480197
stoichiometry: 1.0
species: 574852
type: SpeciesReference

575531
kinetic law: 480074
product: 480062
reactant: 480050
reactant: 480038
notes: Raise kf from 1.667e-10 to 2e-10 to get better match to data.
fast: false
reversible: true
type: Reaction

479963
stoichiometry: 1.0
species: 574051
type: SpeciesReference

481556
local parameters: 274527
local parameters: 274525
notes: k1*MAPK_slash_MAPK_minus_tyr*MAPK_slash_MAPKK_star_-k2*MAPK_slash_MAPKK_star__slash_MAPKKthr_slash_MAPKKthr_cplx
type: KineticLaw

480245
stoichiometry: 1.0
species: 574111
type: SpeciesReference

481216
local parameters: 274508
notes: k3*PLA2_slash_PIP2_minus_Ca_minus_PLA2_star__slash_kenz_slash_kenz_cplx
type: KineticLaw

480718
stoichiometry: 2.0
species: 574852
type: SpeciesReference

274491
units: 479585
value: 1.257E-12
type: LocalParameter

576871
kinetic law: 483249
product: 483237
product: 483225
reactant: 483213
fast: false
reversible: false
type: Reaction

274535
units: 479672
value: 1.18513155294E-12
type: LocalParameter

480001
stoichiometry: 1.0
species: 574071
type: SpeciesReference

274575
units: 479672
value: 7.5420478917E-13
type: LocalParameter

480305
stoichiometry: 1.0
species: 574211
type: SpeciesReference

575511
kinetic law: 480025
product: 480013
reactant: 480001
notes: Initial basal levels were set by kf = 1, kb = 20. In model, though, the basal levels of PKC activity are higher.
fast: false
reversible: true
type: Reaction

483030
stoichiometry: 1.0
species: 574451
type: SpeciesReference

576891
kinetic law: 483297
product: 483285
reactant: 483273
reactant: 483261
fast: false
reversible: true
type: Reaction

575391
kinetic law: 479782
product: 479769
reactant: 479757
reactant: 479745
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

482766
local parameters: 274588
notes: k3*MAPK_star__slash_MAPK_star__slash_MAPK_star__cplx
type: KineticLaw

274585
units: 479672
value: 2.45122481664E-13
type: LocalParameter

481701
local parameters: 274533
notes: k3*MAPK_slash_Raf_minus_GTP_minus_Ras_slash_Raf_minus_GTP_minus_Ras_dot_1_slash_Raf_minus_GTP_minus_Ras_dot_1_cplx
type: KineticLaw

482391
stoichiometry: 1.0
species: 574351
type: SpeciesReference

482343
stoichiometry: 1.0
species: 574851
type: SpeciesReference

482247
stoichiometry: 1.0
species: 574811
type: SpeciesReference

480511
stoichiometry: 1.0
species: 574731
type: SpeciesReference

274522
units: 479585
value: 1.5084E-13
type: LocalParameter

274620
units: 479672
value: 2.40856349364E-13
type: LocalParameter

483382
stoichiometry: 1.0
species: 575151
type: SpeciesReference

574971
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 573851
type: Species

481568
stoichiometry: 1.0
species: 574511
type: SpeciesReference

575591
kinetic law: 480221
product: 480209
reactant: 480197
reactant: 480184
notes: Leslie and Channon BBA 1045 (1990) 261-270 fig6 pp267.
fast: false
reversible: true
type: Reaction

481980
stoichiometry: 1.0
species: 574591
type: SpeciesReference

274537
units: 479585
value: 1.5084E-13
type: LocalParameter

575691
kinetic law: 480451
product: 480439
reactant: 480427
reactant: 480415
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

481010
stoichiometry: 1.0
species: 574131
type: SpeciesReference

480791
local parameters: 274491
local parameters: 274489
notes: kf*CaM_slash_CaM_minus_TR2_minus_Ca2*Ca-kb*CaM_slash_CaM_minus_Ca3
type: KineticLaw

479866
local parameters: 274447
local parameters: 274446
notes: kf*PKC_slash_PKC_minus_Ca-kb*PKC_slash_PKC_minus_Ca_minus_memb_star_
type: KineticLaw

274523
units: 479585
value: 3.771E-14
type: LocalParameter

479951
local parameters: 274451
local parameters: 274450
notes: kf*PKC_slash_PKC_minus_Ca*AA-kb*PKC_slash_PKC_minus_Ca_minus_AA_star_
type: KineticLaw

480233
stoichiometry: 1.0
species: 575271
type: SpeciesReference

274533
units: 479585
value: 3.771E-14
type: LocalParameter

481120
local parameters: 274503
notes: k3*PLA2_slash_PIP2_minus_PLA2_star__slash_kenz_slash_kenz_cplx
type: KineticLaw

576091
kinetic law: 481361
product: 481349
reactant: 481337
reactant: 481325
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

480403
local parameters: 274472
local parameters: 274471
notes: kf*AA-kb*PLA2_slash_APC
type: KineticLaw

274573
units: 479585
value: 5.028E-13
type: LocalParameter

274587
units: 479585
value: 5.028E-12
type: LocalParameter

481993
local parameters: 274548
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

480317
local parameters: 274468
local parameters: 274466
notes: kf*temp_minus_PIP2*PLA2_slash_PLA2_minus_Ca_star_-kb*PLA2_slash_PIP2_minus_Ca_minus_PLA2_star_
type: KineticLaw

480013
stoichiometry: 1.0
species: 573971
type: SpeciesReference

574231
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 573851
type: Species

483055
local parameters: 274603
notes: k3*MKP_minus_1_slash_MKP1_minus_thr_minus_deph_slash_MKP1_minus_thr_minus_deph_cplx
type: KineticLaw

482331
local parameters: 274567
local parameters: 274565
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

482259
stoichiometry: 1.0
species: 574751
type: SpeciesReference

481229
stoichiometry: 1.0
species: 575251
type: SpeciesReference

480705
stoichiometry: 1.0
species: 575171
type: SpeciesReference

480086
stoichiometry: 1.0
species: 574071
type: SpeciesReference

481714
stoichiometry: 1.0
species: 574531
type: SpeciesReference

479878
stoichiometry: 1.0
species: 574011
type: SpeciesReference

574171
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 573851
type: Species

574211
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 573851
type: Species

576811
kinetic law: 483104
product: 483092
reactant: 483080
reactant: 483068
notes: See parent PPhosphatase2A for parms
fast: false
reversible: true
type: Reaction

274588
units: 479585
value: 1.257E-12
type: LocalParameter

575411
kinetic law: 479830
product: 479818
reactant: 479806
reactant: 479794
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

575611
kinetic law: 480269
product: 480257
reactant: 480245
reactant: 480233
fast: false
reversible: true
type: Reaction

574751
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.5
initial amount: NaN
in compartment: 573851
type: Species

480025
local parameters: 274455
local parameters: 274454
notes: kf*PKC_slash_PKC_minus_cytosolic-kb*PKC_slash_PKC_minus_basal_star_
type: KineticLaw

