesReference

449963
stoichiometry: 1.0
species: 420066
type: SpeciesReference

448160
local parameters: 449398
notes: k3*MAPK_slash_MAPKK_star__slash_MAPKKthr_slash_MAPKKthr_cplx
type: KineticLaw

447461
local parameters: 449371
notes: k3*PLA2_slash_PLA2_star__minus_Ca_slash_kenz_slash_kenz_cplx
type: KineticLaw

448665
stoichiometry: 1.0
species: 419506
type: SpeciesReference

425885
kinetic law: 452158
product: 452146
reactant: 452134
reactant: 452122
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

446491
stoichiometry: 1.0
species: 421386
type: SpeciesReference

446829
stoichiometry: 1.0
species: 421726
type: SpeciesReference

449151
units: 443196
value: 1.5E-15
type: LocalParameter

453099
stoichiometry: 1.0
species: 422325
type: SpeciesReference

449365
units: 443196
value: 5.4E-14
type: LocalParameter

449579
units: 443196
value: 6.0E-15
type: LocalParameter

448268
stoichiometry: 1.0
species: 419426
type: SpeciesReference

444259
stoichiometry: 1.0
species: 419086
type: SpeciesReference

451186
local parameters: 449495
notes: k3*CaM_po_Ca_pc_n_minus_CaNAB_slash_dephosph_neurogranin_slash_dephosph_neurogranin_cplx
type: KineticLaw

450011
stoichiometry: 1.0
species: 420106
type: SpeciesReference

449062
units: 443196
value: 1.5E-16
type: LocalParameter

450352
stoichiometry: 1.0
species: 420486
type: SpeciesReference

449179
units: 443196
value: 3.0E-18
type: LocalParameter

420766
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

450315
local parameters: 449462
notes: k3*CaMKII_slash_tot_CaM_CaMKII_slash_CaM_act_305_slash_CaM_act_305_cplx
type: KineticLaw

423225
kinetic law: 445408
product: 445395
reactant: 445383
reactant: 445371
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

426005
kinetic law: 452448
product: 452436
reactant: 452424
reactant: 452412
notes: See MKP1-tyr-deph Km is twice as high to avoid saturation.
fast: false
reversible: true
type: Reaction

447920
stoichiometry: 1.0
species: 419026
type: SpeciesReference

449366
units: 443280
value: 2.250045E-14
type: LocalParameter

425545
kinetic law: 451330
product: 451318
reactant: 451306
reactant: 451294
fast: false
reversible: true
type: Reaction

422785
kinetic law: 444422
product: 444409
reactant: 444396
reactant: 444383
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

452605
stoichiometry: 1.0
species: 422245
type: SpeciesReference

449063
units: 443280
value: 4.499955E-18
type: LocalParameter

450969
stoichiometry: 1.0
species: 420446
type: SpeciesReference

452448
local parameters: 449551
local parameters: 449548
notes: k1*MAPK_star_*MKP3_slash_MKP_minus_3-k2*MKP3_slash_MKP_minus_3_slash_MKP3_minus_thr_minus_deph_slash_MKP3_minus_thr_minus_deph_cplx
type: KineticLaw

446685
stoichiometry: 1.0
species: 419966
type: SpeciesReference

451615
stoichiometry: 1.0
species: 420986
type: SpeciesReference

451820
local parameters: 449521
local parameters: 449518
notes: kcat*AC_slash_AC2_minus_Gs*AC_slash_ATP/(Km+AC_slash_ATP)
type: KineticLaw

449927
stoichiometry: 1.0
species: 420046
type: SpeciesReference

450642
stoichiometry: 1.0
species: 420566
type: SpeciesReference

449891
stoichiometry: 1.0
species: 419986
type: SpeciesReference

446600
stoichiometry: 1.0
species: 421346
type: SpeciesReference

446009
local parameters: 449266
local parameters: 449263
notes: kf*CaM_minus_Ca3*CaNAB_minus_Ca4-kb*PP2B_slash_CaMCa3_minus_CaNAB
type: KineticLaw

445985
stoichiometry: 1.0
species: 420966
type: SpeciesReference

449577
units: 443280
value: 9.000045E-16
type: LocalParameter

449363
units: 443280
value: 1.35E-14
type: LocalParameter

452689
local parameters: 449558
notes: k3*MKP3_slash_MKP3_synthesis_slash_kenz_slash_kenz_cplx
type: KineticLaw

447169
local parameters: 449362
notes: k3*PLA2_slash_PIP2_minus_PLA2_star__slash_kenz_slash_kenz_cplx
type: KineticLaw

445226
local parameters: 449198
local parameters: 449195
notes: kf*Sos_slash_Grb2*Sos_slash_Sos-kb*Sos_slash_Sos_dot_Grb2
type: KineticLaw

446937
local parameters: 449350
local parameters: 449347
notes: kf*PKC_slash_PKM_minus_zeta-kb*PKM_slash_degraded_PKM
type: KineticLaw

449263
units: 443280
value: 3.357045E-15
type: LocalParameter

425505
kinetic law: 451234
product: 451222
reactant: 451210
reactant: 451198
fast: false
reversible: true
type: Reaction

453412
stoichiometry: 1.0
species: 422026
type: SpeciesReference

421766
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

449578
units: 443196
value: 2.4E-14
type: LocalParameter

419746
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.5
initial amount: NaN
in compartment: 418386
type: Species

449150
units: 443196
value: 1.5E-15
type: LocalParameter

449364
units: 443196
value: 2.16E-13
type: LocalParameter

445829
stoichiometry: 2.0
species: 421646
type: SpeciesReference

449262
units: 443196
value: 1.5E-15
type: LocalParameter

422545
kinetic law: 443838
product: 443826
reactant: 443814
reactant: 443802
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

449575
units: 443196
value: 2.1E-15
type: LocalParameter

449818
stoichiometry: 1.0
species: 419746
type: SpeciesReference

447424
stoichiometry: 1.0
species: 418806
type: SpeciesReference

446383
stoichiometry: 1.0
species: 421266
type: SpeciesReference

453351
stoichiometry: 1.0
species: 418546
type: SpeciesReference

424425
kinetic law: 448208
product: 448196
reactant: 448184
reactant: 448172
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

449361
units: 443196
value: 6.624E-14
type: LocalParameter

449211
units: 443280
value: 7.499925E-14
type: LocalParameter

448919
stoichiometry: 1.0
species: 419686
type: SpeciesReference

447859
local parameters: 449386
notes: k3*PLCbeta_slash_PLC_minus_Ca_slash_PLC_minus_Ca_slash_PLC_minus_Ca_cplx
type: KineticLaw

449066
units: 443196
value: 6.0E-15
type: LocalParameter

450424
stoichiometry: 1.0
species: 420426
type: SpeciesReference

451054
stoichiometry: 1.0
species: 420646
type: SpeciesReference

421826
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

419466
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

424025
kinetic law: 447217
product: 447205
reactant: 447193
reactant: 447181
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

449576
units: 443196
value: 5.25E-16
type: LocalParameter

450690
stoichiometry: 1.0
species: 420546
type: SpeciesReference

449362
units: 443196
value: 1.656E-14
type: LocalParameter

448994
stoichiometry: 1.0
species: 419806
type: SpeciesReference

444030
stoichiometry: 1.0
species: 419006
type: SpeciesReference

449210
units: 443196
value: 0.0
type: LocalParameter

423445
kinetic law: 445913
product: 445901
reactant: 445889
reactant: 445877
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

418486
constant: false
boundary condition: false
has only substance units: false
initial concentration: 8.46311111111111E-23
initial amount: NaN
in compartment: 418386
type: Species

452484
stoichiometry: 1.0
species: 421726
type: SpeciesReference

443462
stoichiometry: 1.0
species: 418446
type: SpeciesReference

421366
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

449260
stoichiometry: 1.0
species: 419866
type: SpeciesReference

424465
kinetic law: 448304
product: 448292
reactant: 448280
reactant: 448268
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

449067
units: 443196
value: 6.0E-16
type: LocalParameter

449186
units: 443196
value: 1.5E-16
type: LocalParameter

449254
units: 443196
value: 1.5E-15
type: LocalParameter

452798
stoichiometry: 1.0
species: 419786
type: SpeciesReference

421586
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

444539
local parameters: 449134
local parameters: 449131
notes: kf*Gq_slash_Rec_minus_Glu_minus_Gq-kb*G_star_GTP*BetaGamma*Gq_slash_Rec_minus_Glu
type: KineticLaw

449479
units: 443196
value: 2.1E-15
type: LocalParameter

443838
local parameters: 449074
local parameters: 449071
notes: kf*PLA2_slash_PLA2_star_*Ca-kb*PLA2_slash_PLA2_star__minus_Ca
type: KineticLaw

444474
local parameters: 449130
local parameters: 449127
notes: kf*Glu*Gq_slash_Rec_minus_Gq-kb*Gq_slash_Rec_minus_Glu_minus_Gq
type: KineticLaw

451486
stoichiometry: 1.0
species: 420866
type: SpeciesReference

450921
stoichiometry: 1.0
species: 420546
type: SpeciesReference

452919
stoichiometry: 1.0
species: 421866
type: SpeciesReference

449255
units: 443232
value: 1.501254E-11
type: LocalParameter

449478
units: 443280
value: 5.147955E-16
type: LocalParameter

447242
stoichiometry: 1.0
species: 418586
type: SpeciesReference

418906
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

445263
stoichiometry: 1.0
species: 420306
type: SpeciesReference

450242
stoichiometry: 1.0
species: 422285
type: SpeciesReference

449371
units: 443196
value: 1.8E-13
type: LocalParameter

421286
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

443874
local parameters: 449078
local parameters: 449075
notes: kf*PLA2_slash_PLA2_star_-kb*PLA2_slash_PLA2_minus_cytosolic
type: KineticLaw

419166
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

444422
local parameters: 449126
local parameters: 449123
notes: kf*Gq_slash_G_minus_GDP*Gq_slash_Rec_minus_Glu-kb*Gq_slash_Rec_minus_Glu_minus_Gq
type: KineticLaw

449107
units: 443280
value: 2.520045E-14
type: LocalParameter

449059
units: 443280
value: 1.799955E-17
type: LocalParameter

449370
units: 443196
value: 7.2E-13
type: LocalParameter

453003
stoichiometry: 1.0
species: 422325
type: SpeciesReference

422885
kinetic law: 444686
product: 444674
reactant: 444662
reactant: 444650
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

445937
stoichiometry: 1.0
species: 420766
type: SpeciesReference

426325
kinetic law: 453231
product: 453219
reactant: 453207
reactant: 453195
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

422845
kinetic law: 444588
product: 444576
reactant: 444564
reactant: 444552
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

425445
kinetic law: 451090
product: 451078
product: 451066
reactant: 451054
fast: false
reversible: false
type: Reaction

449058
units: 443196
value: 7.5E-16
type: LocalParameter

449183
units: 443280
value: 7.499655E-16
type: LocalParameter

451102
stoichiometry: 1.0
species: 420706
type: SpeciesReference

449708
local parameters: 449440
notes: k3*PKA_minus_active_slash_PKA_minus_phosph_minus_I1_slash_PKA_minus_phosph_minus_I1_cplx
type: KineticLaw

423865
kinetic law: 446853
product: 446841
reactant: 446829
fast: false
reversible: true
type: Reaction

421206
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

447702
local parameters: 449382
local parameters: 449381
notes: k1*Sos_slash_Sos*MAPK_star_-k2*MAPK_star__slash_phosph_Sos_slash_phosph_Sos_cplx
type: KineticLaw

446985
stoichiometry: 1.0
species: 422066
type: SpeciesReference

446563
stoichiometry: 1.0
species: 421406
type: SpeciesReference

450861
stoichiometry: 1.0
species: 420606
type: SpeciesReference

451929
stoichiometry: 1.0
species: 421286
type: SpeciesReference

419126
constant: false
boundary condition: false
has only substance units: false
initial concentration: 1.0
initial amount: NaN
in compartment: 418386
type: Species

452822
stoichiometry: 1.0
species: 421846
type: SpeciesReference

422026
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

424165
kinetic law: 447557
product: 447545
product: 447533
reactant: 447521
fast: false
reversible: false
type: Reaction

449147
units: 443280
value: 9.000045E-15
type: LocalParameter

449258
units: 443196
value: 1.5E-15
type: LocalParameter

447072
local parameters: 449359
notes: k3*PLA2_slash_PLA2_minus_Ca_star__slash_kenz_slash_kenz_cplx
type: KineticLaw

445769
local parameters: 449246
local parameters: 449243
notes: kf*PP1_slash_I1_star_*PP1_minus_active-kb*PP1_slash_PP1_minus_I1_star_
type: KineticLaw

445106
stoichiometry: 1.0
species: 420226
type: SpeciesReference

445070
stoichiometry: 1.0
species: 420126
type: SpeciesReference

425625
kinetic law: 451523
product: 451510
reactant: 451498
reactant: 451486
notes: k1 changed from 3.3e-6 to 6.6e-6
fast: false
reversible: true
type: Reaction

443401
stoichiometry: 1.0
species: 418566
type: SpeciesReference

452110
local parameters: 449537
notes: k3*AC_slash_cAMP_minus_PDE_star__slash_PDE_star__slash_PDE_star__cplx
type: KineticLaw

444320
stoichiometry: 1.0
species: 419126
type: SpeciesReference

449146
units: 443196
value: 7.5E-16
type: LocalParameter

449259
units: 443280
value: 3.600045E-16
type: LocalParameter

449106
units: 443196
value: 1.5E-15
type: LocalParameter

420986
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

425225
kinetic law: 450556
product: 450544
reactant: 450532
reactant: 450520
fast: false
reversible: true
type: Reaction

445371
stoichiometry: 1.0
species: 419966
type: SpeciesReference

450132
stoichiometry: 1.0
species: 418926
type: SpeciesReference

446154
local parameters: 449278
local parameters: 449275
notes: kf*PKA_slash_R2C2_minus_cAMP*cAMP-kb*PKA_slash_R2C2_minus_cAMP2
type: KineticLaw

450544
stoichiometry: 1.0
species: 420526
type: SpeciesReference

424605
kinetic law: 448641
product: 448629
product: 448617
reactant: 448605
fast: false
reversible: false
type: Reaction

444139
local parameters: 449102
local parameters: 449099
notes: kf*PLCbeta_slash_PLC*G_star_GTP-kb*PLCbeta_slash_PLC_minus_Gq
type: KineticLaw

418506
constant: false
boundary condition: false
has only substance units: false
initial concentration: 1.161E-16
initial amount: NaN
in compartment: 418386
type: Species

425665
kinetic law: 451627
product: 451615
reactant: 451602
reactant: 451589
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

448064
local parameters: 449395
notes: k3*MAPK_slash_MAPKK_star__slash_MAPKKtyr_slash_MAPKKtyr_cplx
type: KineticLaw

444662
stoichiometry: 1.0
species: 419726
type: SpeciesReference

447120
local parameters: 449361
local parameters: 449360
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

420906
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.12
initial amount: NaN
in compartment: 418386
type: Species

424965
kinetic law: 449903
product: 449891
product: 449879
reactant: 449866
fast: false
reversible: false
type: Reaction

449103
units: 443280
value: 4.499955E-14
type: LocalParameter

425585
kinetic law: 451426
product: 451414
reactant: 451402
reactant: 451390
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

445408
local parameters: 449214
local parameters: 449211
notes: kf*CaM_minus_Ca4*CaMKII_slash_CaMKII-kb*CaMKII_slash_CaMKII_minus_CaM
type: KineticLaw

443244
exponent: 3.0
scale: 0
multipler: 1.0
kind: LITRE
type: SBMLUnit

452713
stoichiometry: 1.0
species: 422325
type: SpeciesReference

449794
stoichiometry: 1.0
species: 419886
type: SpeciesReference

449187
units: 443280
value: 3.75003E-17
type: LocalParameter

451724
local parameters: 449515
local parameters: 449514
notes: kcat*AC_slash_AC1_minus_CaM*AC_slash_ATP/(Km+AC_slash_ATP)
type: KineticLaw