479757
stoichiometry: 1.0
species: 574852
type: SpeciesReference

481132
stoichiometry: 1.0
species: 575251
type: SpeciesReference

480415
stoichiometry: 1.0
species: 574331
type: SpeciesReference

482439
stoichiometry: 1.0
species: 574871
type: SpeciesReference

274525
units: 479672
value: 4.07263949946E-12
type: LocalParameter

480463
stoichiometry: 1.0
species: 574331
type: SpeciesReference

481481
stoichiometry: 1.0
species: 574451
type: SpeciesReference

482139
local parameters: 274557
local parameters: 274555
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

482742
stoichiometry: 1.0
species: 574331
type: SpeciesReference

480221
local parameters: 274463
local parameters: 274462
notes: kf*PLA2_slash_PLA2_minus_cytosolic*Ca-kb*PLA2_slash_PLA2_minus_Ca_star_
type: KineticLaw

479660
exponent: -1.0
scale: 0
multipler: 1.0
kind: SECOND
type: SBMLUnit

274545
units: 479672
value: 1.18513155294E-12
type: LocalParameter

274507
units: 479585
value: 1.81008E-11
type: LocalParameter

574771
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 573851
type: Species

483006
local parameters: 274602
local parameters: 274600
notes: k1*MAPK_star_*MKP_minus_1-k2*MKP_minus_1_slash_MKP1_minus_thr_minus_deph_slash_MKP1_minus_thr_minus_deph_cplx
type: KineticLaw

483080
stoichiometry: 1.0
species: 575071
type: SpeciesReference

479842
stoichiometry: 1.0
species: 573871
type: SpeciesReference

481543
stoichiometry: 1.0
species: 574511
type: SpeciesReference

575091
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 573851
type: Species

482778
stoichiometry: 1.0
species: 574371
type: SpeciesReference

480938
stoichiometry: 1.0
species: 575251
type: SpeciesReference

274610
units: 479672
value: 2.40856349364E-13
type: LocalParameter

482427
local parameters: 274572
local parameters: 274570
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

575311
notes: Peak IP3 is perhaps 15 uM, basal <= 0.2 uM.
constant: true
boundary condition: true
has only substance units: false
initial concentration: 0.730005303632989
initial amount: NaN
in compartment: 573851
type: Species

274527
units: 479585
value: 1.5084E-13
type: LocalParameter

575711
kinetic law: 480487
product: 480475
reactant: 480463
fast: false
reversible: true
type: Reaction

483128
stoichiometry: 1.0
species: 574351
type: SpeciesReference

576071
kinetic law: 481313
product: 481301
product: 481289
reactant: 481277
fast: false
reversible: false
type: Reaction

575451
kinetic law: 479903
product: 479890
reactant: 479878
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

482223
stoichiometry: 1.0
species: 574811
type: SpeciesReference

274625
units: 479585
value: 3.0168E-12
type: LocalParameter

576951
kinetic law: 483442
product: 483430
product: 483418
reactant: 483406
fast: false
reversible: false
type: Reaction

480172
local parameters: 274461
local parameters: 274460
notes: kf*PKC_slash_PKC_minus_DAG*AA-kb*PKC_slash_PKC_minus_DAG_minus_AA
type: KineticLaw

575651
kinetic law: 480367
product: 480355
reactant: 480342
reactant: 480330
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

576131
kinetic law: 481457
product: 481445
reactant: 481433
reactant: 481421
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

576371
kinetic law: 482042
product: 482030
reactant: 482018
reactant: 482006
fast: false
reversible: true
type: Reaction

480427
stoichiometry: 1.0
species: 574852
type: SpeciesReference

574371
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 573851
type: Species

481144
stoichiometry: 1.0
species: 574211
type: SpeciesReference

274613
units: 479585
value: 7.542E-13
type: LocalParameter

481493
stoichiometry: 1.0
species: 574471
type: SpeciesReference

482754
stoichiometry: 1.0
species: 574951
type: SpeciesReference

274597
units: 479585
value: 2.0112E-12
type: LocalParameter

480451
local parameters: 274474
local parameters: 274473
notes: kf*PLA2_slash_PLA2_star_*Ca-kb*PLA2_slash_PLA2_star__minus_Ca
type: KineticLaw

274449
units: 479585
value: 1.257E-14
type: LocalParameter

575111
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 573851
type: Species

479769
stoichiometry: 1.0
species: 573871
type: SpeciesReference

483042
stoichiometry: 1.0
species: 575011
type: SpeciesReference

479709
exponent: -1.0
scale: 0
multipler: 1.0
kind: SECOND
type: SBMLUnit

482403
stoichiometry: 1.0
species: 575351
type: SpeciesReference

274548
units: 479585
value: 3.771E-14
type: LocalParameter

480099
stoichiometry: 1.0
species: 575291
type: SpeciesReference

274547
units: 479585
value: 1.5084E-13
type: LocalParameter

274528
units: 479585
value: 3.771E-14
type: LocalParameter

483018
stoichiometry: 1.0
species: 575051
type: SpeciesReference

574331
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 573851
type: Species

274448
units: 479585
value: 1.257E-13
type: LocalParameter

274577
units: 479585
value: 2.0112E-12
type: LocalParameter

575011
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0240002651816494
initial amount: NaN
in compartment: 573851
type: Species

274538
units: 479585
value: 3.771E-14
type: LocalParameter

274557
units: 479585
value: 1.0056E-14
type: LocalParameter

482091
local parameters: 274553
notes: k3*Ras_slash_inact_minus_GEF_slash_basal_GEF_activity_slash_basal_GEF_activity_cplx
type: KineticLaw

274612
units: 479585
value: 3.0168E-12
type: LocalParameter

481204
stoichiometry: 1.0
species: 574211
type: SpeciesReference

480926
local parameters: 274497
local parameters: 274496
notes: kf*Ca_input-kb*Ca
type: KineticLaw

274598
units: 479585
value: 5.028E-13
type: LocalParameter

574031
constant: false
boundary condition: false
has only substance units: false
initial concentration: 1.16100503845134E-16
initial amount: NaN
in compartment: 573851
type: Species

482415
stoichiometry: 1.0
species: 574871
type: SpeciesReference

479854
stoichiometry: 1.0
species: 573931
type: SpeciesReference

576271
kinetic law: 481799
product: 481786
product: 481774
reactant: 481762
fast: false
reversible: false
type: Reaction

576671
kinetic law: 482766
product: 482754
product: 482742
reactant: 482730
fast: false
reversible: false
type: Reaction

481059
stoichiometry: 1.0
species: 574191
type: SpeciesReference

576331
kinetic law: 481944
product: 481932
reactant: 481920
reactant: 481908
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

576171
kinetic law: 481556
product: 481543
reactant: 481531
reactant: 481519
notes: Rate consts same as for MAPKKtyr.
fast: false
reversible: true
type: Reaction

480038
stoichiometry: 1.0
species: 574091
type: SpeciesReference

573839
constant: true
size: 1.0E-18
spatial dimensions: 3.0
type: Compartment

576691
kinetic law: 482814
product: 482802
reactant: 482790
reactant: 482778
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

482560
stoichiometry: 1.0
species: 575351
type: SpeciesReference

574131
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 573851
type: Species

274518
units: 479585
value: 1.5084E-11
type: LocalParameter

575051
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 573851
type: Species

480184
stoichiometry: 1.0
species: 574111
type: SpeciesReference

574431
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 573851
type: Species

483092
stoichiometry: 1.0
species: 575091
type: SpeciesReference

274508
units: 479585
value: 4.5252E-12
type: LocalParameter

482235
local parameters: 274562
local parameters: 274560
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

274578
units: 479585
value: 5.028E-13
type: LocalParameter

483116
stoichiometry: 1.0
species: 575091
type: SpeciesReference

481192
stoichiometry: 1.0
species: 574091
type: SpeciesReference

483418
stoichiometry: 1.0
species: 574371
type: SpeciesReference

575191
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 573851
type: Species

274558
units: 479585
value: 2.514E-15
type: LocalParameter

483406
stoichiometry: 1.0
species: 575151
type: SpeciesReference

574791
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.01
initial amount: NaN
in compartment: 573851
type: Species

481096
stoichiometry: 1.0
species: 574091
type: SpeciesReference

482079
stoichiometry: 1.0
species: 574651
type: SpeciesReference

274517
units: 479585
value: 6.0336E-11
type: LocalParameter

480050
stoichiometry: 1.0
species: 574071
type: SpeciesReference

274595
units: 479672
value: 1.88553567366E-11
type: LocalParameter

480914
stoichiometry: 1.0
species: 574852
type: SpeciesReference

274502
units: 479585
value: 5.550912E-12
type: LocalParameter

274615
units: 479672
value: 2.40856349364E-13
type: LocalParameter

482886
stoichiometry: 1.0
species: 575011
type: SpeciesReference

483176
stoichiometry: 1.0
species: 575071
type: SpeciesReference

482958
local parameters: 274598
notes: k3*MKP_minus_1_slash_MKP1_minus_tyr_minus_deph_slash_MKP1_minus_tyr_minus_deph_cplx
type: KineticLaw

479818
stoichiometry: 1.0
species: 574011
type: SpeciesReference

576751
kinetic law: 482958
product: 482946
product: 482934
reactant: 482922
fast: false
reversible: false
type: Reaction

576771
kinetic law: 483006
product: 482994
reactant: 482982
reactant: 482970
notes: See MKP1-tyr-deph
fast: false
reversible: true
type: Reaction

480645
local parameters: 274484
local parameters: 274483
notes: kf*Ras_slash_GAP_star_-kb*Ras_slash_GAP
type: KineticLaw

481835
stoichiometry: 1.0
species: 574611
type: SpeciesReference

479733
exponent: 1.0
scale: -6
multipler: 1.0
kind: MOLE
type: SBMLUnit

481908
stoichiometry: 1.0
species: 574531
type: SpeciesReference

481156
stoichiometry: 1.0
species: 574231
type: SpeciesReference

480439
stoichiometry: 1.0
species: 574291
type: SpeciesReference

482271
stoichiometry: 1.0
species: 574791
type: SpeciesReference

274501
units: 479672
value: 3.4693135893E-13
type: LocalParameter

274618
units: 479585
value: 7.542E-13
type: LocalParameter

576471
kinetic law: 482283
product: 482271
product: 482259
reactant: 482247
fast: false
reversible: false
type: Reaction

481677
stoichiometry: 1.0
species: 574531
type: SpeciesReference

274505
units: 479672
value: 1.13128348302E-12
type: LocalParameter

482067
stoichiometry: 1.0
species: 574731
type: SpeciesReference

274515
units: 479672
value: 3.77097654438E-12
type: LocalParameter

482670
local parameters: 274583
notes: k3*PKC_minus_active_slash_PKC_minus_act_minus_GEF_slash_PKC_minus_act_minus_GEF_cplx
type: KineticLaw

482379
local parameters: 274568
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

482211
stoichiometry: 1.0
species: 574791
type: SpeciesReference

480902
stoichiometry: 1.0
species: 575331
type: SpeciesReference

274593
units: 479585
value: 1.257E-12
type: LocalParameter

480962
stoichiometry: 1.0
species: 574151
type: SpeciesReference

576411
kinetic law: 482139
product: 482127
reactant: 482115
reactant: 482103
notes: Kinetics same as GEF-bg-act-ras
fast: false
reversible: true
type: Reaction

576451
kinetic law: 482235
product: 482223
reactant: 482211
reactant: 482199
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

481046
stoichiometry: 1.0
species: 574171
type: SpeciesReference

482609
stoichiometry: 1.0
species: 574911
type: SpeciesReference

482946
stoichiometry: 1.0
species: 575011
type: SpeciesReference

480974
local parameters: 274499
local parameters: 274498
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

481083
stoichiometry: 1.0
species: 574191
type: SpeciesReference

274580
units: 479672
value: 7.5420478917E-13
type: LocalParameter

479806
stoichiometry: 1.0
species: 573871
type: SpeciesReference

274617
units: 479585
value: 3.0168E-12
type: LocalParameter

482874
stoichiometry: 1.0
species: 574451
type: SpeciesReference

575231
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 573851
type: Species

274627
units: 479585
value: 7.542E-13
type: LocalParameter

483188
stoichiometry: 1.0
species: 575111
type: SpeciesReference

274513
units: 479585
value: 7.542E-12
type: LocalParameter

481168
local parameters: 274507
local parameters: 274505
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

574491
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 573851
type: Species

575971
kinetic law: 481071
product: 481059
reactant: 481046
reactant: 481034
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

576491
kinetic law: 482331
product: 482319
reactant: 482307
reactant: 482295
notes: Kinetics same as GEF-bg_act-ras
fast: false
reversible: true
type: Reaction

274503
units: 479585
value: 1.387728E-12
type: LocalParameter

574631
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 573851
type: Species

480633
stoichiometry: 1.0
species: 574791
type: SpeciesReference

479745
stoichiometry: 1.0
species: 574071
type: SpeciesReference

574191
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 573851
type: Species

482970
stoichiometry: 1.0
species: 574951
type: SpeciesReference

480074
local parameters: 274457
local parameters: 274456
notes: kf*AA*PKC_slash_PKC_minus_cytosolic-kb*PKC_slash_PKC_minus_AA_star_
type: KineticLaw

482006
stoichiometry: 1.0
species: 574751
type: SpeciesReference

480330
stoichiometry: 1.0
species: 575291
type: SpeciesReference

481034
stoichiometry: 1.0
species: 575251
type: SpeciesReference

575431
kinetic law: 479866
product: 479854
reactant: 479842
fast: false
reversible: true
type: Reaction

575991
kinetic law: 481120
product: 481108
product: 481096
reactant: 481083
fast: false
reversible: false
type: Reaction

575331
constant: true
boundary condition: true
has only substance units: false
initial concentration: 0.08
initial amount: NaN
in compartment: 573851
type: Species