447653
local parameters: 449380
notes: k3*MAPK_star__slash_MAPK_star__minus_feedback_slash_MAPK_star__minus_feedback_cplx
type: KineticLaw

449782
stoichiometry: 1.0
species: 421506
type: SpeciesReference

449143
units: 443280
value: 1.499985E-14
type: LocalParameter

420946
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

423126
kinetic law: 445178
product: 445166
reactant: 445154
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

444710
stoichiometry: 1.0
species: 419666
type: SpeciesReference

449430
units: 443196
value: 6.0E-14
type: LocalParameter

448810
stoichiometry: 1.0
species: 419726
type: SpeciesReference

419246
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.5
initial amount: NaN
in compartment: 418386
type: Species

420006
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

453159
stoichiometry: 1.0
species: 420706
type: SpeciesReference

450702
local parameters: 449477
notes: k3*PP1_minus_active_slash_Deph_minus_thr286_slash_Deph_minus_thr286_cplx
type: KineticLaw

420306
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

420666
constant: false
boundary condition: false
has only substance units: false
initial concentration: 20.0
initial amount: NaN
in compartment: 418386
type: Species

419926
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

424925
kinetic law: 449806
product: 449794
product: 449782
reactant: 449770
fast: false
reversible: false
type: Reaction

449471
units: 443196
value: 7.5E-16
type: LocalParameter

422386
kinetic law: 443389
product: 443377
reactant: 443365
reactant: 443353
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

449515
units: 443160
value: 20.0
type: LocalParameter

451549
stoichiometry: 1.0
species: 420886
type: SpeciesReference

423765
kinetic law: 446660
product: 446648
reactant: 446636
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

449326
units: 443196
value: 7.5E-15
type: LocalParameter

449431
units: 443196
value: 1.5E-14
type: LocalParameter

451018
stoichiometry: 1.0
species: 420546
type: SpeciesReference

446769
stoichiometry: 1.0
species: 421686
type: SpeciesReference

424205
kinetic law: 447653
product: 447641
product: 447629
reactant: 447617
fast: false
reversible: false
type: Reaction

446045
stoichiometry: 1.0
species: 421086
type: SpeciesReference

443982
stoichiometry: 1.0
species: 422146
type: SpeciesReference

448436
stoichiometry: 1.0
species: 419506
type: SpeciesReference

425845
kinetic law: 452062
product: 452050
reactant: 452037
reactant: 452025
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

449102
units: 443196
value: 1.5E-15
type: LocalParameter

445660
stoichiometry: 1.0
species: 420666
type: SpeciesReference

449470
units: 443196
value: 3.0E-15
type: LocalParameter

419206
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

443910
stoichiometry: 1.0
species: 418966
type: SpeciesReference

449516
units: 443196
value: 1.05E-14
type: LocalParameter

420626
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

420686
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

420346
constant: false
boundary condition: false
has only substance units: false
initial concentration: 70.0
initial amount: NaN
in compartment: 418386
type: Species

448376
stoichiometry: 1.0
species: 419506
type: SpeciesReference

449518
units: 443196
value: 2.7E-14
type: LocalParameter

444770
local parameters: 449154
local parameters: 449151
notes: kf*Ras_slash_GEF_star_-kb*Ras_slash_inact_minus_GEF
type: KineticLaw

420726
constant: false
boundary condition: false
has only substance units: false
initial concentration: 10.0
initial amount: NaN
in compartment: 418386
type: Species

450460
local parameters: 449467
local parameters: 449466
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

449432
units: 443280
value: 2.97E-16
type: LocalParameter

450654
local parameters: 449476
local parameters: 449473
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

423265
kinetic law: 445492
product: 445480
reactant: 445468
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

445034
stoichiometry: 1.0
species: 420146
type: SpeciesReference

443353
stoichiometry: 1.0
species: 418526
type: SpeciesReference

449473
units: 443280
value: 5.147955E-16
type: LocalParameter

426145
kinetic law: 452786
product: 452774
product: 452762
reactant: 452750
fast: false
reversible: false
type: Reaction

449539
units: 443196
value: 1.0005E-14
type: LocalParameter

419286
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.5
initial amount: NaN
in compartment: 418386
type: Species

449517
units: 443160
value: 20.1152893440692
type: LocalParameter

452750
stoichiometry: 1.0
species: 421826
type: SpeciesReference

426105
kinetic law: 452689
product: 452677
product: 452665
reactant: 452653
fast: false
reversible: false
type: Reaction

447762
stoichiometry: 1.0
species: 422166
type: SpeciesReference

449433
units: 443196
value: 1.2E-16
type: LocalParameter

446503
stoichiometry: 1.0
species: 421626
type: SpeciesReference

448016
local parameters: 449394
local parameters: 449391
notes: k1*MAPK_slash_MAPK*MAPK_slash_MAPKK_star_-k2*MAPK_slash_MAPKK_star__slash_MAPKKtyr_slash_MAPKKtyr_cplx
type: KineticLaw

449327
units: 443196
value: 1.5E-13
type: LocalParameter

443729
stoichiometry: 1.0
species: 418626
type: SpeciesReference

423485
kinetic law: 446009
product: 445997
reactant: 445985
reactant: 445973
fast: false
reversible: true
type: Reaction

448629
stoichiometry: 1.0
species: 419506
type: SpeciesReference

449434
units: 443196
value: 3.0E-17
type: LocalParameter

449182
units: 443196
value: 4.95E-19
type: LocalParameter

444866
stoichiometry: 1.0
species: 419966
type: SpeciesReference

420286
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

424065
kinetic law: 447316
product: 447304
reactant: 447291
reactant: 447279
notes: 10 X raise oct 22 12 X raise oct 24 + conversion to k2 =4 * k3
fast: false
reversible: true
type: Reaction

447352
stoichiometry: 1.0
species: 418746
type: SpeciesReference

444284
local parameters: 449114
local parameters: 449111
notes: kf*Gq_slash_G_minus_GDP-kb*G_star_GTP*BetaGamma
type: KineticLaw

449537
units: 443196
value: 3.0E-14
type: LocalParameter

449322
units: 443196
value: 0.0
type: LocalParameter

418386
constant: true
size: 1.5E-15
spatial dimensions: 3.0
type: Compartment

445347
stoichiometry: 1.0
species: 420306
type: SpeciesReference

449435
units: 443280
value: 9.000045E-15
type: LocalParameter

448484
stoichiometry: 1.0
species: 419546
type: SpeciesReference

446081
stoichiometry: 1.0
species: 421286
type: SpeciesReference

449512
units: 443196
value: 2.04E-16
type: LocalParameter

449538
units: 443280
value: 3.149955E-16
type: LocalParameter

443766
stoichiometry: 1.0
species: 418586
type: SpeciesReference

445720
local parameters: 449242
local parameters: 449239
notes: kf*CaM_slash_neurogranin_star_-kb*CaM_slash_neurogranin
type: KineticLaw

449321
local parameters: 449434
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

452037
stoichiometry: 1.0
species: 421506
type: SpeciesReference

449436
units: 443196
value: 5.4E-14
type: LocalParameter

422445
kinetic law: 443607
product: 443595
reactant: 443583
reactant: 443571
notes: Leslie and Channon BBA 1045 (1990) 261-270 fig6 pp267.
fast: false
reversible: true
type: Reaction

423065
kinetic law: 445046
product: 445034
reactant: 445022
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

426185
kinetic law: 452883
product: 452871
product: 452858
reactant: 452846
fast: false
reversible: false
type: Reaction

449854
local parameters: 449448
local parameters: 449445
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

449477
units: 443196
value: 5.25E-16
type: LocalParameter

449513
units: 443196
value: 5.1E-17
type: LocalParameter

421426
constant: false
boundary condition: false
has only substance units: false
initial concentration: 325493.333333333
initial amount: NaN
in compartment: 418406
type: Species

446455
stoichiometry: 1.0
species: 421346
type: SpeciesReference

419706
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

451402
stoichiometry: 1.0
species: 420906
type: SpeciesReference

449535
units: 443280
value: 7.56E-15
type: LocalParameter

452569
stoichiometry: 1.0
species: 419306
type: SpeciesReference

420086
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

451258
stoichiometry: 1.0
species: 420826
type: SpeciesReference

444758
stoichiometry: 1.0
species: 419666
type: SpeciesReference

418946
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.8
initial amount: NaN
in compartment: 418386
type: Species

450811
stoichiometry: 1.0
species: 420446
type: SpeciesReference

449437
units: 443196
value: 1.35E-14
type: LocalParameter

451330
local parameters: 449500
local parameters: 449499
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

445612
stoichiometry: 1.0
species: 421646
type: SpeciesReference

449323
units: 443280
value: 1.08E-12
type: LocalParameter

421866
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

449514
units: 443196
value: 2.7E-14
type: LocalParameter

449476
units: 443196
value: 2.1E-15
type: LocalParameter

449536
units: 443196
value: 1.2E-13
type: LocalParameter

418826
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

449522
units: 443196
value: 2.7E-14
type: LocalParameter

451210
stoichiometry: 1.0
species: 422305
type: SpeciesReference

444576
stoichiometry: 1.0
species: 419186
type: SpeciesReference

449544
units: 443280
value: 7.50006E-18
type: LocalParameter

449733
stoichiometry: 1.0
species: 419886
type: SpeciesReference

419066
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

420506
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

449203
units: 443280
value: 1.799955E-14
type: LocalParameter

447545
stoichiometry: 1.0
species: 418846
type: SpeciesReference

425745
kinetic law: 451820
modifier: 451808
product: 451796
reactant: 451784
fast: false
reversible: false
type: Reaction

446262
stoichiometry: 1.0
species: 421186
type: SpeciesReference

453472
local parameters: 449588
notes: k3*PKM_slash_Ca_dot_detector_complex_slash_kenz_slash_kenz_cplx
type: KineticLaw

449099
units: 443280
value: 3.78E-15
type: LocalParameter

452255
local parameters: 449542
local parameters: 449541
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

448232
stoichiometry: 1.0
species: 419426
type: SpeciesReference

449521
units: 443160
value: 20.0
type: LocalParameter

443583
stoichiometry: 1.0
species: 421646
type: SpeciesReference

449543
units: 443196
value: 1.5E-14
type: LocalParameter

449202
units: 443196
value: 1.5E-14
type: LocalParameter

449584
units: 443280
value: 2.99997E-16
type: LocalParameter

444175
stoichiometry: 1.0
species: 419006
type: SpeciesReference

444626
stoichiometry: 1.0
species: 419226
type: SpeciesReference

452521
stoichiometry: 1.0
species: 421726
type: SpeciesReference

449098
units: 443280
value: 0.0
type: LocalParameter

450593
stoichiometry: 1.0
species: 422286
type: SpeciesReference

444818
stoichiometry: 1.0
species: 419766
type: SpeciesReference

449546
units: 443196
value: 6.0E-18
type: LocalParameter

426425
kinetic law: 453472
product: 453460
product: 453448
reactant: 453436
fast: false
reversible: false
type: Reaction

449427
units: 443280
value: 7.42284E-14
type: LocalParameter

425385
kinetic law: 450945
product: 450933
reactant: 450921
reactant: 450909
fast: false
reversible: true
type: Reaction

445504
stoichiometry: 1.0
species: 420666
type: SpeciesReference

449623
stoichiometry: 1.0
species: 420826
type: SpeciesReference

449294
units: 443280
value: 2.7E-14
type: LocalParameter

445444
stoichiometry: 1.0
species: 420386
type: SpeciesReference

449545
units: 443196
value: 2.4E-17
type: LocalParameter

425345
kinetic law: 450849
product: 450836
reactant: 450824
reactant: 450811
notes: See Cohen et al
fast: false
reversible: true
type: Reaction

450496
stoichiometry: 1.0
species: 422286
type: SpeciesReference

453315
stoichiometry: 1.0
species: 421986
type: SpeciesReference

443292
exponent: 2.0
scale: 0
multipler: 1.0
kind: LITRE
type: SBMLUnit

448895
stoichiometry: 1.0
species: 419706
type: SpeciesReference

445841
stoichiometry: 1.0
species: 421026
type: SpeciesReference

451378
local parameters: 449501
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

447267
local parameters: 449365
notes: k3*PLA2_slash_PIP2_minus_Ca_minus_PLA2_star__slash_kenz_slash_kenz_cplx
type: KineticLaw

449295
units: 443280
value: 9.000045E-14
type: LocalParameter

450849
local parameters: 449482
local parameters: 449481
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

449398
units: 443196
value: 4.5E-16
type: LocalParameter

452328
stoichiometry: 1.0
species: 421686
type: SpeciesReference

449540
units: 443196
value: 2.5005E-15
type: LocalParameter

449319
units: 443196
value: 1.5E-16
type: LocalParameter

444066
stoichiometry: 1.0
species: 419106
type: SpeciesReference

444926
local parameters: 449170
local parameters: 449167
notes: kf*Ras_slash_inact_minus_GEF_star_-kb*Ras_slash_inact_minus_GEF
type: KineticLaw

449296
stoichiometry: 1.0
species: 419726
type: SpeciesReference

448786
local parameters: 449421
local parameters: 449420
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

425425
kinetic law: 451042
product: 451030
reactant: 451018
reactant: 451006
fast: false
reversible: true
type: Reaction

422665
kinetic law: 444139
product: 444127
reactant: 444115
reactant: 444103
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

423745
kinetic law: 446624
product: 446612
reactant: 446600
reactant: 446588
notes: kb/kf = 1.2 nM so kf = kb/720 = 1.3888 * kb.
fast: false
reversible: true
type: Reaction

447217
local parameters: 449364
local parameters: 449363
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

449018
stoichiometry: 1.0
species: 419786
type: SpeciesReference

422725
kinetic law: 444284
product: 444271
product: 444259
reactant: 444247
notes: kf = kg1 = 0.01/sec, kb = 0. This is the basal exchange of GTP for GDP.
fast: false
reversible: true
type: Reaction

421966
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.00555555555555556
initial amount: NaN
in compartment: 418386
type: Species

419886
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

449207
units: 443196
value: 7.5E-17
type: LocalParameter

449357
stoichiometry: 1.0
species: 419906
type: SpeciesReference

451510
stoichiometry: 1.0
species: 420946
type: SpeciesReference

419566
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

449397
units: 443196
value: 1.8E-15
type: LocalParameter

422106
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: 418386
type: Species

423705
kinetic law: 446527
product: 446515
reactant: 446503
reactant: 446491
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

420426
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

451965
local parameters: 449533
local parameters: 449530
notes: k1*cAMP*AC_slash_cAMP_minus_PDE-k2*AC_slash_cAMP_minus_PDE_slash_PDE_slash_PDE_cplx
type: KineticLaw

446745
local parameters: 449330
local parameters: 449327
notes: kf*Ca_input-kb*Ca
type: KineticLaw

422146
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: 418406
type: Species

447822
stoichiometry: 1.0
species: 418566
type: SpeciesReference

448124
stoichiometry: 1.0
species: 419406
type: SpeciesReference

449206
units: 443196
value: 1.5E-14
type: LocalParameter

449358
units: 443196
value: 3.24E-14
type: LocalParameter

445552
stoichiometry: 1.0
species: 420766
type: SpeciesReference

453207
stoichiometry: 1.0
species: 422325
type: SpeciesReference

449580
units: 443280
value: 3.75003E-17
type: LocalParameter

450508
local parameters: 449468
notes: k3*CaMKII_slash_tot_autonomous_CaMKII_slash_auton_305_slash_auton_305_cplx
type: KineticLaw

421246
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.25
initial amount: NaN
in compartment: 418386
type: Species