482367
stoichiometry: 1.0
species: 574831
type: SpeciesReference

274512
units: 479585
value: 3.0168E-11
type: LocalParameter

482682
stoichiometry: 1.0
species: 574111
type: SpeciesReference

482055
stoichiometry: 1.0
species: 574671
type: SpeciesReference

480391
stoichiometry: 1.0
species: 575251
type: SpeciesReference

481811
stoichiometry: 1.0
species: 574391
type: SpeciesReference

274572
units: 479585
value: 2.0112E-12
type: LocalParameter

482982
stoichiometry: 1.0
species: 575011
type: SpeciesReference

274582
units: 479585
value: 2.0112E-12
type: LocalParameter

483321
stoichiometry: 1.0
species: 574391
type: SpeciesReference

482295
stoichiometry: 1.0
species: 574751
type: SpeciesReference

574852
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.08
initial amount: NaN
in compartment: 573851
type: Species

575631
kinetic law: 480317
product: 480305
reactant: 480293
reactant: 480281
fast: false
reversible: true
type: Reaction

480269
local parameters: 274465
local parameters: 274464
notes: kf*temp_minus_PIP2*PLA2_slash_PLA2_minus_cytosolic-kb*PLA2_slash_PIP2_minus_PLA2_star_
type: KineticLaw

480986
stoichiometry: 1.0
species: 574151
type: SpeciesReference

482934
stoichiometry: 1.0
species: 574411
type: SpeciesReference

480620
stoichiometry: 1.0
species: 574771
type: SpeciesReference

481071
local parameters: 274502
local parameters: 274501
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

483068
stoichiometry: 1.0
species: 574371
type: SpeciesReference

573931
constant: false
boundary condition: false
has only substance units: false
initial concentration: 1.38955184301246E-17
initial amount: NaN
in compartment: 573851
type: Species

274592
units: 479585
value: 5.028E-12
type: LocalParameter

483273
stoichiometry: 1.0
species: 575071
type: SpeciesReference

574411
constant: false
boundary condition: false
has only substance units: false
initial concentration: 3.59997348183506
initial amount: NaN
in compartment: 573851
type: Species

481409
local parameters: 274518
notes: k3*PLA2_slash_PLA2_star__minus_Ca_slash_kenz_slash_kenz_cplx
type: KineticLaw

480062
stoichiometry: 1.0
species: 573991
type: SpeciesReference

574111
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.4
initial amount: NaN
in compartment: 573851
type: Species

574831
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 573851
type: Species

481022
local parameters: 274500
notes: k3*PLA2_slash_PLA2_minus_Ca_star__slash_kenz_slash_kenz_cplx
type: KineticLaw

482018
stoichiometry: 1.0
species: 574651
type: SpeciesReference

274583
units: 479585
value: 5.028E-13
type: LocalParameter

574311
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 573851
type: Species

274500
units: 479585
value: 6.7878E-13
type: LocalParameter

576351
kinetic law: 481993
product: 481980
product: 481968
reactant: 481956
fast: false
reversible: false
type: Reaction

576151
kinetic law: 481506
product: 481493
product: 481481
reactant: 481469
fast: false
reversible: false
type: Reaction

482694
stoichiometry: 1.0
species: 574951
type: SpeciesReference

574851
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 573851
type: Species

482355
stoichiometry: 1.0
species: 574731
type: SpeciesReference

274510
units: 479672
value: 1.88553567366E-12
type: LocalParameter

575031
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 573851
type: Species

274570
units: 479672
value: 3.77097654438E-14
type: LocalParameter

574391
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.5
initial amount: NaN
in compartment: 573851
type: Species

482283
local parameters: 274563
notes: k3*Ras_slash_GAP_slash_GAP_minus_inact_minus_ras_slash_GAP_minus_inact_minus_ras_cplx
type: KineticLaw

482994
stoichiometry: 1.0
species: 575051
type: SpeciesReference

481361
local parameters: 274517
local parameters: 274515
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

481823
stoichiometry: 1.0
species: 574591
type: SpeciesReference

483164
stoichiometry: 1.0
species: 574471
type: SpeciesReference

480998
stoichiometry: 1.0
species: 574091
type: SpeciesReference

482922
stoichiometry: 1.0
species: 575031
type: SpeciesReference

574511
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 573851
type: Species

483261
stoichiometry: 1.0
species: 574531
type: SpeciesReference

482898
stoichiometry: 1.0
species: 575031
type: SpeciesReference

274590
units: 479672
value: 2.45122481664E-13
type: LocalParameter

481689
stoichiometry: 1.0
species: 574551
type: SpeciesReference

480257
stoichiometry: 1.0
species: 574171
type: SpeciesReference

574451
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 573851
type: Species

274471
units: 479585
value: 5.028E-14
type: LocalParameter

482042
local parameters: 274552
local parameters: 274550
notes: k1*Ras_slash_GDP_minus_Ras*Ras_slash_inact_minus_GEF-k2*Ras_slash_inact_minus_GEF_slash_basal_GEF_activity_slash_basal_GEF_activity_cplx
type: KineticLaw

574591
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 573851
type: Species

274602
units: 479585
value: 2.0112E-12
type: LocalParameter

481604
local parameters: 274528
notes: k3*MAPK_slash_MAPKK_star__slash_MAPKKthr_slash_MAPKKthr_cplx
type: KineticLaw

481506
local parameters: 274523
notes: k3*MAPK_slash_MAPKK_star__slash_MAPKKtyr_slash_MAPKKtyr_cplx
type: KineticLaw

481289
stoichiometry: 1.0
species: 574091
type: SpeciesReference

480657
stoichiometry: 1.0
species: 574651
type: SpeciesReference

480209
stoichiometry: 1.0
species: 574131
type: SpeciesReference

574071
constant: false
boundary condition: false
has only substance units: false
initial concentration: 1.0
initial amount: NaN
in compartment: 573851
type: Species

483333
stoichiometry: 1.0
species: 575071
type: SpeciesReference

574552
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 573851
type: Species

482790
stoichiometry: 1.0
species: 574951
type: SpeciesReference

574571
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 573851
type: Species

274451
units: 479585
value: 1.257E-14
type: LocalParameter

482814
local parameters: 274592
local parameters: 274590
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

274603
units: 479585
value: 5.028E-13
type: LocalParameter

274560
units: 479672
value: 6.22030530222E-12
type: LocalParameter

274520
units: 479672
value: 4.07263949946E-12
type: LocalParameter

576631
kinetic law: 482670
product: 482658
product: 482646
reactant: 482633
fast: false
reversible: false
type: Reaction

481301
stoichiometry: 1.0
species: 574251
type: SpeciesReference

483430
stoichiometry: 1.0
species: 575071
type: SpeciesReference

274470
units: 479585
value: 5.028E-13
type: LocalParameter

479890
stoichiometry: 1.0
species: 573951
type: SpeciesReference

481968
stoichiometry: 1.0
species: 574471
type: SpeciesReference

576571
kinetic law: 482524
product: 482512
reactant: 482500
reactant: 482487
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

481519
stoichiometry: 1.0
species: 574451
type: SpeciesReference

481896
local parameters: 274543
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

482500
stoichiometry: 1.0
species: 575351
type: SpeciesReference

574531
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 573851
type: Species

576591
kinetic law: 482572
product: 482560
product: 482548
reactant: 482536
fast: false
reversible: false
type: Reaction

574551
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 573851
type: Species

274450
units: 479672
value: 1.50840957834E-16
type: LocalParameter

480743
local parameters: 274488
local parameters: 274487
notes: kf*CaM_slash_CaM*Ca^2-kb*CaM_slash_CaM_minus_TR2_minus_Ca2
type: KineticLaw

483237
stoichiometry: 1.0
species: 575071
type: SpeciesReference

480342
stoichiometry: 1.0
species: 574131
type: SpeciesReference

480669
stoichiometry: 1.0
species: 575231
type: SpeciesReference

480693
local parameters: 274486
local parameters: 274485
notes: kf*Ras_slash_inact_minus_GEF*CaM_slash_CaM_minus_Ca4-kb*Ras_slash_CaM_minus_GEF
type: KineticLaw

480890
local parameters: 274495
local parameters: 274494
notes: kf*MAPK_slash_craf_minus_1*Ras_slash_GTP_minus_Ras-kb*MAPK_slash_Raf_minus_GTP_minus_Ras
type: KineticLaw

573951
constant: false
boundary condition: false
has only substance units: false
initial concentration: 9.4351630867144E-21
initial amount: NaN
in compartment: 573851
type: Species

573911
constant: false
boundary condition: false
has only substance units: false
initial concentration: 1.75006629541236E-16
initial amount: NaN
in compartment: 573851
type: Species

480355
stoichiometry: 1.0
species: 574251
type: SpeciesReference

482826
stoichiometry: 1.0
species: 574991
type: SpeciesReference

575951
kinetic law: 481022
product: 481010
product: 480998
reactant: 480986
fast: false
reversible: false
type: Reaction

574931
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 573851
type: Species

574611
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 573851
type: Species

274605
units: 479672
value: 2.40856349364E-13
type: LocalParameter

575891
kinetic law: 480890
product: 480878
reactant: 480865
reactant: 480853
notes: 18 May 2003. This reaction is here to provide basal activity for MAPK as well as the potential for direct EGF stimulus without PKC activation. Based on model from FB/fb28c.g: the model used for MKP-1 turnover. The rates there were constrained by basal activity values.
fast: false
reversible: true
type: Reaction

575911
kinetic law: 480926
product: 480914
reactant: 480902
fast: false
reversible: true
type: Reaction

576851
kinetic law: 483200
product: 483188
reactant: 483176
reactant: 483164
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

480840
local parameters: 274493
local parameters: 274492
notes: kf*CaM_slash_CaM_minus_Ca3*Ca-kb*CaM_slash_CaM_minus_Ca4
type: KineticLaw

482512
stoichiometry: 1.0
species: 574891
type: SpeciesReference

575551
kinetic law: 480123
product: 480111
reactant: 480099
reactant: 480086
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

575851
kinetic law: 480791
product: 480779
reactant: 480767
reactant: 480755
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

481313
local parameters: 274513
notes: k3*PLA2_slash_DAG_minus_Ca_minus_PLA2_star__slash_kenz_slash_kenz_cplx
type: KineticLaw

480803
stoichiometry: 1.0
species: 575191
type: SpeciesReference

480755
stoichiometry: 1.0
species: 575211
type: SpeciesReference

575871
kinetic law: 480840
product: 480827
reactant: 480815
reactant: 480803
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

483225
stoichiometry: 1.0
species: 574531
type: SpeciesReference

576831
kinetic law: 483152
product: 483140
product: 483128
reactant: 483116
fast: false
reversible: false
type: Reaction

575571
kinetic law: 480172
product: 480160
reactant: 480147
reactant: 480135
notes: Reduced kf to 0.66X to match Shinomura et al data. Initial: kf = 3.3333e-9 New: 2e-9 Newer: 2e-8 kb was 0.2 now 2.
fast: false
reversible: true
type: Reaction

573991
constant: false
boundary condition: false
has only substance units: false
initial concentration: 1.81331211880138E-17
initial amount: NaN
in compartment: 573851
type: Species

482597
stoichiometry: 1.0
species: 575351
type: SpeciesReference

479939
stoichiometry: 1.0
species: 573911
type: SpeciesReference

MODEL9147091146
species: 574271
notes: This is a model of ERKII signaling which is bistable due to feedback. The feedback occurs through ERKII phosphorylation of phospholipase A2 (PLA2), leading to increased production of arachidonic acid (AA), which activates protein kinase C (PKC) which activates c-Raf which is upstream of ERKII.<br""> The model is a highly simplified variant of more detailed bistable models of MAPK signaling (Bhalla US, Iyengar R. Science. 1999 Jan 15;283(5400):381-7, Ajay SM, Bhalla US. Eur J Neurosci. 2004 Nov;20(10):2671-80) This model originates from BioModels Database: A Database of Annotated Published Models. It is copyright (c) 2005-2011 The BioModels.net Team. To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information. In summary, you are entitled to use this encoded model in absolutely any manner you deem suitable, verbatim, or with modification, alone or embedded it in a larger context, redistribute it, commercially or not, in a restricted way or not.. To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.
area units: area
species: 574531
reaction: 575831
species: 574411
reaction: 576471
species: 574371
species: 574491
species: 574691
reaction: 576591
reaction: 575811
reaction: 575651
reaction: 576651
units def: 479622
reaction: 576451
species: 574911
is described by: http://identifiers.org/pubmed/19404460
species: 575331
species: 575271
species: 574131
reaction: 575631
species: 574011
species: 574031
species: 574871
reaction: 576051
volume units: 679943
reaction: 575551
species: 574771
species: 574351
species: 574511
substance units: 479721
reaction: 576851
reaction: 576551
reaction: 575771
rule: 575371
species: 574991
compartment: 573851
species: 573911
reaction: 576571
units def: 479672
species: 574651
reaction: 575451
species: 573991
species: 574211
reaction: 576771
reaction: 575711
reaction: 576291
reaction: 576171
reaction: 576111
reaction: 576791
species: 574711
species: 575171
species: 575291
species: 575351
species: 574051
species: 574171
reaction: 576391
species: 574311
reaction: 576331
species: 574852
length unit: length
species: 574471
reaction: 576511
reaction: 575691
reaction: 575431
species: 574391
reaction: 576431
units def: 479585
reaction: 576251
species: 575051
reaction: 575411
species: 574971
species: 573951
reaction: 575571
reaction: 576731
species: 574851
reaction: 576231
species: 575111
reaction: 575591

482584
stoichiometry: 1.0
species: 574651
type: SpeciesReference

482706
stoichiometry: 1.0
species: 574971
type: SpeciesReference

274488
units: 479585
value: 9.0504E-12
type: LocalParameter

483285
stoichiometry: 1.0
species: 575131
type: SpeciesReference

574471
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 573851
type: Species