452364
stoichiometry: 1.0
species: 421706
type: SpeciesReference

450388
stoichiometry: 1.0
species: 420386
type: SpeciesReference

447581
stoichiometry: 1.0
species: 418846
type: SpeciesReference

449542
units: 443196
value: 6.0E-14
type: LocalParameter

446226
stoichiometry: 1.0
species: 421166
type: SpeciesReference

449298
units: 443196
value: 1.5E-15
type: LocalParameter

422185
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: 418386
type: Species

443958
local parameters: 449086
local parameters: 449083
notes: kf*IP3-kb*PLCbeta_slash_Inositol
type: KineticLaw

448316
stoichiometry: 1.0
species: 419486
type: SpeciesReference

424645
kinetic law: 448738
product: 448726
product: 448714
reactant: 448702
fast: false
reversible: false
type: Reaction

449359
units: 443196
value: 8.1E-15
type: LocalParameter

449581
units: 443196
value: 3.0E-16
type: LocalParameter

420466
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

446527
local parameters: 449310
local parameters: 449307
notes: kf*AC_slash_AC2*Gs_minus_alpha-kb*AC_slash_AC2_minus_Gs
type: KineticLaw

449399
units: 443280
value: 1.41426E-14
type: LocalParameter

449541
units: 443280
value: 1.89E-15
type: LocalParameter

443655
local parameters: 449058
local parameters: 449055
notes: kf*temp_minus_PIP2*PLA2_slash_PLA2_minus_cytosolic-kb*PLA2_slash_PIP2_minus_PLA2_star_
type: KineticLaw

452050
stoichiometry: 1.0
species: 421526
type: SpeciesReference

443208
exponent: 1.0
scale: 0
multipler: 1.0
kind: LITRE
type: SBMLUnit

449318
units: 443196
value: 1.5E-15
type: LocalParameter

419806
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

420366
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

453243
stoichiometry: 1.0
species: 421926
type: SpeciesReference

449299
units: 443280
value: 7.499925E-14
type: LocalParameter

453195
stoichiometry: 1.0
species: 421386
type: SpeciesReference

451438
stoichiometry: 1.0
species: 420926
type: SpeciesReference

448859
stoichiometry: 1.0
species: 419686
type: SpeciesReference

449582
units: 443196
value: 7.5E-17
type: LocalParameter

446865
stoichiometry: 1.0
species: 421946
type: SpeciesReference

452979
local parameters: 449570
notes: k3*PKC_minus_active_slash_PKC_minus_act_minus_GEF_slash_PKC_minus_act_minus_GEF_cplx
type: KineticLaw

422186
constant: true
boundary condition: true
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

451270
stoichiometry: 1.0
species: 422305
type: SpeciesReference

449050
units: 443196
value: 1.5E-16
type: LocalParameter

450023
stoichiometry: 1.0
species: 420046
type: SpeciesReference

451198
stoichiometry: 1.0
species: 420846
type: SpeciesReference

446817
local parameters: 449338
local parameters: 449335
notes: kf*MKP3_slash_nucleotides-kb*MKP3_slash_MKP3_synthesis
type: KineticLaw

453087
stoichiometry: 1.0
species: 420686
type: SpeciesReference

444247
stoichiometry: 1.0
species: 419126
type: SpeciesReference

450303
stoichiometry: 1.0
species: 422285
type: SpeciesReference

447932
stoichiometry: 1.0
species: 418566
type: SpeciesReference

449091
units: 443280
value: 3.78E-14
type: LocalParameter

419386
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

450340
stoichiometry: 1.0
species: 422285
type: SpeciesReference

419546
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

423565
kinetic law: 446202
product: 446190
reactant: 446178
reactant: 446166
fast: false
reversible: true
type: Reaction

449354
units: 443196
value: 0.0
type: LocalParameter

424585
kinetic law: 448593
product: 448581
reactant: 448568
reactant: 448556
fast: false
reversible: true
type: Reaction

420046
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

419506
constant: false
boundary condition: false
has only substance units: false
initial concentration: 1.0
initial amount: NaN
in compartment: 418386
type: Species

449696
stoichiometry: 1.0
species: 419886
type: SpeciesReference

446697
stoichiometry: 1.0
species: 421586
type: SpeciesReference

449915
stoichiometry: 1.0
species: 420306
type: SpeciesReference

449090
units: 443196
value: 0.0
type: LocalParameter

424985
kinetic law: 449951
product: 449939
reactant: 449927
reactant: 449915
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

422485
kinetic law: 443704
product: 443691
reactant: 443679
reactant: 443667
fast: false
reversible: true
type: Reaction

450630
stoichiometry: 1.0
species: 420546
type: SpeciesReference

449051
units: 443280
value: 1.499985E-15
type: LocalParameter

450957
stoichiometry: 1.0
species: 420626
type: SpeciesReference

452436
stoichiometry: 1.0
species: 421746
type: SpeciesReference

451627
local parameters: 449512
local parameters: 449509
notes: k1*PP1_slash_I1_star_*CaNAB_minus_Ca4-k2*CaNAB_minus_Ca4_slash_dephosph_inhib1_noCaM_slash_dephosph_inhib1_noCaM_cplx
type: KineticLaw

448969
stoichiometry: 1.0
species: 419806
type: SpeciesReference

445130
stoichiometry: 1.0
species: 420166
type: SpeciesReference

447328
stoichiometry: 1.0
species: 418766
type: SpeciesReference

453135
stoichiometry: 1.0
species: 421906
type: SpeciesReference

447036
stoichiometry: 1.0
species: 418646
type: SpeciesReference

449355
units: 443280
value: 2.025E-15
type: LocalParameter

444308
stoichiometry: 1.0
species: 419066
type: SpeciesReference

443316
exponent: -1.0
scale: 0
multipler: 1.0
kind: SECOND
type: SBMLUnit

425805
kinetic law: 451965
product: 451953
reactant: 451941
reactant: 451929
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

446335
stoichiometry: 1.0
species: 421226
type: SpeciesReference

443547
stoichiometry: 1.0
species: 418506
type: SpeciesReference

446069
stoichiometry: 1.0
species: 421106
type: SpeciesReference

425165
kinetic law: 450412
product: 450400
product: 450388
reactant: 450376
fast: false
reversible: false
type: Reaction

445889
stoichiometry: 2.0
species: 421646
type: SpeciesReference

448678
stoichiometry: 1.0
species: 419586
type: SpeciesReference

445492
local parameters: 449222
local parameters: 449219
notes: kf*CaMKII_slash_CaMKII-kb*CaMKII_slash_CaMKII_minus_thr286
type: KineticLaw

449142
units: 443196
value: 1.5E-17
type: LocalParameter

448172
stoichiometry: 1.0
species: 419286
type: SpeciesReference

421706
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

447473
stoichiometry: 1.0
species: 418606
type: SpeciesReference

444358
stoichiometry: 1.0
species: 419106
type: SpeciesReference

444962
stoichiometry: 1.0
species: 420046
type: SpeciesReference

449951
local parameters: 449451
local parameters: 449450
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

444396
stoichiometry: 1.0
species: 419166
type: SpeciesReference

447436
stoichiometry: 1.0
species: 418586
type: SpeciesReference

449095
units: 443196
value: 1.995E-17
type: LocalParameter

446371
stoichiometry: 1.0
species: 421246
type: SpeciesReference

453363
stoichiometry: 1.0
species: 421966
type: SpeciesReference

445781
stoichiometry: 1.0
species: 420886
type: SpeciesReference

449587
units: 443196
value: 1.2E-15
type: LocalParameter

422406
kinetic law: 443474
product: 443462
reactant: 443449
fast: false
reversible: true
type: Reaction

449806
local parameters: 449443
notes: k3*PKA_minus_active_slash_phosph_minus_PDE_slash_phosph_minus_PDE_cplx
type: KineticLaw

449054
units: 443196
value: 1.5E-16
type: LocalParameter

420846
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.001
initial amount: NaN
in compartment: 418386
type: Species

423925
kinetic law: 446973
product: 446961
reactant: 446949
fast: false
reversible: true
type: Reaction

448907
stoichiometry: 1.0
species: 419726
type: SpeciesReference

449350
units: 443196
value: 0.0
type: LocalParameter

422405
kinetic law: 443437
product: 443425
reactant: 443413
reactant: 443401
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

449588
units: 443196
value: 3.0E-16
type: LocalParameter

451066
stoichiometry: 1.0
species: 420346
type: SpeciesReference

420806
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

450412
local parameters: 449465
notes: k3*CaMKII_slash_tot_CaM_CaMKII_slash_CaM_act_286_slash_CaM_act_286_cplx
type: KineticLaw

443474
local parameters: 449042
local parameters: 449039
notes: kf*PKC_slash_PKC_minus_Ca-kb*PKC_slash_PKC_minus_Ca_minus_memb_star_
type: KineticLaw

449055
units: 443280
value: 1.799955E-18
type: LocalParameter

452472
stoichiometry: 1.0
species: 419346
type: SpeciesReference

452146
stoichiometry: 1.0
species: 421566
type: SpeciesReference

449094
units: 443196
value: 1.5E-15
type: LocalParameter

420886
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

445997
stoichiometry: 1.0
species: 421046
type: SpeciesReference

449351
units: 443196
value: 1.5E-18
type: LocalParameter

452677
stoichiometry: 1.0
species: 421786
type: SpeciesReference

423505
kinetic law: 446057
product: 446045
reactant: 446033
reactant: 446021
fast: false
reversible: true
type: Reaction

447157
stoichiometry: 1.0
species: 418666
type: SpeciesReference

421626
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

420246
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.1
initial amount: NaN
in compartment: 418386
type: Species

446925
stoichiometry: 1.0
species: 422265
type: SpeciesReference

449251
units: 443232
value: 5.399946E-15
type: LocalParameter

449290
units: 443280
value: 2.7E-14
type: LocalParameter

445238
stoichiometry: 1.0
species: 420266
type: SpeciesReference

452931
local parameters: 449569
local parameters: 449566
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

418766
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

421026
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

424365
kinetic law: 448064
product: 448052
product: 448040
reactant: 448028
fast: false
reversible: false
type: Reaction

421066
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

453424
local parameters: 449587
local parameters: 449584
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

418726
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

421566
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

449250
units: 443280
value: 0.0
type: LocalParameter

449291
units: 443196
value: 9.0E-14
type: LocalParameter

421666
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.08
initial amount: NaN
in compartment: 418386
type: Species

445817
local parameters: 449250
local parameters: 449247
notes: kf*PP1_slash_PP1_minus_I1-kb*PP1_minus_active*PP1_slash_I1
type: KineticLaw

449469
units: 443280
value: 2.142855E-17
type: LocalParameter

421886
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

447798
local parameters: 449385
local parameters: 449384
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

449047
units: 443280
value: 9.000045E-19
type: LocalParameter

423005
kinetic law: 444926
product: 444914
reactant: 444902
fast: false
reversible: true
type: Reaction

422226
constant: true
boundary condition: true
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

445925
stoichiometry: 1.0
species: 420966
type: SpeciesReference

422566
kinetic law: 443922
product: 443910
reactant: 443898
reactant: 443886
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

418646
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

447714
stoichiometry: 1.0
species: 418906
type: SpeciesReference

449999
local parameters: 449452
notes: k3*EGFR_slash_L_dot_EGFR_slash_phosph_PLC_g_slash_phosph_PLC_g_cplx
type: KineticLaw

419026
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

449468
units: 443196
value: 9.0E-15
type: LocalParameter

445178
local parameters: 449194
local parameters: 449191
notes: kf*Sos_slash_Sos_star_-kb*Sos_slash_Sos
type: KineticLaw

446551
stoichiometry: 1.0
species: 421326
type: SpeciesReference

452907
stoichiometry: 1.0
species: 422325
type: SpeciesReference

446973
local parameters: 449354
local parameters: 449351
notes: kf*PKM_slash_PKM_synthesis-kb*PKM_slash_PKM_activator
type: KineticLaw

449046
units: 443196
value: 1.5E-16
type: LocalParameter

449195
units: 443280
value: 3.75003E-17
type: LocalParameter

451114
stoichiometry: 1.0
species: 422305
type: SpeciesReference

418606
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.4
initial amount: NaN
in compartment: 418386
type: Species

452219
stoichiometry: 1.0
species: 421286
type: SpeciesReference

422565
kinetic law: 443874
product: 443862
reactant: 443850
fast: false
reversible: true
type: Reaction

452810
stoichiometry: 1.0
species: 422325
type: SpeciesReference

449135
units: 443280
value: 9.000045E-16
type: LocalParameter

451917
local parameters: 449529
local parameters: 449526
notes: kcat*AC_slash_AC2_star__minus_Gs*AC_slash_ATP/(Km+AC_slash_ATP)
type: KineticLaw

420206
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

449467
units: 443196
value: 3.6E-14
type: LocalParameter

447255
stoichiometry: 1.0
species: 418706
type: SpeciesReference

449242
units: 443196
value: 0.0
type: LocalParameter

452786
local parameters: 449561
notes: k3*PKC_minus_active_slash_PKC_minus_act_minus_raf_slash_PKC_minus_act_minus_raf_cplx
type: KineticLaw

451881
stoichiometry: 1.0
species: 422205
type: SpeciesReference

449198
units: 443196
value: 2.52E-17
type: LocalParameter

449138
units: 443196
value: 1.5E-15
type: LocalParameter

451474
local parameters: 449504
notes: k3*PP2A_slash_PP2A_minus_dephosph_minus_I1_slash_PP2A_minus_dephosph_minus_I1_cplx
type: KineticLaw

448340
stoichiometry: 1.0
species: 419446
type: SpeciesReference

452001
stoichiometry: 1.0
species: 421466
type: SpeciesReference

449360
units: 443280
value: 4.140045E-15
type: LocalParameter

451150
stoichiometry: 1.0
species: 420786
type: SpeciesReference

449466
units: 443280
value: 2.571345E-16
type: LocalParameter

444526
stoichiometry: 1.0
species: 419166
type: SpeciesReference

450738
stoichiometry: 1.0
species: 420586
type: SpeciesReference

425785
kinetic law: 451917
modifier: 451905
product: 451893
reactant: 451881
fast: false
reversible: false
type: Reaction

449243
units: 443280
value: 7.499655E-13
type: LocalParameter

420106
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.5
initial amount: NaN
in compartment: 418386
type: Species

445275
local parameters: 449202
local parameters: 449199
notes: kf*PLC_g_slash_PLC_g*Ca-kb*PLC_g_slash_Ca_dot_PLC_g
type: KineticLaw

450230
stoichiometry: 1.0
species: 420426
type: SpeciesReference

452701
stoichiometry: 1.0
species: 419246
type: SpeciesReference

443256
exponent: -2.0
scale: -6
multipler: 1.0
kind: MOLE
type: SBMLUnit

424505
kinetic law: 448400
product: 448388
reactant: 448376
reactant: 448364
notes: See parent PPhosphatase2A for parms
fast: false
reversible: true
type: Reaction

421926
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

447980
stoichiometry: 1.0
species: 419306
type: SpeciesReference

452400
local parameters: 449546
notes: k3*MKP3_slash_nuc_MAPK_star__slash_act_transcription_slash_act_transcription_cplx
type: KineticLaw

422765
kinetic law: 444370
product: 444358
reactant: 444346
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

418586
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

451700
stoichiometry: 1.0
species: 421286
type: SpeciesReference

449199
units: 443280
value: 2.7E-13
type: LocalParameter

446709
local parameters: 449326
local parameters: 449323
notes: kf*AC_slash_PDE1*CaM_minus_Ca4-kb*AC_slash_CaM_dot_PDE1
type: KineticLaw

446407
stoichiometry: 1.0
species: 419966
type: SpeciesReference

424685
kinetic law: 448835
product: 448823
product: 448810
reactant: 448798
fast: false
reversible: false
type: Reaction