481640
stoichiometry: 1.0
species: 574552
type: SpeciesReference

483140
stoichiometry: 1.0
species: 575071
type: SpeciesReference

274475
units: 479585
value: 2.1369E-14
type: LocalParameter

274461
units: 479585
value: 2.514E-13
type: LocalParameter

576231
kinetic law: 481701
product: 481689
product: 481677
reactant: 481665
fast: false
reversible: false
type: Reaction

574731
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 573851
type: Species

483357
stoichiometry: 1.0
species: 574431
type: SpeciesReference

480367
local parameters: 274470
local parameters: 274469
notes: kf*DAG*PLA2_slash_PLA2_minus_Ca_star_-kb*PLA2_slash_DAG_minus_Ca_minus_PLA2_star_
type: KineticLaw

480160
stoichiometry: 1.0
species: 574051
type: SpeciesReference

482658
stoichiometry: 1.0
species: 575351
type: SpeciesReference

481469
stoichiometry: 1.0
species: 574491
type: SpeciesReference

574671
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 573851
type: Species

274607
units: 479585
value: 3.0168E-12
type: LocalParameter

481628
stoichiometry: 1.0
species: 574551
type: SpeciesReference

575151
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 573851
type: Species

575251
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: 573851
type: Species

575211
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 573851
type: Species

480111
stoichiometry: 1.0
species: 574031
type: SpeciesReference

576511
kinetic law: 482379
product: 482367
product: 482355
reactant: 482343
fast: false
reversible: false
type: Reaction

574711
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 573851
type: Species

482850
stoichiometry: 1.0
species: 574951
type: SpeciesReference

481848
local parameters: 274542
local parameters: 274540
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

480853
stoichiometry: 1.0
species: 574351
type: SpeciesReference

274489
units: 479672
value: 4.52522873502E-13
type: LocalParameter

274474
units: 479585
value: 1.257E-14
type: LocalParameter

274460
units: 479672
value: 2.26256696604E-15
type: LocalParameter

576431
kinetic law: 482187
product: 482175
product: 482163
reactant: 482151
fast: false
reversible: false
type: Reaction

574271
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 573851
type: Species

480767
stoichiometry: 1.0
species: 574852
type: SpeciesReference

576551
kinetic law: 482475
product: 482463
product: 482451
reactant: 482439
fast: false
reversible: false
type: Reaction

483213
stoichiometry: 1.0
species: 575111
type: SpeciesReference

274608
units: 479585
value: 7.542E-13
type: LocalParameter

576531
kinetic law: 482427
product: 482415
reactant: 482403
reactant: 482391
notes: Rate consts from Chen et al Biochem 32, 1032 (1993) k3 = k2 = 4 k1 = 9e-5 recalculated gives 1.666e-5, which is not very different. Looks like k3 is rate-limiting in this case: there is a huge amount of craf locked up in the enz complex. Let us assume a 10x higher Km, ie, lower affinity. k1 drops by 10x. Also changed k2 to 4x k3. Lowerd k1 to 1e-6 to balance 10X DAG sensitivity of PKC
fast: false
reversible: true
type: Reaction

480815
stoichiometry: 1.0
species: 574852
type: SpeciesReference

481653
local parameters: 274532
local parameters: 274530
notes: k1*MAPK_slash_MAPKK*MAPK_slash_Raf_minus_GTP_minus_Ras-k2*MAPK_slash_Raf_minus_GTP_minus_Ras_slash_Raf_minus_GTP_minus_Ras_dot_1_slash_Raf_minus_GTP_minus_Ras_dot_1_cplx
type: KineticLaw

576031
kinetic law: 481216
product: 481204
product: 481192
reactant: 481180
fast: false
reversible: false
type: Reaction

481457
local parameters: 274522
local parameters: 274520
notes: k1*MAPK_slash_MAPK*MAPK_slash_MAPKK_star_-k2*MAPK_slash_MAPKK_star__slash_MAPKKtyr_slash_MAPKKtyr_cplx
type: KineticLaw

482151
stoichiometry: 1.0
species: 574711
type: SpeciesReference

575291
constant: true
boundary condition: true
has only substance units: false
initial concentration: 12.1999469636701
initial amount: NaN
in compartment: 573851
type: Species

481944
local parameters: 274547
local parameters: 274545
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

480379
stoichiometry: 1.0
species: 574091
type: SpeciesReference

482802
stoichiometry: 1.0
species: 574991
type: SpeciesReference

482572
local parameters: 274578
notes: k3*PKC_minus_active_slash_PKC_minus_inact_minus_GAP_slash_PKC_minus_inact_minus_GAP_cplx
type: KineticLaw

482718
local parameters: 274587
local parameters: 274585
notes: k1*PLA2_slash_PLA2_minus_cytosolic*MAPK_star_-k2*MAPK_star__slash_MAPK_star__slash_MAPK_star__cplx
type: KineticLaw

274463
units: 479585
value: 1.257E-14
type: LocalParameter

483369
stoichiometry: 1.0
species: 575071
type: SpeciesReference

482910
local parameters: 274597
local parameters: 274595
notes: k1*MAPK_slash_MAPK_minus_tyr*MKP_minus_1-k2*MKP_minus_1_slash_MKP1_minus_tyr_minus_deph_slash_MKP1_minus_tyr_minus_deph_cplx
type: KineticLaw

274473
units: 479672
value: 7.5420478917E-13
type: LocalParameter

482862
local parameters: 274593
notes: k3*MAPK_star__slash_MAPK_star__minus_feedback_slash_MAPK_star__minus_feedback_cplx
type: KineticLaw

480123
local parameters: 274459
local parameters: 274458
notes: kf*PKC_slash_PKC_minus_cytosolic*DAG-kb*PKC_slash_PKC_minus_DAG
type: KineticLaw

481592
stoichiometry: 1.0
species: 574471
type: SpeciesReference

481616
stoichiometry: 1.0
species: 574391
type: SpeciesReference

274462
units: 479672
value: 1.25699218146E-13
type: LocalParameter

480779
stoichiometry: 1.0
species: 575191
type: SpeciesReference

482487
stoichiometry: 1.0
species: 574791
type: SpeciesReference

480950
stoichiometry: 1.0
species: 574131
type: SpeciesReference

480865
stoichiometry: 1.0
species: 574731
type: SpeciesReference

274472
units: 479585
value: 0.0
type: LocalParameter

482163
stoichiometry: 1.0
species: 574731
type: SpeciesReference

575351
constant: false
boundary condition: true
has only substance units: false
initial concentration: 0.3
initial amount: NaN
in compartment: 573851
type: Species

481956
stoichiometry: 1.0
species: 574631
type: SpeciesReference

480827
stoichiometry: 1.0
species: 575231
type: SpeciesReference

481750
local parameters: 274537
local parameters: 274535
notes: k1*MAPK_slash_MAPKK_minus_ser*MAPK_slash_Raf_minus_GTP_minus_Ras-k2*MAPK_slash_Raf_minus_GTP_minus_Ras_slash_Raf_minus_GTP_minus_Ras_dot_2_slash_Raf_minus_GTP_minus_Ras_dot_2_cplx
type: KineticLaw