449131
units: 443196
value: 1.5E-17
type: LocalParameter

447641
stoichiometry: 1.0
species: 418846
type: SpeciesReference

451663
stoichiometry: 1.0
species: 420966
type: SpeciesReference

451736
stoichiometry: 1.0
species: 422205
type: SpeciesReference

449770
stoichiometry: 1.0
species: 419946
type: SpeciesReference

449246
units: 443196
value: 1.5E-16
type: LocalParameter

422265
constant: true
boundary condition: true
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

447084
stoichiometry: 1.0
species: 422066
type: SpeciesReference

450059
stoichiometry: 1.0
species: 420086
type: SpeciesReference

449134
units: 443232
value: 0.0
type: LocalParameter

426205
kinetic law: 452931
product: 452919
reactant: 452907
reactant: 452895
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

419846
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

424265
kinetic law: 447798
product: 447786
reactant: 447774
reactant: 447762
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

450120
stoichiometry: 1.0
species: 418566
type: SpeciesReference

445383
stoichiometry: 1.0
species: 420346
type: SpeciesReference

423645
kinetic law: 446395
product: 446383
reactant: 446371
reactant: 446359
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

449247
units: 443196
value: 1.5E-15
type: LocalParameter

426245
kinetic law: 453027
product: 453015
reactant: 453003
reactant: 452991
notes: Rates from Huang et al ABB 305:2 570-580 1993
fast: false
reversible: true
type: Reaction

444674
stoichiometry: 1.0
species: 419446
type: SpeciesReference

448052
stoichiometry: 1.0
species: 419366
type: SpeciesReference

452895
stoichiometry: 1.0
species: 419666
type: SpeciesReference

446166
stoichiometry: 1.0
species: 421146
type: SpeciesReference

451772
local parameters: 449517
local parameters: 449516
notes: kcat*AC_slash_AC2_star_*AC_slash_ATP/(Km+AC_slash_ATP)
type: KineticLaw

450556
local parameters: 449470
local parameters: 449469
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

453039
stoichiometry: 1.0
species: 421886
type: SpeciesReference

425905
kinetic law: 452207
product: 452195
product: 452183
reactant: 452170
fast: false
reversible: false
type: Reaction

450897
local parameters: 449483
notes: k3*PP1_minus_active_slash_Deph_minus_thr306_slash_Deph_minus_thr306_cplx
type: KineticLaw

452195
stoichiometry: 1.0
species: 421546
type: SpeciesReference

445022
stoichiometry: 1.0
species: 420046
type: SpeciesReference

447871
stoichiometry: 1.0
species: 422166
type: SpeciesReference

450666
stoichiometry: 1.0
species: 420566
type: SpeciesReference

444782
stoichiometry: 1.0
species: 419726
type: SpeciesReference

449420
units: 443280
value: 2.97E-16
type: LocalParameter

421306
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

449248
stoichiometry: 1.0
species: 419846
type: SpeciesReference

449461
units: 443196
value: 3.6E-14
type: LocalParameter

425125
kinetic law: 450315
product: 450303
product: 450291
reactant: 450279
fast: false
reversible: false
type: Reaction

452858
stoichiometry: 1.0
species: 419766
type: SpeciesReference

443365
stoichiometry: 1.0
species: 421646
type: SpeciesReference

447750
local parameters: 449383
notes: k3*MAPK_star__slash_phosph_Sos_slash_phosph_Sos_cplx
type: KineticLaw

444103
stoichiometry: 1.0
species: 418946
type: SpeciesReference

424865
kinetic law: 449659
product: 449647
reactant: 449635
reactant: 449623
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

446793
stoichiometry: 1.0
species: 422206
type: SpeciesReference

422985
kinetic law: 444890
product: 444878
reactant: 444866
reactant: 444854
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 2 Aug 2004 Raised Kf from 60 to 200 to achieve higher MAPK activation following Ca stimulus for PKM models. 3 Aug 2004. Lowered Kf to 100.
fast: false
reversible: true
type: Reaction

449421
units: 443196
value: 1.2E-16
type: LocalParameter

418426
constant: false
boundary condition: false
has only substance units: false
initial concentration: 3.72077777777778E-17
initial amount: NaN
in compartment: 418386
type: Species

448004
stoichiometry: 1.0
species: 419386
type: SpeciesReference

449315
units: 443280
value: 1.2499245E-12
type: LocalParameter

418986
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

449460
units: 443280
value: 3.961305E-16
type: LocalParameter

450279
stoichiometry: 1.0
species: 420466
type: SpeciesReference

449190
units: 443196
value: 2.52E-17
type: LocalParameter

448702
stoichiometry: 1.0
species: 419586
type: SpeciesReference

449314
units: 443196
value: 1.5E-15
type: LocalParameter

419666
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.1
initial amount: NaN
in compartment: 418386
type: Species

445624
stoichiometry: 1.0
species: 419966
type: SpeciesReference

424545
kinetic law: 448496
product: 448484
reactant: 448472
reactant: 448460
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

419346
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

443994
local parameters: 449090
local parameters: 449087
notes: kf*DAG-kb*PLCbeta_slash_PC
type: KineticLaw

443619
stoichiometry: 1.0
species: 422086
type: SpeciesReference

446757
stoichiometry: 2.0
species: 418846
type: SpeciesReference

446057
local parameters: 449270
local parameters: 449267
notes: kf*CaM_minus_Ca4*CaNAB_minus_Ca4-kb*PP2B_slash_CaMCa4_minus_CaNAB
type: KineticLaw

449529
units: 443160
value: 60.0
type: LocalParameter

448388
stoichiometry: 1.0
species: 419526
type: SpeciesReference

448424
stoichiometry: 1.0
species: 419246
type: SpeciesReference

445672
stoichiometry: 1.0
species: 420686
type: SpeciesReference

443802
stoichiometry: 1.0
species: 418826
type: SpeciesReference

453147
stoichiometry: 1.0
species: 420666
type: SpeciesReference

447605
local parameters: 449379
local parameters: 449378
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

425045
kinetic law: 450095
product: 450083
product: 450071
reactant: 450059
fast: false
reversible: false
type: Reaction

423305
kinetic law: 445588
product: 445576
reactant: 445564
reactant: 445552
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

424825
kinetic law: 449393
product: 449357
reactant: 449345
reactant: 449333
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

449842
stoichiometry: 1.0
species: 420006
type: SpeciesReference

449424
units: 443196
value: 1.2E-16
type: LocalParameter

443886
stoichiometry: 1.0
species: 421646
type: SpeciesReference

449465
units: 443196
value: 7.5E-16
type: LocalParameter

423405
kinetic law: 445817
product: 445805
product: 445793
reactant: 445781
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

423385
kinetic law: 445769
product: 445757
reactant: 445744
reactant: 445732
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

447689
stoichiometry: 1.0
species: 418906
type: SpeciesReference

449525
units: 443160
value: 20.0
type: LocalParameter

446443
local parameters: 449302
local parameters: 449299
notes: kf*CaM_minus_Ca4*AC_slash_AC1-kb*AC_slash_AC1_minus_CaM
type: KineticLaw

444461
stoichiometry: 1.0
species: 419206
type: SpeciesReference

426045
kinetic law: 452545
product: 452533
reactant: 452521
reactant: 452509
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 Km for MKP3 is set to 267 nM, twice as high as MKP1 version, to lessen substrate saturation.
fast: false
reversible: true
type: Reaction

448532
stoichiometry: 1.0
species: 419506
type: SpeciesReference

449425
units: 443196
value: 3.0E-17
type: LocalParameter

444746
stoichiometry: 1.0
species: 419686
type: SpeciesReference

449191
units: 443196
value: 1.5E-18
type: LocalParameter

449139
units: 443280
value: 9.000045E-14
type: LocalParameter

421466
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.45
initial amount: NaN
in compartment: 418386
type: Species

449464
units: 443196
value: 3.0E-15
type: LocalParameter

448280
stoichiometry: 1.0
species: 419446
type: SpeciesReference

449548
units: 443280
value: 2.99997E-15
type: LocalParameter

449311
units: 443280
value: 1.89E-13
type: LocalParameter

421526
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

449526
units: 443196
value: 8.1E-14
type: LocalParameter

425005
kinetic law: 449999
product: 449987
product: 449975
reactant: 449963
fast: false
reversible: false
type: Reaction

450181
stoichiometry: 1.0
species: 418566
type: SpeciesReference

423345
kinetic law: 445684
product: 445672
reactant: 445660
reactant: 445648
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

449422
units: 443196
value: 3.0E-17
type: LocalParameter

444854
stoichiometry: 1.0
species: 419666
type: SpeciesReference

449194
units: 443196
value: 0.0
type: LocalParameter

444296
stoichiometry: 1.0
species: 419106
type: SpeciesReference

449463
units: 443280
value: 3.30102E-17
type: LocalParameter

449310
units: 443196
value: 1.5E-15
type: LocalParameter

446648
stoichiometry: 1.0
species: 421466
type: SpeciesReference

447364
local parameters: 449368
notes: k3*PLA2_slash_DAG_minus_Ca_minus_PLA2_star__slash_kenz_slash_kenz_cplx
type: KineticLaw

423965
kinetic law: 447072
product: 447060
product: 447048
reactant: 447036
fast: false
reversible: false
type: Reaction

425965
kinetic law: 452352
product: 452340
reactant: 452328
reactant: 452316
fast: false
reversible: true
type: Reaction

422945
kinetic law: 444806
product: 444794
reactant: 444782
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

449423
units: 443280
value: 2.97E-16
type: LocalParameter

445335
stoichiometry: 1.0
species: 420326
type: SpeciesReference

445732
stoichiometry: 1.0
species: 420846
type: SpeciesReference

443778
stoichiometry: 1.0
species: 422066
type: SpeciesReference

449462
units: 443196
value: 9.0E-15
type: LocalParameter

424325
kinetic law: 447968
product: 447956
product: 447944
product: 447932
reactant: 447920
fast: false
reversible: false
type: Reaction

419786
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.01
initial amount: NaN
in compartment: 418386
type: Species

419986
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

422525
kinetic law: 443790
product: 443778
reactant: 443766
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

443922
local parameters: 449082
local parameters: 449079
notes: kf*Ca*PLCbeta_slash_PLC-kb*PLCbeta_slash_PLC_minus_Ca
type: KineticLaw

449286
units: 443196
value: 4.875E-14
type: LocalParameter

448304
local parameters: 449403
local parameters: 449402
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

452352
local parameters: 449545
local parameters: 449544
notes: k1*MKP3_slash_nucleotides*MKP3_slash_nuc_MAPK_star_-k2*MKP3_slash_nuc_MAPK_star__slash_act_transcription_slash_act_transcription_cplx
type: KineticLaw

422006
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

448292
stoichiometry: 1.0
species: 419486
type: SpeciesReference

424745
kinetic law: 448982
product: 448969
reactant: 448957
reactant: 448944
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

420606
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

447593
stoichiometry: 1.0
species: 418886
type: SpeciesReference

446214
stoichiometry: 1.0
species: 421286
type: SpeciesReference

449554
units: 443196
value: 2.4E-14
type: LocalParameter

448823
stoichiometry: 1.0
species: 419626
type: SpeciesReference

424785
kinetic law: 449272
product: 449260
reactant: 449248
reactant: 449236
notes: Kinetics same as GEF-bg_act-ras
fast: false
reversible: true
type: Reaction

449418
units: 443196
value: 3.6E-14
type: LocalParameter

449287
units: 443196
value: 9.0E-14
type: LocalParameter

453255
stoichiometry: 1.0
species: 421346
type: SpeciesReference

451426
local parameters: 449503
local parameters: 449502
notes: k1*PP1_slash_I1_star_*PP2A-k2*PP2A_slash_PP2A_minus_dephosph_minus_I1_slash_PP2A_minus_dephosph_minus_I1_cplx
type: KineticLaw

420706
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

449553
units: 443280
value: 2.99997E-15
type: LocalParameter

449720
stoichiometry: 1.0
species: 421466
type: SpeciesReference

452062
local parameters: 449536
local parameters: 449535
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

449419
units: 443196
value: 9.0E-15
type: LocalParameter

423805
kinetic law: 446745
product: 446733
reactant: 446721
fast: false
reversible: true
type: Reaction

449830
stoichiometry: 1.0
species: 419986
type: SpeciesReference

446539
stoichiometry: 1.0
species: 421626
type: SpeciesReference

419946
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

452460
stoichiometry: 1.0
species: 421746
type: SpeciesReference

449082
units: 443196
value: 1.5E-15
type: LocalParameter

448798
stoichiometry: 1.0
species: 419646
type: SpeciesReference

449284
stoichiometry: 1.0
species: 419866
type: SpeciesReference

449498
units: 443196
value: 5.1E-16
type: LocalParameter

443486
stoichiometry: 1.0
species: 418486
type: SpeciesReference

450448
stoichiometry: 1.0
species: 420506
type: SpeciesReference

449552
units: 443196
value: 6.0E-15
type: LocalParameter

450787
stoichiometry: 1.0
species: 420546
type: SpeciesReference

444914
stoichiometry: 1.0
species: 419666
type: SpeciesReference

421106
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.5
initial amount: NaN
in compartment: 418386
type: Species

452316
stoichiometry: 1.0
species: 422206
type: SpeciesReference

420786
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

444890
local parameters: 449166
local parameters: 449163
notes: kf*Ras_slash_inact_minus_GEF*CaM_minus_Ca4-kb*Ras_slash_CaM_minus_GEF
type: KineticLaw

445540
local parameters: 449226
local parameters: 449223
notes: kf*CaM_slash_CaM*Ca^2-kb*CaM_minus_TR2_minus_Ca2
type: KineticLaw

449083
units: 443196
value: 3.75E-15
type: LocalParameter

453219
stoichiometry: 1.0
species: 421926
type: SpeciesReference

449499
units: 443280
value: 5.13E-16
type: LocalParameter

420746
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

425085
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.
fast: false
product: 450181
reactant: 450169
kinetic law: 450218
product: 450194
type: Reaction
modifier: 450206
reversible: false

448136
stoichiometry: 1.0
species: 418846
type: SpeciesReference

449551
units: 443196
value: 2.4E-14
type: LocalParameter

447895
stoichiometry: 1.0
species: 419026
type: SpeciesReference

419266
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

446733
stoichiometry: 1.0
species: 421646
type: SpeciesReference

451953
stoichiometry: 1.0
species: 421486
type: SpeciesReference

452086
stoichiometry: 1.0
species: 421426
type: SpeciesReference

450775
stoichiometry: 1.0
species: 420426
type: SpeciesReference

450836
stoichiometry: 1.0
species: 420606
type: SpeciesReference

453375
local parameters: 449582
notes: k3*PKM_slash_PKM_synthesis_slash_kenz_slash_kenz_cplx
type: KineticLaw

422086
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: 418386
type: Species

449496
units: 443280
value: 5.13E-16
type: LocalParameter

449659
local parameters: 449439
local parameters: 449438
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

449282
units: 443196
value: 1.65E-13
type: LocalParameter

449415
units: 443196
value: 3.6E-14
type: LocalParameter

447485
stoichiometry: 1.0
species: 418846
type: SpeciesReference

449558
units: 443196
value: 1.5E-17
type: LocalParameter

449130
units: 443196
value: 1.5E-16
type: LocalParameter

445359
local parameters: 449210
local parameters: 449207
notes: kf*PLC_g_slash_Ca_dot_PLC_g_star_-kb*PLC_g_slash_Ca_dot_PLC_g
type: KineticLaw

443790
local parameters: 449070
local parameters: 449067
notes: kf*AA-kb*PLA2_slash_APC
type: KineticLaw

445853
stoichiometry: 1.0
species: 420966
type: SpeciesReference

421786
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0014
initial amount: NaN
in compartment: 418386
type: Species

425205
kinetic law: 450508
product: 450496
product: 450484
reactant: 450472
fast: false
reversible: false
type: Reaction

449497
units: 443196
value: 2.04E-15
type: LocalParameter

449283
units: 443280
value: 1.1249955E-13
type: LocalParameter

449414
units: 443280
value: 2.87415E-15
type: LocalParameter

451523
local parameters: 449506
local parameters: 449505
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

421446
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

421746
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

449557
units: 443196
value: 6.0E-17
type: LocalParameter

450484
stoichiometry: 1.0
species: 420406
type: SpeciesReference

447048
stoichiometry: 1.0
species: 418586
type: SpeciesReference

449170
units: 443196
value: 0.0
type: LocalParameter

444998
stoichiometry: 1.0
species: 420106
type: SpeciesReference

445058
stoichiometry: 1.0
species: 420206
type: SpeciesReference

421346
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

447557
local parameters: 449377
notes: k3*MAPK_star__slash_MAPK_star__slash_MAPK_star__cplx
type: KineticLaw

446250
local parameters: 449286
local parameters: 449283
notes: kf*cAMP*PKA_slash_R2C2_minus_cAMP3-kb*PKA_slash_R2C2_minus_cAMP4
type: KineticLaw

451639
stoichiometry: 1.0
species: 420986
type: SpeciesReference

424445
kinetic law: 448256
product: 448244
product: 448232
reactant: 448220
fast: false
reversible: false
type: Reaction

449494
units: 443196
value: 4.005E-15
type: LocalParameter

418966
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

449417
units: 443280
value: 2.87415E-15
type: LocalParameter

418846
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

423425
kinetic law: 445865
product: 445853
reactant: 445841
reactant: 445829
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

425285
kinetic law: 450702
product: 450690
product: 450678
reactant: 450666
fast: false
reversible: false
type: Reaction

446322
stoichiometry: 1.0
species: 419886
type: SpeciesReference

444564
stoichiometry: 1.0
species: 419146
type: SpeciesReference

449556
units: 443280
value: 3.75003E-16
type: LocalParameter

418566
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

443607
local parameters: 449054
local parameters: 449051
notes: kf*PLA2_slash_PLA2_minus_cytosolic*Ca-kb*PLA2_slash_PLA2_minus_Ca_star_
type: KineticLaw

424105
kinetic law: 447412
product: 447400
reactant: 447388
reactant: 447376
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

449495
units: 443196
value: 1.005E-15
type: LocalParameter

452557
stoichiometry: 1.0
species: 421766
type: SpeciesReference

451562
stoichiometry: 1.0
species: 420906
type: SpeciesReference

444163
stoichiometry: 1.0
species: 419046
type: SpeciesReference

449416
units: 443196
value: 9.0E-15
type: LocalParameter

443595
stoichiometry: 1.0
species: 418626
type: SpeciesReference

446805
stoichiometry: 1.0
species: 421786
type: SpeciesReference

447629
stoichiometry: 1.0
species: 419326
type: SpeciesReference

444235
local parameters: 449110
local parameters: 449107
notes: kf*Gq_slash_mGluR*Glu-kb*Gq_slash_Rec_minus_Glu
type: KineticLaw

421386
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.015
initial amount: NaN
in compartment: 418386
type: Species

449555
units: 443196
value: 6.0E-15
type: LocalParameter

423465
kinetic law: 445961
product: 445949
reactant: 445937
reactant: 445925
notes: Disabled. See notes for PP2B7.g
fast: false
reversible: true
type: Reaction

444638
local parameters: 449142
local parameters: 449139
notes: kf*Gq_slash_Rec_minus_Gq*Gq_slash_mGluRAntag-kb*Gq_slash_Blocked_minus_rec_minus_Gq
type: KineticLaw

425925
kinetic law: 452255
product: 452243
reactant: 452231
reactant: 452219
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

451282
local parameters: 449498
notes: k3*CaM_po_Ca_pc_n_minus_CaNAB_slash_dephosph_inhib1_slash_dephosph_inhib1_cplx
type: KineticLaw

418886
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

446094
stoichiometry: 1.0
species: 421126
type: SpeciesReference

453183
local parameters: 449576
notes: k3*PKC_minus_active_slash_PKC_minus_phosph_minus_ng_minus_CaM_slash_PKC_minus_phosph_minus_ng_minus_CaM_cplx
type: KineticLaw

419106
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

452943
stoichiometry: 1.0
species: 421866
type: SpeciesReference

446913
stoichiometry: 1.0
species: 418546
type: SpeciesReference

426285
kinetic law: 453123
product: 453111
reactant: 453099
reactant: 453087
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

449306
units: 443196
value: 0.0
type: LocalParameter

423665
kinetic law: 446443
product: 446431
reactant: 446419
reactant: 446407
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

451498
stoichiometry: 1.0
species: 420906
type: SpeciesReference

445961
local parameters: 449262
local parameters: 449259
notes: kf*CaNAB_minus_Ca4*CaM_minus_TR2_minus_Ca2-kb*PP2B_slash_CaMCa2_minus_CANAB
type: KineticLaw

426385
kinetic law: 453375
product: 453363
product: 453351
reactant: 453339
fast: false
reversible: false
type: Reaction

449387
units: 443280
value: 7.199955E-14
type: LocalParameter

447145
stoichiometry: 1.0
species: 418586
type: SpeciesReference

452665
stoichiometry: 1.0
species: 421726
type: SpeciesReference

445805
stoichiometry: 1.0
species: 420826
type: SpeciesReference

418706
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

426345
kinetic law: 453279
product: 453267
product: 453255
reactant: 453243
fast: false
reversible: false
type: Reaction

443643
stoichiometry: 1.0
species: 418666
type: SpeciesReference

453436
stoichiometry: 1.0
species: 422026
type: SpeciesReference

450376
stoichiometry: 1.0
species: 420486
type: SpeciesReference

449388
units: 443196
value: 2.88E-13
type: LocalParameter

449174
units: 443196
value: 3.75E-16
type: LocalParameter

443268
exponent: -1.0
scale: 0
multipler: 1.0
kind: SECOND
type: SBMLUnit

445588
local parameters: 449230
local parameters: 449227
notes: kf*CaM_minus_TR2_minus_Ca2*Ca-kb*CaM_minus_Ca3
type: KineticLaw

449171
units: 443280
value: 6.300045E-15
type: LocalParameter

423245
kinetic law: 445456
product: 445444
reactant: 445432
reactant: 445420
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

425525
kinetic law: 451282
product: 451270
product: 451258
reactant: 451246
fast: false
reversible: false
type: Reaction

425465
kinetic law: 451138
product: 451126
reactant: 451114
reactant: 451102
notes: From Seki et al ABB 316(2):673-679
fast: false
reversible: true
type: Reaction

449308
stoichiometry: 1.0
species: 419846
type: SpeciesReference

447834
stoichiometry: 1.0
species: 418926
type: SpeciesReference

449385
units: 443196
value: 6.0E-14
type: LocalParameter

450291
stoichiometry: 1.0
species: 420406
type: SpeciesReference

447400
stoichiometry: 1.0
species: 418806
type: SpeciesReference

449599
stoichiometry: 1.0
species: 419886
type: SpeciesReference

452134
stoichiometry: 1.0
species: 421546
type: SpeciesReference

421166
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

419186
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

426085
kinetic law: 452641
product: 452629
reactant: 452617
reactant: 452605
fast: false
reversible: true
type: Reaction

447096
stoichiometry: 1.0
species: 418666
type: SpeciesReference

449307
units: 443280
value: 7.499925E-13
type: LocalParameter

444054
stoichiometry: 1.0
species: 419006
type: SpeciesReference

451078
stoichiometry: 1.0
species: 420546
type: SpeciesReference

444383
stoichiometry: 1.0
species: 419126
type: SpeciesReference

426305
kinetic law: 453183
product: 453171
product: 453159
product: 453147
reactant: 453135
fast: false
reversible: false
type: Reaction

450400
stoichiometry: 1.0
species: 422285
type: SpeciesReference

449386
units: 443196
value: 1.5E-14
type: LocalParameter

425565
kinetic law: 451378
product: 451366
product: 451354
reactant: 451342
fast: false
reversible: false
type: Reaction

443535
stoichiometry: 1.0
species: 418566
type: SpeciesReference

449550
stoichiometry: 1.0
species: 419826
type: SpeciesReference

425685
kinetic law: 451676
product: 451663
product: 451651
reactant: 451639
fast: false
reversible: false
type: Reaction

419626
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

451318
stoichiometry: 1.0
species: 419606
type: SpeciesReference

420186
constant: false
boundary condition: false
has only substance units: false
initial concentration: 1.0
initial amount: NaN
in compartment: 418386
type: Species

445432
stoichiometry: 1.0
species: 419966
type: SpeciesReference

445166
stoichiometry: 1.0
species: 420246
type: SpeciesReference

444346
stoichiometry: 1.0
species: 419086
type: SpeciesReference

420146
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

444950
stoichiometry: 1.0
species: 422186
type: SpeciesReference

449611
local parameters: 449437
notes: k3*PKA_minus_active_slash_PKA_minus_phosph_minus_GEF_slash_PKA_minus_phosph_minus_GEF_cplx
type: KineticLaw

448184
stoichiometry: 1.0
species: 419446
type: SpeciesReference

423625
kinetic law: 446347
product: 446335
product: 446322
reactant: 446310
fast: false
reversible: true
type: Reaction

449178
units: 443196
value: 0.0
type: LocalParameter

419766
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

422605
kinetic law: 443994
product: 443982
reactant: 443970
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

449086
units: 443196
value: 0.0
type: LocalParameter

420586
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

419486
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

443850
stoichiometry: 1.0
species: 418826
type: SpeciesReference

425605
kinetic law: 451474
product: 451462
product: 451450
reactant: 451438
fast: false
reversible: false
type: Reaction

447944
stoichiometry: 1.0
species: 418926
type: SpeciesReference

451845
stoichiometry: 1.0
species: 421286
type: SpeciesReference

420546
constant: false
boundary condition: false
has only substance units: false
initial concentration: 1.8
initial amount: NaN
in compartment: 418386
type: Species

449175
units: 443196
value: 2.50005E-18
type: LocalParameter

453075
local parameters: 449573
notes: k3*PKC_minus_active_slash_PKC_minus_phosph_minus_neurogranin_slash_PKC_minus_phosph_minus_neurogranin_cplx
type: KineticLaw

448244
stoichiometry: 1.0
species: 419446
type: SpeciesReference

449389
units: 443196
value: 7.2E-14
type: LocalParameter

449087
units: 443196
value: 2.25E-16
type: LocalParameter

447108
stoichiometry: 1.0
species: 418686
type: SpeciesReference

451784
stoichiometry: 1.0
species: 422205
type: SpeciesReference

449903
local parameters: 449449
notes: k3*Shc_star__dot_Sos_dot_Grb2_slash_Sos_dot_Ras_GEF_slash_Sos_dot_Ras_GEF_cplx
type: KineticLaw

418466
constant: false
boundary condition: false
has only substance units: false
initial concentration: 9.43511111111111E-21
initial amount: NaN
in compartment: 418386
type: Species

446624
local parameters: 449318
local parameters: 449315
notes: kf*Gs_minus_alpha*AC_slash_AC2_star_-kb*AC_slash_AC2_star__minus_Gs
type: KineticLaw

446298
local parameters: 449290
local parameters: 449287
notes: kf*PKA_slash_R2C2_minus_cAMP4-kb*PKA_minus_active*PKA_slash_R2C_minus_cAMP4
type: KineticLaw

421806
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

424045
kinetic law: 447267
product: 447255
product: 447242
reactant: 447230
fast: false
reversible: false
type: Reaction

450095
local parameters: 449455
notes: k3*EGFR_slash_L_dot_EGFR_slash_phosph_Shc_slash_phosph_Shc_cplx
type: KineticLaw

419446
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

419226
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

443437
local parameters: 449038
local parameters: 449035
notes: kf*DAG*PKC_slash_PKC_minus_Ca-kb*PKC_slash_PKC_minus_Ca_minus_DAG
type: KineticLaw

420646
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

445744
stoichiometry: 1.0
species: 420546
type: SpeciesReference

450047
local parameters: 449454
local parameters: 449453
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

443184
exponent: 1.0
scale: -6
multipler: 1.0
kind: MOLE
type: SBMLUnit

449459
units: 443160
value: 19.7916666666667
type: LocalParameter

451030
stoichiometry: 1.0
species: 420646
type: SpeciesReference

424905
kinetic law: 449757
product: 449745
reactant: 449733
reactant: 449720
notes: Same rates as PKA-phosph-I1
fast: false
reversible: true
type: Reaction

447449
stoichiometry: 1.0
species: 418786
type: SpeciesReference

449234
units: 443196
value: 1.5E-14
type: LocalParameter

450157
local parameters: 449457
local parameters: 449456
notes: kcat*PLC_g_slash_Ca_dot_PLC_g*PIP2/(Km+PIP2)
type: KineticLaw

450909
stoichiometry: 1.0
species: 420406
type: SpeciesReference

453027
local parameters: 449572
local parameters: 449571
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

450520
stoichiometry: 1.0
species: 420366
type: SpeciesReference

443425
stoichiometry: 1.0
species: 418486
type: SpeciesReference

446636
stoichiometry: 1.0
species: 421506
type: SpeciesReference

448944
stoichiometry: 1.0
species: 419726
type: SpeciesReference

448040
stoichiometry: 1.0
species: 419346
type: SpeciesReference

424945
kinetic law: 449854
product: 449842
reactant: 449830
reactant: 449818
fast: false
reversible: true
type: Reaction

446178
stoichiometry: 1.0
species: 421286
type: SpeciesReference

449391
units: 443280
value: 4.86E-14
type: LocalParameter

449235
units: 443280
value: 4.499955E-16
type: LocalParameter

422905
kinetic law: 444734
product: 444722
reactant: 444710
reactant: 444698
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

449458
units: 443196
value: 8.55E-14
type: LocalParameter

445793
stoichiometry: 1.0
species: 420546
type: SpeciesReference

422825
product: 444500
reactant: 444487
product: 444513
fast: false
kinetic law: 444539
product: 444526
reversible: true
type: Reaction
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.