481665
stoichiometry: 1.0
species: 574552
type: SpeciesReference

274459
units: 479585
value: 1.257E-14
type: LocalParameter

481762
stoichiometry: 1.0
species: 574571
type: SpeciesReference

480572
local parameters: 274480
local parameters: 274479
notes: kf*Ras_slash_GEF_star_-kb*Ras_slash_inact_minus_GEF
type: KineticLaw

274568
units: 479585
value: 1.257E-14
type: LocalParameter

481738
stoichiometry: 1.0
species: 574571
type: SpeciesReference

574991
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 573851
type: Species

482175
stoichiometry: 1.0
species: 574691
type: SpeciesReference

481433
stoichiometry: 1.0
species: 574471
type: SpeciesReference

481920
stoichiometry: 1.0
species: 574591
type: SpeciesReference

274445
units: 479585
value: 1.08539436E-12
type: LocalParameter

274465
units: 479585
value: 6.285E-14
type: LocalParameter

274484
units: 479585
value: 0.0
type: LocalParameter

479903
local parameters: 274449
local parameters: 274448
notes: kf*PKC_slash_PKC_minus_Ca_minus_DAG-kb*PKC_slash_PKC_minus_DAG_minus_memb_star_
type: KineticLaw

274498
units: 479672
value: 1.696972626E-13
type: LocalParameter

574011
constant: false
boundary condition: false
has only substance units: false
initial concentration: 8.46313975072925E-23
initial amount: NaN
in compartment: 573851
type: Species

479830
local parameters: 274445
local parameters: 274443
notes: kf*DAG*PKC_slash_PKC_minus_Ca-kb*PKC_slash_PKC_minus_Ca_minus_DAG
type: KineticLaw

576651
kinetic law: 482718
product: 482706
reactant: 482694
reactant: 482682
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

274479
units: 479585
value: 1.257E-13
type: LocalParameter

274540
units: 479672
value: 1.18513155294E-12
type: LocalParameter

482475
local parameters: 274573
notes: k3*PKC_minus_active_slash_PKC_minus_act_minus_raf_slash_PKC_minus_act_minus_raf_cplx
type: KineticLaw

574051
constant: false
boundary condition: false
has only substance units: false
initial concentration: 2.51882789710952E-19
initial amount: NaN
in compartment: 573851
type: Species

481531
stoichiometry: 1.0
species: 574471
type: SpeciesReference

479697
exponent: -1.0
scale: -6
multipler: 1.0
kind: MOLE
type: SBMLUnit

480523
stoichiometry: 1.0
species: 574591
type: SpeciesReference

274458
units: 479672
value: 7.5420478917E-17
type: LocalParameter

481580
stoichiometry: 1.0
species: 574951
type: SpeciesReference

481241
stoichiometry: 1.0
species: 574251
type: SpeciesReference

274567
units: 479585
value: 5.028E-14
type: LocalParameter

576611
kinetic law: 482621
product: 482609
reactant: 482597
reactant: 482584
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

482536
stoichiometry: 1.0
species: 574891
type: SpeciesReference

482633
stoichiometry: 1.0
species: 574911
type: SpeciesReference

480135
stoichiometry: 1.0
species: 574031
type: SpeciesReference

274553
units: 479585
value: 2.514E-15
type: LocalParameter

274464
units: 479672
value: 1.50840957834E-16
type: LocalParameter

480475
stoichiometry: 1.0
species: 574111
type: SpeciesReference

482319
stoichiometry: 1.0
species: 574851
type: SpeciesReference

482730
stoichiometry: 1.0
species: 574971
type: SpeciesReference

574091
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 573851
type: Species

274499
units: 479585
value: 2.71512E-12
type: LocalParameter

482127
stoichiometry: 1.0
species: 574711
type: SpeciesReference

274485
units: 479672
value: 2.51398436292E-11
type: LocalParameter

274478
units: 479585
value: 6.285E-14
type: LocalParameter

481349
stoichiometry: 1.0
species: 574311
type: SpeciesReference

575471
kinetic law: 479951
product: 479939
reactant: 479927
reactant: 479915
notes: Schaechter and Benowitz We have to increase Kf for conc scaling Changed kf to 2e-9 on Sept 19, 94. This gives better match.
fast: false
reversible: true
type: Reaction

481445
stoichiometry: 1.0
species: 574491
type: SpeciesReference

575731
kinetic law: 480535
product: 480523
reactant: 480511
reactant: 480499
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

481932
stoichiometry: 1.0
species: 574631
type: SpeciesReference

481397
stoichiometry: 1.0
species: 574291
type: SpeciesReference

576731
kinetic law: 482910
product: 482898
reactant: 482886
reactant: 482874
notes: The original kinetics have been modified to obey the k2 = 4 * k3 rule, while keeping kcat and Km fixed. As noted in the NOTES, the only constraining data point is the time course of MAPK dephosphorylation, which this model satisfies. It would be nice to have more accurate estimates of rate consts and MKP-1 levels from the literature. Effective Km : 67 nM kcat = 1.43 umol/min/mg
fast: false
reversible: true
type: Reaction

481860
stoichiometry: 1.0
species: 574611
type: SpeciesReference

481180
stoichiometry: 1.0
species: 574231
type: SpeciesReference

575491
kinetic law: 479988
product: 479975
reactant: 479963
notes: Assume slowish too. Schaechter and Benowitz
fast: false
reversible: true
type: Reaction

274457
units: 479585
value: 1.257E-14
type: LocalParameter

274447
units: 479585
value: 4.4027682E-13
type: LocalParameter

481774
stoichiometry: 1.0
species: 574471
type: SpeciesReference

481726
stoichiometry: 1.0
species: 574551
type: SpeciesReference

482187
local parameters: 274558
notes: k3*Ras_slash_GEF_star__slash_GEF_star__minus_act_minus_ras_slash_GEF_star__minus_act_minus_ras_cplx
type: KineticLaw

573971
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 573851
type: Species

482463
stoichiometry: 1.0
species: 575351
type: SpeciesReference

576711
kinetic law: 482862
product: 482850
product: 482838
reactant: 482826
fast: false
reversible: false
type: Reaction

274496
units: 479585
value: 2.514E-13
type: LocalParameter

481108
stoichiometry: 1.0
species: 574171
type: SpeciesReference

575751
kinetic law: 480572
product: 480559
reactant: 480547
fast: false
reversible: true
type: Reaction

274477
units: 479672
value: 1.25699218146E-12
type: LocalParameter

574951
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 573851
type: Species

274486
units: 479585
value: 1.257E-13
type: LocalParameter

575791
kinetic law: 480645
product: 480633
reactant: 480620
notes: Assume a reasonably good rate for dephosphorylating it, 1/sec
fast: false
reversible: true
type: Reaction

274456
units: 479672
value: 1.50840957834E-17
type: LocalParameter

274565
units: 479672
value: 1.24447819338E-13
type: LocalParameter

480147
stoichiometry: 1.0
species: 574091
type: SpeciesReference

274446
units: 479585
value: 1.5970185E-13
type: LocalParameter

574911
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 573851
type: Species