446673
stoichiometry: 1.0
species: 421546
type: SpeciesReference

447992
stoichiometry: 1.0
species: 419366
type: SpeciesReference

452412
stoichiometry: 1.0
species: 418846
type: SpeciesReference

423845
kinetic law: 446817
product: 446805
reactant: 446793
notes: Reverse reaction is for turning off the synthesis.
fast: false
reversible: true
type: Reaction

426125
kinetic law: 452737
product: 452725
reactant: 452713
reactant: 452701
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 3 Aug 2004. Lowered Km from 66.66 to 3.33, to match that of PKC-inact-GAP
fast: false
reversible: true
type: Reaction

449127
units: 443280
value: 2.520045E-14
type: LocalParameter

452883
local parameters: 449564
notes: k3*PKC_minus_active_slash_PKC_minus_inact_minus_GAP_slash_PKC_minus_inact_minus_GAP_cplx
type: KineticLaw

443220
exponent: -1.0
scale: 0
multipler: 1.0
kind: SECOND
type: SBMLUnit

448568
stoichiometry: 1.0
species: 419506
type: SpeciesReference

452737
local parameters: 449560
local parameters: 449559
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

446479
local parameters: 449306
local parameters: 449303
notes: kf*AC_slash_AC2_star_-kb*AC_slash_AC2
type: KineticLaw

422046
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0944444444444444
initial amount: NaN
in compartment: 418386
type: Species

449167
units: 443196
value: 1.5E-15
type: LocalParameter

451748
stoichiometry: 1.0
species: 421286
type: SpeciesReference

422865
kinetic law: 444638
product: 444626
reactant: 444614
reactant: 444601
notes: The rate consts give a total binding affinity of only
fast: false
reversible: true
type: Reaction

451390
stoichiometry: 1.0
species: 420846
type: SpeciesReference

449396
units: 443280
value: 4.86E-14
type: LocalParameter

450945
local parameters: 449485
local parameters: 449484
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

452013
local parameters: 449534
notes: k3*AC_slash_cAMP_minus_PDE_slash_PDE_slash_PDE_cplx
type: KineticLaw

448412
stoichiometry: 1.0
species: 419526
type: SpeciesReference

445708
stoichiometry: 1.0
species: 420726
type: SpeciesReference

451462
stoichiometry: 1.0
species: 420906
type: SpeciesReference

424405
kinetic law: 448160
product: 448148
product: 448136
reactant: 448124
fast: false
reversible: false
type: Reaction

448352
local parameters: 449404
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

449342
units: 443196
value: 0.0
type: LocalParameter

447846
stoichiometry: 1.0
species: 418966
type: SpeciesReference

449230
units: 443196
value: 1.5E-14
type: LocalParameter

418686
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

447193
stoichiometry: 1.0
species: 418706
type: SpeciesReference

452629
stoichiometry: 1.0
species: 421806
type: SpeciesReference

449455
units: 443196
value: 3.0E-16
type: LocalParameter

449395
units: 443196
value: 4.5E-16
type: LocalParameter

418526
constant: false
boundary condition: false
has only substance units: false
initial concentration: 1.0
initial amount: NaN
in compartment: 418386
type: Species

453291
stoichiometry: 1.0
species: 422246
type: SpeciesReference

445287
stoichiometry: 1.0
species: 421646
type: SpeciesReference

449302
units: 443196
value: 1.5E-15
type: LocalParameter

445214
stoichiometry: 1.0
species: 420206
type: SpeciesReference

425245
kinetic law: 450606
product: 450593
product: 450580
reactant: 450568
fast: false
reversible: false
type: Reaction

449454
units: 443196
value: 1.2E-15
type: LocalParameter

420266
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.82
initial amount: NaN
in compartment: 418386
type: Species

449231
units: 443280
value: 6.975045E-16
type: LocalParameter

444409
stoichiometry: 1.0
species: 419206
type: SpeciesReference

451162
stoichiometry: 1.0
species: 420726
type: SpeciesReference

447726
stoichiometry: 1.0
species: 420226
type: SpeciesReference

449987
stoichiometry: 1.0
species: 420046
type: SpeciesReference

449394
units: 443196
value: 1.8E-15
type: LocalParameter

449031
units: 443280
value: 9.000045E-16
type: LocalParameter

449303
units: 443196
value: 1.5E-16
type: LocalParameter

424485
kinetic law: 448352
product: 448340
product: 448328
reactant: 448316
fast: false
reversible: false
type: Reaction

423526
kinetic law: 446106
product: 446094
reactant: 446081
reactant: 446069
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

446588
stoichiometry: 1.0
species: 421626
type: SpeciesReference

449457
units: 443160
value: 97.2222222222222
type: LocalParameter

444115
stoichiometry: 1.0
species: 419086
type: SpeciesReference

451676
local parameters: 449513
notes: k3*CaNAB_minus_Ca4_slash_dephosph_inhib1_noCaM_slash_dephosph_inhib1_noCaM_cplx
type: KineticLaw

421406
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

444513
stoichiometry: 1.0
species: 419066
type: SpeciesReference

418926
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.73
initial amount: NaN
in compartment: 418386
type: Species

420926
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

420966
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

419406
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

449393
local parameters: 449436
local parameters: 449435
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

449030
local parameters: 449431
notes: k3*Ras_slash_GAP_slash_GAP_minus_inact_minus_ras_slash_GAP_minus_inact_minus_ras_cplx
type: KineticLaw

444448
stoichiometry: 1.0
species: 419186
type: SpeciesReference

452581
stoichiometry: 1.0
species: 421726
type: SpeciesReference

449343
units: 443232
value: 1.500039E-16
type: LocalParameter

451126
stoichiometry: 1.0
species: 420786
type: SpeciesReference

444090
local parameters: 449098
local parameters: 449095
notes: kf*PLCbeta_slash_PLC_minus_Ca_minus_Gq-kb*G_star_GDP*PLCbeta_slash_PLC_minus_Ca
type: KineticLaw

449456
units: 443196
value: 2.1E-14
type: LocalParameter

446961
stoichiometry: 1.0
species: 422046
type: SpeciesReference

423785
kinetic law: 446709
product: 446697
reactant: 446685
reactant: 446673
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

450568
stoichiometry: 1.0
species: 420526
type: SpeciesReference

446130
stoichiometry: 1.0
species: 421286
type: SpeciesReference

449346
units: 443196
value: 6.0E-16
type: LocalParameter

449451
units: 443196
value: 1.2E-15
type: LocalParameter

444686
local parameters: 449146
local parameters: 449143
notes: kf*MAPK_slash_craf_minus_1_star_*Ras_slash_GTP_minus_Ras-kb*MAPK_slash_Raf_star__minus_GTP_minus_Ras
type: KineticLaw

448088
stoichiometry: 1.0
species: 419366
type: SpeciesReference

447376
stoichiometry: 1.0
species: 422066
type: SpeciesReference

448605
stoichiometry: 1.0
species: 419566
type: SpeciesReference

443742
stoichiometry: 1.0
species: 418746
type: SpeciesReference

445395
stoichiometry: 1.0
species: 420366
type: SpeciesReference

420326
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

449345
stoichiometry: 1.0
species: 419886
type: SpeciesReference

448750
stoichiometry: 1.0
species: 419746
type: SpeciesReference

449450
units: 443280
value: 4.499955E-15
type: LocalParameter

449122
units: 443196
value: 0.0
type: LocalParameter

425865
kinetic law: 452110
product: 452098
product: 452086
reactant: 452074
fast: false
reversible: false
type: Reaction

423205
kinetic law: 445359
product: 445347
reactant: 445335
fast: false
reversible: true
type: Reaction

448460
stoichiometry: 1.0
species: 419366
type: SpeciesReference

447509
local parameters: 449376
local parameters: 449373
notes: k1*PLA2_slash_PLA2_minus_cytosolic*MAPK_star_-k2*MAPK_star__slash_MAPK_star__slash_MAPK_star__cplx
type: KineticLaw

445323
local parameters: 449206
local parameters: 449203
notes: kf*Ca*PLC_g_slash_PLC_G_star_-kb*PLC_g_slash_Ca_dot_PLC_g_star_
type: KineticLaw

424225
kinetic law: 447702
product: 447689
reactant: 447677
reactant: 447665
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

445094
local parameters: 449186
local parameters: 449183
notes: kf*Sos_slash_Sos_dot_Grb2*EGFR_slash_SHC_star_-kb*Shc_star__dot_Sos_dot_Grb2
type: KineticLaw

421266
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

443704
local parameters: 449062
local parameters: 449059
notes: kf*temp_minus_PIP2*PLA2_slash_PLA2_minus_Ca_star_-kb*PLA2_slash_PIP2_minus_Ca_minus_PLA2_star_
type: KineticLaw

444006
stoichiometry: 1.0
species: 419086
type: SpeciesReference

446853
local parameters: 449342
local parameters: 449339
notes: kf*MKP3_slash_MKP_minus_3-kb*MKP3_slash_ubiquitination
type: KineticLaw

447677
stoichiometry: 1.0
species: 418846
type: SpeciesReference

446431
stoichiometry: 1.0
species: 421306
type: SpeciesReference

450993
local parameters: 449486
notes: k3*PP1_minus_active_slash_Deph_minus_thr286c_slash_Deph_minus_thr286c_cplx
type: KineticLaw

450618
stoichiometry: 1.0
species: 420386
type: SpeciesReference

424145
kinetic law: 447509
product: 447497
reactant: 447485
reactant: 447473
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

449559
units: 443280
value: 1.499985E-15
type: LocalParameter

448208
local parameters: 449400
local parameters: 449399
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

451234
local parameters: 449497
local parameters: 449496
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

449453
units: 443280
value: 1.799955E-15
type: LocalParameter

443898
stoichiometry: 1.0
species: 418946
type: SpeciesReference

449412
units: 443196
value: 3.6E-14
type: LocalParameter

423285
kinetic law: 445540
product: 445528
reactant: 445516
reactant: 445504
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

449347
units: 443196
value: 7.5E-19
type: LocalParameter

452292
stoichiometry: 1.0
species: 421586
type: SpeciesReference

449452
units: 443196
value: 3.0E-16
type: LocalParameter

449413
units: 443196
value: 9.0E-15
type: LocalParameter

444734
local parameters: 449150
local parameters: 449147
notes: kf*BetaGamma*Ras_slash_inact_minus_GEF-kb*Ras_slash_GEF_minus_Gprot_minus_bg
type: KineticLaw

444271
stoichiometry: 1.0
species: 419066
type: SpeciesReference

424185
kinetic law: 447605
product: 447593
reactant: 447581
reactant: 447569
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

451354
stoichiometry: 1.0
species: 420886
type: SpeciesReference

449879
stoichiometry: 1.0
species: 419726
type: SpeciesReference

422305
constant: false
boundary condition: true
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

448520
stoichiometry: 1.0
species: 419426
type: SpeciesReference

419146
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.3
initial amount: NaN
in compartment: 418386
type: Species

420486
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

425645
kinetic law: 451576
product: 451562
product: 451549
reactant: 451536
fast: false
reversible: false
type: Reaction

449238
units: 443196
value: 1.5E-15
type: LocalParameter

424085
kinetic law: 447364
product: 447352
product: 447340
reactant: 447328
fast: false
reversible: false
type: Reaction

425705
kinetic law: 451724
modifier: 451712
product: 451700
reactant: 451688
fast: false
reversible: false
type: Reaction

445636
local parameters: 449234
local parameters: 449231
notes: kf*CaM_minus_Ca3*Ca-kb*CaM_minus_Ca4
type: KineticLaw

448714
stoichiometry: 1.0
species: 419266
type: SpeciesReference

450726
stoichiometry: 1.0
species: 420546
type: SpeciesReference

452243
stoichiometry: 1.0
species: 421606
type: SpeciesReference

449279
units: 443280
value: 1.1249955E-13
type: LocalParameter

425305
kinetic law: 450750
product: 450738
reactant: 450726
reactant: 450714
fast: false
reversible: true
type: Reaction

443814
stoichiometry: 1.0
species: 421646
type: SpeciesReference

445684
local parameters: 449238
local parameters: 449235
notes: kf*CaM_slash_neurogranin*CaM_slash_CaM-kb*CaM_slash_neurogranin_minus_CaM
type: KineticLaw

449126
units: 443196
value: 1.5E-19
type: LocalParameter

449239
units: 443196
value: 7.5E-18
type: LocalParameter

443691
stoichiometry: 1.0
species: 418706
type: SpeciesReference

452774
stoichiometry: 1.0
species: 422325
type: SpeciesReference

449278
units: 443196
value: 4.95E-14
type: LocalParameter

451893
stoichiometry: 1.0
species: 421286
type: SpeciesReference

446021
stoichiometry: 1.0
species: 419966
type: SpeciesReference

450266
local parameters: 449461
local parameters: 449460
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

449123
units: 443280
value: 9.000045E-18
type: LocalParameter

419726
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

452846
stoichiometry: 1.0
species: 421846
type: SpeciesReference

420066
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

443377
stoichiometry: 1.0
species: 418426
type: SpeciesReference

422645
kinetic law: 444090
product: 444078
product: 444066
reactant: 444054
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

453327
local parameters: 449581
local parameters: 449580
notes: k1*PKM_slash_AA_pool*PKM_slash_PKM_synthesis-k2*PKM_slash_PKM_synthesis_slash_kenz_slash_kenz_cplx
type: KineticLaw

449236
stoichiometry: 1.0
species: 419746
type: SpeciesReference

444794
stoichiometry: 1.0
species: 419746
type: SpeciesReference

423045
kinetic law: 445010
product: 444998
reactant: 444986
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

445010
local parameters: 449178
local parameters: 449175
notes: kf*EGFR_slash_SHC_star_-kb*EGFR_slash_SHC
type: KineticLaw

444842
local parameters: 449162
local parameters: 449159
notes: kf*Ras_slash_GAP_star_-kb*Ras_slash_GAP
type: KineticLaw

452207
local parameters: 449540
notes: k3*AC_slash_PDE1_slash_PDE1_slash_PDE1_cplx
type: KineticLaw

423105
kinetic law: 445142
product: 445130
reactant: 445118
reactant: 445106
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

452183
stoichiometry: 1.0
species: 421426
type: SpeciesReference

450885
stoichiometry: 1.0
species: 420546
type: SpeciesReference

450678
stoichiometry: 1.0
species: 420366
type: SpeciesReference

423145
kinetic law: 445226
product: 445214
reactant: 445202
reactant: 445190
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

447907
local parameters: 449388
local parameters: 449387
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

424005
kinetic law: 447169
product: 447157
product: 447145
reactant: 447132
fast: false
reversible: false
type: Reaction

421846
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

445913
local parameters: 449258
local parameters: 449255
notes: kf*PP2B_slash_CaNAB*Ca^2-kb*PP2B_slash_CaNAB_minus_Ca2
type: KineticLaw

423085
kinetic law: 445094
product: 445082
reactant: 445070
reactant: 445058
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

419086
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

446781
local parameters: 449334
local parameters: 449331
notes: kf*MAPK_star_^2-kb*MKP3_slash_nuc_MAPK_star_
type: KineticLaw

447786
stoichiometry: 1.0
species: 418986
type: SpeciesReference

444806
local parameters: 449158
local parameters: 449155
notes: kf*Ras_slash_GTP_minus_Ras-kb*Ras_slash_GDP_minus_Ras
type: KineticLaw

449272
local parameters: 449433
local parameters: 449432
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

449486
units: 443196
value: 5.25E-16
type: LocalParameter

443498
stoichiometry: 1.0
species: 418466
type: SpeciesReference

449070
units: 443196
value: 0.0
type: LocalParameter

452304
local parameters: 449543
notes: k3*AC_slash_CaM_dot_PDE1_slash_CaM_dot_PDE1_slash_CaM_dot_PDE1_cplx
type: KineticLaw

448982
local parameters: 449430
local parameters: 449427
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

450436
stoichiometry: 1.0
species: 422286
type: SpeciesReference

449564
units: 443196
value: 6.0E-15
type: LocalParameter

419906
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

444902
stoichiometry: 1.0
species: 419826
type: SpeciesReference

450799
local parameters: 449480
notes: k3*PP1_minus_active_slash_Deph_minus_thr305_slash_Deph_minus_thr305_cplx
type: KineticLaw

449487
units: 443280
value: 5.147955E-16
type: LocalParameter

418806
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

448148
stoichiometry: 1.0
species: 419366
type: SpeciesReference

449071
units: 443280
value: 9.000045E-15
type: LocalParameter

423885
kinetic law: 446901
product: 446889
reactant: 446877
reactant: 446865
fast: false
reversible: true
type: Reaction

421226
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

450824
stoichiometry: 1.0
species: 420546
type: SpeciesReference

453387
stoichiometry: 1.0
species: 422046
type: SpeciesReference

425105
kinetic law: 450266
product: 450254
reactant: 450242
reactant: 450230
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

449409
units: 443280
value: 2.87415E-15
type: LocalParameter

447883
stoichiometry: 1.0
species: 419006
type: SpeciesReference

422465
kinetic law: 443655
product: 443643
reactant: 443631
reactant: 443619
fast: false
reversible: true
type: Reaction

449563
units: 443196
value: 2.4E-14
type: LocalParameter

451941
stoichiometry: 1.0
species: 421466
type: SpeciesReference

450763
stoichiometry: 1.0
species: 420586
type: SpeciesReference

452098
stoichiometry: 1.0
species: 421506
type: SpeciesReference

446721
stoichiometry: 1.0
species: 421666
type: SpeciesReference

449274
units: 443196
value: 4.95E-14
type: LocalParameter

443934
stoichiometry: 1.0
species: 418926
type: SpeciesReference

453279
local parameters: 449579
notes: k3*PKC_minus_active_slash_phosph_minus_AC2_slash_phosph_minus_AC2_cplx
type: KineticLaw

449488
units: 443196
value: 2.1E-15
type: LocalParameter

449407
units: 443196
value: 9.0E-15
type: LocalParameter

449566
units: 443280
value: 9.000045E-15
type: LocalParameter

446889
stoichiometry: 1.0
species: 422006
type: SpeciesReference

448835
local parameters: 449422
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

446202
local parameters: 449282
local parameters: 449279
notes: kf*PKA_slash_R2C2_minus_cAMP2*cAMP-kb*PKA_slash_R2C2_minus_cAMP3
type: KineticLaw

425185
kinetic law: 450460
product: 450448
reactant: 450436
reactant: 450424
notes: See Hanson and Schulman again, for afterburst rates of phosph.
fast: false
reversible: true
type: Reaction

449671
stoichiometry: 1.0
species: 419926
type: SpeciesReference

452340
stoichiometry: 1.0
species: 421706
type: SpeciesReference

453267
stoichiometry: 1.0
species: 422325
type: SpeciesReference

449275
units: 443280
value: 8.1E-14
type: LocalParameter

425145
kinetic law: 450364
product: 450352
reactant: 450340
reactant: 450327
fast: false
reversible: true
type: Reaction

446949
stoichiometry: 1.0
species: 421966
type: SpeciesReference

451414
stoichiometry: 1.0
species: 420926
type: SpeciesReference

449489
units: 443196
value: 5.25E-16
type: LocalParameter

449406
units: 443196
value: 3.6E-14
type: LocalParameter

452074
stoichiometry: 1.0
species: 421526
type: SpeciesReference

425725
kinetic law: 451772
modifier: 451760
product: 451748
reactant: 451736
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

443679
stoichiometry: 1.0
species: 418626
type: SpeciesReference

449405
units: 443280
value: 2.87415E-15
type: LocalParameter

449939
stoichiometry: 1.0
species: 420066
type: SpeciesReference

419586
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

446310
stoichiometry: 1.0
species: 421206
type: SpeciesReference

444601
stoichiometry: 1.0
species: 419186
type: SpeciesReference

421986
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

419866
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

447569
stoichiometry: 1.0
species: 419266
type: SpeciesReference

450194
stoichiometry: 1.0
species: 418926
type: SpeciesReference

449482
units: 443196
value: 2.1E-15
type: LocalParameter

451576
local parameters: 449507
notes: k3*PP2A_slash_PP2A_minus_dephosph_minus_PP1_minus_I_star__slash_PP2A_minus_dephosph_minus_PP1_minus_I_star__cplx
type: KineticLaw

423945
kinetic law: 447024
product: 447011
reactant: 446998
reactant: 446985
notes: 10 x raise oct22 12 x oct 24, set k2 = 4 * k3
fast: false
reversible: true
type: Reaction

422425
kinetic law: 443510
product: 443498
reactant: 443486
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

444552
stoichiometry: 1.0
species: 419126
type: SpeciesReference

449404
units: 443196
value: 4.5E-16
type: LocalParameter

451989
stoichiometry: 1.0
species: 421426
type: SpeciesReference

452545
local parameters: 449554
local parameters: 449553
notes: k1*MAPK_slash_MAPK_minus_tyr*MKP3_slash_MKP_minus_3-k2*MKP3_slash_MKP_minus_3_slash_MKP3_minus_tyr_minus_deph_slash_MKP3_minus_tyr_minus_deph_cplx
type: KineticLaw

426165
kinetic law: 452834
product: 452822
reactant: 452810
reactant: 452798
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

444151
stoichiometry: 1.0
species: 421646
type: SpeciesReference

449483
units: 443196
value: 5.25E-16
type: LocalParameter

423905
kinetic law: 446937
product: 446925
reactant: 446913
notes: Time-course of 2 hours.
fast: false
reversible: true
type: Reaction

451294
stoichiometry: 1.0
species: 420866
type: SpeciesReference

450107
stoichiometry: 1.0
species: 422166
type: SpeciesReference

423365
kinetic law: 445720
product: 445708
reactant: 445696
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

447617
stoichiometry: 1.0
species: 418886
type: SpeciesReference

422426
kinetic law: 443559
product: 443547
reactant: 443535
reactant: 443522
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

444223
stoichiometry: 1.0
species: 419166
type: SpeciesReference

448028
stoichiometry: 1.0
species: 419386
type: SpeciesReference

449403
units: 443196
value: 1.8E-15
type: LocalParameter

451536
stoichiometry: 1.0
species: 420946
type: SpeciesReference

421646
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.08
initial amount: NaN
in compartment: 418386
type: Species

447497
stoichiometry: 1.0
species: 418866
type: SpeciesReference

449484
units: 443280
value: 5.147955E-16
type: LocalParameter

449647
stoichiometry: 1.0
species: 419926
type: SpeciesReference

449270
units: 443196
value: 1.5E-15
type: LocalParameter

446190
stoichiometry: 1.0
species: 421166
type: SpeciesReference

449402
units: 443280
value: 1.41426E-14
type: LocalParameter

448871
stoichiometry: 1.0
species: 419706
type: SpeciesReference

421906
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

445865
local parameters: 449254
local parameters: 449251
notes: kf*Ca^2*PP2B_slash_CaNAB_minus_Ca2-kb*CaNAB_minus_Ca4
type: KineticLaw

449271
units: 443280
value: 8.1E-14
type: LocalParameter

449485
units: 443196
value: 2.1E-15
type: LocalParameter

422325
constant: false
boundary condition: true
has only substance units: false
initial concentration: 0.0934
initial amount: NaN
in compartment: 418386
type: Species

445046
local parameters: 449182
local parameters: 449179
notes: kf*EGFR_slash_L_dot_EGFR-kb*EGFR_slash_Internal_L_dot_EGFR
type: KineticLaw

445468
stoichiometry: 1.0
species: 420346
type: SpeciesReference

444986
stoichiometry: 1.0
species: 420126
type: SpeciesReference

449569
units: 443196
value: 2.4E-14
type: LocalParameter

450472
stoichiometry: 1.0
species: 420506
type: SpeciesReference

419526
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

449078
units: 443196
value: 0.0
type: LocalParameter

448100
stoichiometry: 1.0
species: 419406
type: SpeciesReference

445576
stoichiometry: 1.0
species: 420746
type: SpeciesReference

423585
kinetic law: 446250
product: 446238
reactant: 446226
reactant: 446214
fast: false
reversible: true
type: Reaction

446395
local parameters: 449298
local parameters: 449295
notes: kf*PKA_minus_active*PKA_slash_PKA_minus_inhibitor-kb*PKA_slash_inhibited_minus_PKA
type: KineticLaw

421686
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

449034
units: 443196
value: 7.5E-16
type: LocalParameter

449373
units: 443280
value: 2.925045E-15
type: LocalParameter

447412
local parameters: 449370
local parameters: 449369
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

449079
units: 443280
value: 4.499955E-15
type: LocalParameter

452122
stoichiometry: 1.0
species: 421286
type: SpeciesReference

424565
kinetic law: 448544
product: 448532
product: 448520
reactant: 448508
fast: false
reversible: false
type: Reaction

444042
local parameters: 449094
local parameters: 449091
notes: kf*G_star_GTP*PLCbeta_slash_PLC_minus_Ca-kb*PLCbeta_slash_PLC_minus_Ca_minus_Gq
type: KineticLaw

449035
units: 443280
value: 1.1999745E-17
type: LocalParameter

420026
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.166666666666667
initial amount: NaN
in compartment: 418386
type: Species

423545
kinetic law: 446154
product: 446142
reactant: 446130
reactant: 446118
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

447132
stoichiometry: 1.0
species: 418686
type: SpeciesReference

446901
local parameters: 449346
local parameters: 449343
notes: kf*PKM_slash_Ca_detector*Ca^2-kb*PKM_slash_Ca_dot_detector_complex
type: KineticLaw

421606
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

453171
stoichiometry: 1.0
species: 422325
type: SpeciesReference

452955
stoichiometry: 1.0
species: 419686
type: SpeciesReference

425825
kinetic law: 452013
product: 452001
product: 451989
reactant: 451977
fast: false
reversible: false
type: Reaction

445973
stoichiometry: 1.0
species: 420746
type: SpeciesReference

425365
kinetic law: 450897
product: 450885
product: 450873
reactant: 450861
fast: false
reversible: false
type: Reaction

452653
stoichiometry: 1.0
species: 421806
type: SpeciesReference

444370
local parameters: 449122
local parameters: 449119
notes: kf*G_star_GTP-kb*G_star_GDP
type: KineticLaw

422286
constant: false
boundary condition: true
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

418666
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

MODEL9089538076
species: 419666
species: 418846
species: 421906
species: 422265
units def: 443280
species: 418866
species: 421966
species: 419826
reaction: 423925
reaction: 426425
species: 422086
reaction: 423445
species: 419846
reaction: 425025
reaction: 422765
species: 421346
reaction: 425145
species: 419726
species: 420786
species: 421546
reaction: 425705
species: 420466
species: 419566
species: 418786
species: 420666
species: 422246
species: 419026
species: 420506
reaction: 422665
species: 420166
reaction: 425485
reaction: 423385
species: 421186
reaction: 424005
reaction: 424765
species: 420186
reaction: 426105
reaction: 422985
species: 419486
reaction: 424485
species: 421206
reaction: 425365
species: 420366
reaction: 422465
reaction: 423126
reaction: 425925
reaction: 425865
species: 419366
species: 420566
reaction: 425285
reaction: 426205
species: 418946
species: 421486
reaction: 423865
reaction: 424585
reaction: 426325
reaction: 424845
species: 418486
species: 420686
species: 420886
reaction: 424405
area units: area
reaction: 422386
type: SBMLModel
reaction: 423325
reaction: 422405
reaction: 423085
reaction: 422685
species: 422126
reaction: 424425
reaction: 423065
reaction: 426165
species: 419466
species: 420946
reaction: 426125
reaction: 423185
reaction: 422566
reaction: 425905
reaction: 425565
reaction: 422725

443631
stoichiometry: 1.0
species: 418606
type: SpeciesReference

450218
local parameters: 449459
local parameters: 449458
notes: kcat*PLC_g_slash_Ca_dot_PLC_g_star_*PIP2/(Km+PIP2)
type: KineticLaw

426405
kinetic law: 453424
product: 453412
reactant: 453399
reactant: 453387
fast: false
reversible: true
type: Reaction

449376
units: 443196
value: 6.0E-14
type: LocalParameter

449162
units: 443196
value: 0.0
type: LocalParameter

453448
stoichiometry: 1.0
species: 421966
type: SpeciesReference

444199
stoichiometry: 1.0
species: 419146
type: SpeciesReference

451602
stoichiometry: 1.0
species: 420966
type: SpeciesReference

450327
stoichiometry: 1.0
species: 420366
type: SpeciesReference

449560
units: 443196
value: 2.4E-14
type: LocalParameter

443862
stoichiometry: 1.0
species: 418606
type: SpeciesReference

420826
constant: false
boundary condition: false
has only substance units: false
initial concentration: 1.8
initial amount: NaN
in compartment: 418386
type: Species

450364
local parameters: 449464
local parameters: 449463
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

449074
units: 443196
value: 1.5E-16
type: LocalParameter

422805
kinetic law: 444474
product: 444461
reactant: 444448
reactant: 444435
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

449038
units: 443196
value: 1.29522E-14
type: LocalParameter

422745
kinetic law: 444333
product: 444320
reactant: 444308
reactant: 444296
notes: kf == kg3 = 1e-5 /cell/sec. As usual, there is no back-reaction kb = 0
fast: false
reversible: true
type: Reaction

453063
stoichiometry: 1.0
species: 422325
type: SpeciesReference

425405
kinetic law: 450993
product: 450981
product: 450969
reactant: 450957
fast: false
reversible: false
type: Reaction

446419
stoichiometry: 1.0
species: 421326
type: SpeciesReference

449163
units: 443280
value: 2.99997E-13
type: LocalParameter

449377
units: 443196
value: 1.5E-14
type: LocalParameter

448653
stoichiometry: 1.0
species: 419326
type: SpeciesReference

448256
local parameters: 449401
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

451796
stoichiometry: 1.0
species: 421286
type: SpeciesReference

422705
kinetic law: 444235
product: 444223
reactant: 444211
reactant: 444199
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

446612
stoichiometry: 1.0
species: 421446
type: SpeciesReference

420446
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

451832
stoichiometry: 1.0
species: 422205
type: SpeciesReference

421086
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

422126
constant: true
boundary condition: true
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

446286
stoichiometry: 1.0
species: 421206
type: SpeciesReference

422685
kinetic law: 444187
product: 444175
reactant: 444163
reactant: 444151
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

449075
units: 443196
value: 2.55E-16
type: LocalParameter

423725
kinetic law: 446576
product: 446563
reactant: 446551
reactant: 446539
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

447521
stoichiometry: 1.0
species: 418866
type: SpeciesReference

450083
stoichiometry: 1.0
species: 420046
type: SpeciesReference

449039
units: 443196
value: 1.90575E-15
type: LocalParameter

447011
stoichiometry: 1.0
species: 418646
type: SpeciesReference

449378
units: 443280
value: 2.925045E-15
type: LocalParameter

447956
stoichiometry: 1.0
species: 419006
type: SpeciesReference

449757
local parameters: 449442
local parameters: 449441
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

421006
constant: false
boundary condition: false
has only substance units: false
initial concentration: 1.0
initial amount: NaN
in compartment: 418386
type: Species

452497
local parameters: 449552
notes: k3*MKP3_slash_MKP_minus_3_slash_MKP3_minus_thr_minus_deph_slash_MKP3_minus_thr_minus_deph_cplx
type: KineticLaw

446359
stoichiometry: 1.0
species: 419886
type: SpeciesReference

449562
units: 443280
value: 9.000045E-15
type: LocalParameter

444333
local parameters: 449118
local parameters: 449115
notes: kf*G_star_GDP*BetaGamma-kb*Gq_slash_G_minus_GDP
type: KineticLaw

418786
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

445420
stoichiometry: 1.0
species: 420426
type: SpeciesReference

449379
units: 443196
value: 6.0E-14
type: LocalParameter

424665
kinetic law: 448786
product: 448774
reactant: 448762
reactant: 448750
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

445154
stoichiometry: 1.0
species: 420226
type: SpeciesReference

420866
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

453111
stoichiometry: 1.0
species: 421906
type: SpeciesReference

443522
stoichiometry: 1.0
species: 418526
type: SpeciesReference

424625
kinetic law: 448690
product: 448678
reactant: 448665
reactant: 448653
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

451306
stoichiometry: 1.0
species: 422305
type: SpeciesReference

448196
stoichiometry: 1.0
species: 419466
type: SpeciesReference

449561
units: 443196
value: 6.0E-15
type: LocalParameter

418746
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

446998
stoichiometry: 1.0
species: 418626
type: SpeciesReference

421046
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

449166
units: 443196
value: 1.5E-15
type: LocalParameter

419426
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

452424
stoichiometry: 1.0
species: 421726
type: SpeciesReference

453015
stoichiometry: 1.0
species: 421886
type: SpeciesReference

423025
kinetic law: 444974
product: 444962
reactant: 444950
reactant: 444938
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

452725
stoichiometry: 1.0
species: 421826
type: SpeciesReference

448556
stoichiometry: 1.0
species: 419426
type: SpeciesReference

418446
constant: false
boundary condition: false
has only substance units: false
initial concentration: 1.38955555555556E-17
initial amount: NaN
in compartment: 418386
type: Species

445600
stoichiometry: 1.0
species: 420746
type: SpeciesReference

449115
units: 443280
value: 9.000045E-15
type: LocalParameter

449449
units: 443196
value: 3.0E-17
type: LocalParameter

452871
stoichiometry: 1.0
species: 422325
type: SpeciesReference

446660
local parameters: 449322
local parameters: 449319
notes: kf*AC_slash_cAMP_minus_PDE_star_-kb*AC_slash_cAMP_minus_PDE
type: KineticLaw

449155
units: 443196
value: 1.5E-19
type: LocalParameter

418406
constant: true
size: 2.5E-21
spatial dimensions: 3.0
type: Compartment

446467
stoichiometry: 1.0
species: 421386
type: SpeciesReference

422585
kinetic law: 443958
product: 443946
reactant: 443934
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

449448
units: 443196
value: 1.2E-16
type: LocalParameter

450035
stoichiometry: 1.0
species: 420086
type: SpeciesReference

443340
exponent: 1.0
scale: -6
multipler: 1.0
kind: MOLE
type: SBMLUnit

447291
stoichiometry: 1.0
species: 418746
type: SpeciesReference

449158
units: 443196
value: 0.0
type: LocalParameter

443449
stoichiometry: 1.0
species: 418426
type: SpeciesReference

419326
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

449222
units: 443196
value: 0.0
type: LocalParameter

447060
stoichiometry: 1.0
species: 418626
type: SpeciesReference

420226
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

443172
exponent: -1.0
scale: 0
multipler: 1.0
kind: LITRE
type: SBMLUnit

449380
units: 443196
value: 1.5E-14
type: LocalParameter

451042
local parameters: 449488
local parameters: 449487
notes: k1*CaMKII_slash_CaMKII_minus_thr286*PP1_minus_active-k2*PP1_minus_active_slash_Deph_thr286b_slash_Deph_thr286b_cplx
type: KineticLaw

445757
stoichiometry: 1.0
species: 420866
type: SpeciesReference

421726
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.02
initial amount: NaN
in compartment: 418386
type: Species

448932
local parameters: 449425
notes: k3*Ras_slash_GEF_star__slash_GEF_star__minus_act_minus_ras_slash_GEF_star__minus_act_minus_ras_cplx
type: KineticLaw

445118
stoichiometry: 1.0
species: 420186
type: SpeciesReference

449509
units: 443280
value: 5.13E-17
type: LocalParameter

444650
stoichiometry: 1.0
species: 419266
type: SpeciesReference

420126
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

419366
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

447340
stoichiometry: 1.0
species: 418586
type: SpeciesReference

443413
stoichiometry: 1.0
species: 418426
type: SpeciesReference

450532
stoichiometry: 1.0
species: 422286
type: SpeciesReference

425765
kinetic law: 451869
modifier: 451857
product: 451845
reactant: 451832
fast: false
reversible: false
type: Reaction

449223
units: 443232
value: 1.08000135E-13
type: LocalParameter

449118
units: 443196
value: 0.0
type: LocalParameter

445949
stoichiometry: 1.0
species: 421066
type: SpeciesReference

421506
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

422285
constant: false
boundary condition: true
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

421486
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

449382
units: 443196
value: 6.0E-14
type: LocalParameter

447738
stoichiometry: 1.0
species: 418846
type: SpeciesReference

444500
stoichiometry: 1.0
species: 419086
type: SpeciesReference

449975
stoichiometry: 1.0
species: 420326
type: SpeciesReference

449043
units: 443196
value: 1.5E-15
type: LocalParameter

451688
stoichiometry: 1.0
species: 422205
type: SpeciesReference

444127
stoichiometry: 1.0
species: 419046
type: SpeciesReference

449445
units: 443280
value: 2.97E-16
type: LocalParameter

449119
units: 443196
value: 1.995E-17
type: LocalParameter

421946
constant: false
boundary condition: false
has only substance units: false
initial concentration: 1.0
initial amount: NaN
in compartment: 418386
type: Species

446576
local parameters: 449314
local parameters: 449311
notes: kf*Gs_minus_alpha*AC_slash_AC1-kb*AC_slash_AC1_minus_Gs
type: KineticLaw

449159
units: 443196
value: 1.5E-16
type: LocalParameter

452593
local parameters: 449555
notes: k3*MKP3_slash_MKP_minus_3_slash_MKP3_minus_tyr_minus_deph_slash_MKP3_minus_tyr_minus_deph_cplx
type: KineticLaw

449381
units: 443280
value: 2.925045E-14
type: LocalParameter

449042
units: 443196
value: 5.2539E-15
type: LocalParameter

421546
constant: false
boundary condition: false
has only substance units: false
initial concentration: 2.0
initial amount: NaN
in compartment: 418386
type: Species

447304
stoichiometry: 1.0
species: 418766
type: SpeciesReference

451138
local parameters: 449494
local parameters: 449491
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

444435
stoichiometry: 1.0
species: 422106
type: SpeciesReference

449331
units: 443280
value: 3.75003E-19
type: LocalParameter

451450
stoichiometry: 1.0
species: 420826
type: SpeciesReference

424285
kinetic law: 447859
product: 447846
product: 447834
product: 447822
reactant: 447810
fast: false
reversible: false
type: Reaction

423325
kinetic law: 445636
product: 445624
reactant: 445612
reactant: 445600
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

450933
stoichiometry: 1.0
species: 420626
type: SpeciesReference

448364
stoichiometry: 1.0
species: 419266
type: SpeciesReference

426225
kinetic law: 452979
product: 452967
product: 452955
reactant: 452943
fast: false
reversible: false
type: Reaction

452025
stoichiometry: 1.0
species: 421286
type: SpeciesReference

424345
kinetic law: 448016
product: 448004
reactant: 447992
reactant: 447980
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

449384
units: 443280
value: 3.78E-15
type: LocalParameter

452617
stoichiometry: 1.0
species: 421786
type: SpeciesReference

447181
stoichiometry: 1.0
species: 422066
type: SpeciesReference

422245
notes: Amino acids for MKP3 synthesis.
constant: true
boundary condition: true
has only substance units: false
initial concentration: 1.0
initial amount: NaN
in compartment: 418386
type: Species

449443
units: 443196
value: 1.35E-14
type: LocalParameter

449330
units: 443196
value: 1.5E-13
type: LocalParameter

422205
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: 418386
type: Species

451006
stoichiometry: 1.0
species: 420426
type: SpeciesReference

425985
kinetic law: 452400
product: 452388
product: 452376
reactant: 452364
fast: false
reversible: false
type: Reaction

422965
kinetic law: 444842
product: 444830
reactant: 444818
notes: Assume a reasonably good rate for dephosphorylating it, 1/sec
fast: false
reversible: true
type: Reaction

445299
stoichiometry: 1.0
species: 420286
type: SpeciesReference

445202
stoichiometry: 1.0
species: 420246
type: SpeciesReference

444487
stoichiometry: 1.0
species: 419206
type: SpeciesReference

449383
units: 443196
value: 1.5E-14
type: LocalParameter

451174
stoichiometry: 1.0
species: 422305
type: SpeciesReference

447230
stoichiometry: 1.0
species: 418726
type: SpeciesReference

426265
kinetic law: 453075
product: 453063
product: 453051
reactant: 453039
fast: false
reversible: false
type: Reaction

422206
constant: true
boundary condition: true
has only substance units: false
initial concentration: 0.2
initial amount: NaN
in compartment: 418386
type: Species

452991
stoichiometry: 1.0
species: 420726
type: SpeciesReference

424305
kinetic law: 447907
product: 447895
reactant: 447883
reactant: 447871
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

449442
units: 443196
value: 5.4E-14
type: LocalParameter

419826
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

424245
kinetic law: 447750
product: 447738
product: 447726
reactant: 447714
fast: false
reversible: false
type: Reaction

450606
local parameters: 449471
notes: k3*CaMKII_slash_tot_autonomous_CaMKII_slash_auton_286_slash_auton_286_cplx
type: KineticLaw

451246
stoichiometry: 1.0
species: 420806
type: SpeciesReference

449441
units: 443280
value: 9.000045E-15
type: LocalParameter

423985
kinetic law: 447120
product: 447108
reactant: 447096
reactant: 447084
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

421326
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.02
initial amount: NaN
in compartment: 418386
type: Species

447665
stoichiometry: 1.0
species: 420246
type: SpeciesReference

449501
units: 443196
value: 5.1E-16
type: LocalParameter

450981
stoichiometry: 1.0
species: 420546
type: SpeciesReference

446841
stoichiometry: 1.0
species: 422226
type: SpeciesReference

425945
kinetic law: 452304
product: 452292
product: 452280
reactant: 452268
fast: false
reversible: false
type: Reaction

449491
units: 443280
value: 5.004045E-16
type: LocalParameter

449866
stoichiometry: 1.0
species: 420006
type: SpeciesReference

418626
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

419006
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

449400
units: 443196
value: 1.8E-15
type: LocalParameter

419046
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

445190
stoichiometry: 1.0
species: 420186
type: SpeciesReference

452280
stoichiometry: 1.0
species: 421426
type: SpeciesReference

449440
units: 443196
value: 1.35E-14
type: LocalParameter

449502
units: 443280
value: 5.94E-15
type: LocalParameter

449335
units: 443196
value: 1.5E-21
type: LocalParameter

422246
constant: true
boundary condition: true
has only substance units: false
initial concentration: 1.0
initial amount: NaN
in compartment: 418386
type: Species

449490
stoichiometry: 1.0
species: 419906
type: SpeciesReference

452509
stoichiometry: 1.0
species: 419346
type: SpeciesReference

452388
stoichiometry: 1.0
species: 421686
type: SpeciesReference

449401
units: 443196
value: 4.5E-16
type: LocalParameter

444722
stoichiometry: 1.0
species: 419626
type: SpeciesReference

451342
stoichiometry: 1.0
species: 419606
type: SpeciesReference

418372
constant: true
size: 1.0E-18
spatial dimensions: 3.0
type: Compartment

424885
kinetic law: 449708
product: 449696
product: 449683
reactant: 449671
fast: false
reversible: false
type: Reaction

420526
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

425325
kinetic law: 450799
product: 450787
product: 450775
reactant: 450763
fast: false
reversible: false
type: Reaction

448076
stoichiometry: 1.0
species: 419346
type: SpeciesReference

444698
stoichiometry: 1.0
species: 419066
type: SpeciesReference

447388
stoichiometry: 1.0
species: 418786
type: SpeciesReference

424525
kinetic law: 448448
product: 448436
product: 448424
reactant: 448412
fast: false
reversible: false
type: Reaction

446142
stoichiometry: 1.0
species: 421146
type: SpeciesReference

419686
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

449334
units: 443196
value: 1.5E-18
type: LocalParameter

448617
stoichiometry: 1.0
species: 419286
type: SpeciesReference

444878
stoichiometry: 1.0
species: 419846
type: SpeciesReference

448762
stoichiometry: 1.0
species: 419626
type: SpeciesReference

449333
stoichiometry: 1.0
species: 419666
type: SpeciesReference

443754
local parameters: 449066
local parameters: 449063
notes: kf*DAG*PLA2_slash_PLA2_minus_Ca_star_-kb*PLA2_slash_DAG_minus_Ca_minus_PLA2_star_
type: KineticLaw

449110
units: 443196
value: 1.5E-14
type: LocalParameter

449500
units: 443196
value: 2.04E-15
type: LocalParameter

445082
stoichiometry: 1.0
species: 419986
type: SpeciesReference

443716
stoichiometry: 1.0
species: 418566
type: SpeciesReference

445311
stoichiometry: 1.0
species: 420326
type: SpeciesReference

448472
stoichiometry: 1.0
species: 419506
type: SpeciesReference

453339
stoichiometry: 1.0
species: 421986
type: SpeciesReference

452762
stoichiometry: 1.0
species: 419266
type: SpeciesReference

449505
units: 443280
value: 5.94E-15
type: LocalParameter

449111
units: 443196
value: 1.5E-19
type: LocalParameter

420386
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

443389
local parameters: 449034
local parameters: 449031
notes: kf*PKC_slash_PKC_minus_cytosolic*Ca-kb*PKC_slash_PKC_minus_Ca
type: KineticLaw

452834
local parameters: 449563
local parameters: 449562
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

450873
stoichiometry: 1.0
species: 420346
type: SpeciesReference

421126
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 418386
type: Species

424845
kinetic law: 449611
product: 449599
product: 449550
reactant: 449490
fast: false
reversible: false
type: Reaction

425065
type: Reaction
fast: false
kinetic law: 450157
modifier: 450145
reversible: false
product: 450120
product: 450132
reactant: 450107
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.

451090
local parameters: 449489
notes: k3*PP1_minus_active_slash_Deph_thr286b_slash_Deph_thr286b_cplx
type: KineticLaw

424725
kinetic law: 448932
product: 448919
product: 448907
reactant: 448895
fast: false
reversible: false
type: Reaction

446106
local parameters: 449274
local parameters: 449271
notes: kf*PKA_slash_R2C2*cAMP-kb*PKA_slash_R2C2_minus_cAMP
type: KineticLaw

444830
stoichiometry: 1.0
species: 419786
type: SpeciesReference

445901
stoichiometry: 1.0
species: 421026
type: SpeciesReference

425025
kinetic law: 450047
product: 450035
reactant: 450023
reactant: 450011
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

449339
units: 443196
value: 7.5E-19
type: LocalParameter

449506
units: 443196
value: 3.75E-14
type: LocalParameter

445528
stoichiometry: 1.0
species: 420766
type: SpeciesReference

424805
kinetic law: 449321
product: 449308
product: 449296
reactant: 449284
fast: false
reversible: false
type: Reaction

426025
kinetic law: 452497
product: 452484
product: 452472
reactant: 452460
fast: false
reversible: false
type: Reaction

447774
stoichiometry: 1.0
species: 418966
type: SpeciesReference

449507
units: 443196
value: 9.0E-15
type: LocalParameter

451869
local parameters: 449525
local parameters: 449522
notes: kcat*AC_slash_AC1_minus_Gs*AC_slash_ATP/(Km+AC_slash_ATP)
type: KineticLaw

452170
stoichiometry: 1.0
species: 421566
type: SpeciesReference

449503
units: 443196
value: 3.75E-14
type: LocalParameter

449226
units: 443196
value: 1.08E-13
type: LocalParameter

449338
units: 443196
value: 1.5E-18
type: LocalParameter

445648
stoichiometry: 1.0
species: 420726
type: SpeciesReference

450254
stoichiometry: 1.0
species: 420466
type: SpeciesReference

452231
stoichiometry: 1.0
species: 421586
type: SpeciesReference

422166
constant: true
boundary condition: true
has only substance units: false
initial concentration: 10.0
initial amount: NaN
in compartment: 418386
type: Species

449267
units: 443280
value: 9.000045E-13
type: LocalParameter

450714
stoichiometry: 1.0
species: 420406
type: SpeciesReference

448726
stoichiometry: 1.0
species: 419506
type: SpeciesReference

449114
units: 443280
value: 0.0
type: LocalParameter

449227
units: 443280
value: 5.4E-15
type: LocalParameter

449504
units: 443196
value: 9.0E-15
type: LocalParameter

445250
stoichiometry: 1.0
species: 421646
type: SpeciesReference

445696
stoichiometry: 1.0
species: 420706
type: SpeciesReference

443826
stoichiometry: 1.0
species: 418786
type: SpeciesReference

446033
stoichiometry: 1.0
species: 420966
type: SpeciesReference

443970
stoichiometry: 1.0
species: 418566
type: SpeciesReference

444018
stoichiometry: 1.0
species: 418966
type: SpeciesReference

449266
units: 443196
value: 1.5E-15
type: LocalParameter