480535
local parameters: 274478
local parameters: 274477
notes: kf*MAPK_slash_craf_minus_1_star_*Ras_slash_GTP_minus_Ras-kb*MAPK_slash_Raf_star__minus_GTP_minus_Ras
type: KineticLaw

481253
stoichiometry: 1.0
species: 574271
type: SpeciesReference

479648
exponent: -2.0
scale: -6
multipler: 1.0
kind: MOLE
type: SBMLUnit

274555
units: 479672
value: 2.48886158382E-14
type: LocalParameter

575931
kinetic law: 480974
product: 480962
reactant: 480950
reactant: 480938
notes: 10 x raise oct22 12 x oct 24, set k2 = 4 * k3
fast: false
reversible: true
type: Reaction

274497
units: 479585
value: 2.514E-13
type: LocalParameter

482646
stoichiometry: 1.0
species: 574691
type: SpeciesReference

576791
kinetic law: 483055
product: 483042
product: 483030
reactant: 483018
fast: false
reversible: false
type: Reaction

483309
stoichiometry: 1.0
species: 575131
type: SpeciesReference

274466
units: 479672
value: 1.50840957834E-15
type: LocalParameter

480878
stoichiometry: 1.0
species: 574551
type: SpeciesReference

480487
local parameters: 274476
local parameters: 274475
notes: kf*PLA2_slash_PLA2_star_-kb*PLA2_slash_PLA2_minus_cytosolic
type: KineticLaw

274476
units: 479585
value: 0.0
type: LocalParameter

575771
kinetic law: 480608
product: 480596
reactant: 480584
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

576911
kinetic law: 483345
product: 483333
product: 483321
reactant: 483309
fast: false
reversible: false
type: Reaction

482115
stoichiometry: 1.0
species: 574691
type: SpeciesReference

482307
stoichiometry: 1.0
species: 574831
type: SpeciesReference

274487
units: 479622
value: 9.05051776470984E-12
type: LocalParameter

479609
exponent: -1.0
scale: 0
multipler: 1.0
kind: SECOND
type: SBMLUnit

480608
local parameters: 274482
local parameters: 274481
notes: kf*Ras_slash_GTP_minus_Ras-kb*Ras_slash_GDP_minus_Ras
type: KineticLaw

575271
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: 573851
type: Species

479782
local parameters: 274442
local parameters: 274441
notes: kf*PKC_slash_PKC_minus_cytosolic*Ca-kb*PKC_slash_PKC_minus_Ca
type: KineticLaw

574651
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.1
initial amount: NaN
in compartment: 573851
type: Species

274441
units: 479672
value: 7.5420478917E-14
type: LocalParameter

480293
stoichiometry: 1.0
species: 574131
type: SpeciesReference

479927
stoichiometry: 1.0
species: 574091
type: SpeciesReference

575171
constant: false
boundary condition: false
has only substance units: false
initial concentration: 20.0
initial amount: NaN
in compartment: 573851
type: Species

482451
stoichiometry: 1.0
species: 574371
type: SpeciesReference

274550
units: 479672
value: 1.24438339044E-15
type: LocalParameter

573871
constant: false
boundary condition: false
has only substance units: false
initial concentration: 3.72076372315036E-17
initial amount: NaN
in compartment: 573851
type: Species

274455
units: 479585
value: 6.285E-12
type: LocalParameter

575071
constant: false
boundary condition: false
has only substance units: false
initial concentration: 1.0
initial amount: NaN
in compartment: 573851
type: Species

576251
kinetic law: 481750
product: 481738
reactant: 481726
reactant: 481714
notes: Kinetics are the same as for the craf_1* activity, ie., k1=5.5e-6, k2=0.42, k3 = 0.105 These are basedo n Force et al PNAS USA 91 1270-1274, 1994., but k1 is scaled up 5x (ie., Km is scaled down 5x to the value used here and for craf_1* activity: Km = 0.1591).
fast: false
reversible: true
type: Reaction

576311
kinetic law: 481896
product: 481884
product: 481872
reactant: 481860
fast: false
reversible: false
type: Reaction

479597
exponent: 1.0
scale: 0
multipler: 1.0
kind: LITRE
type: SBMLUnit

481786
stoichiometry: 1.0
species: 574551
type: SpeciesReference

274494
units: 479672
value: 7.5420478917E-13
type: LocalParameter

480596
stoichiometry: 1.0
species: 574751
type: SpeciesReference

574251
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 573851
type: Species

481325
stoichiometry: 1.0
species: 575251
type: SpeciesReference

574151
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 573851
type: Species

482199
stoichiometry: 1.0
species: 574731
type: SpeciesReference

274480
units: 479585
value: 0.0
type: LocalParameter

481872
stoichiometry: 1.0
species: 574531
type: SpeciesReference

576931
kinetic law: 483394
product: 483382
reactant: 483369
reactant: 483357
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

274469
units: 479672
value: 3.77097654438E-16
type: LocalParameter

573851
constant: true
size: 1.257E-13
spatial dimensions: 3.0
type: Compartment

274530
units: 479672
value: 1.18513155294E-12
type: LocalParameter

576051
kinetic law: 481265
product: 481253
reactant: 481241
reactant: 481229
notes: 10 X raise oct 22 12 X raise oct 24 + conversion to k2 =4 * k3
fast: false
reversible: true
type: Reaction

482524
local parameters: 274577
local parameters: 274575
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

481385
stoichiometry: 1.0
species: 574091
type: SpeciesReference

574811
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 573851
type: Species

480499
stoichiometry: 1.0
species: 574371
type: SpeciesReference

575831
kinetic law: 480743
product: 480730
reactant: 480718
reactant: 480705
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

574351
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.5
initial amount: NaN
in compartment: 573851
type: Species

482103
stoichiometry: 1.0
species: 574751
type: SpeciesReference

575131
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 573851
type: Species

274563
units: 479585
value: 1.257E-12
type: LocalParameter

482838
stoichiometry: 1.0
species: 574431
type: SpeciesReference

274454
units: 479585
value: 1.257E-13
type: LocalParameter

576011
kinetic law: 481168
product: 481156
reactant: 481144
reactant: 481132
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

481265
local parameters: 274512
local parameters: 274510
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

274543
units: 479585
value: 3.771E-14
type: LocalParameter

480547
stoichiometry: 1.0
species: 574691
type: SpeciesReference

274495
units: 479585
value: 1.257E-13
type: LocalParameter

574691
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 573851
type: Species

576211
kinetic law: 481653
product: 481640
reactant: 481628
reactant: 481616
notes: Kinetics are the same as for the craf_1* activity, ie., k1=5.5e-6, k2=0.42, k3 = 0.105 These are basedo n Force et al PNAS USA 91 1270-1274, 1994., but k1 is scaled up 5x (ie., Km is scaled down 5x to the value used here and for craf_1* activity: Km = 0.1591).
fast: false
reversible: true
type: Reaction

576391
kinetic law: 482091
product: 482079
product: 482067
reactant: 482055
fast: false
reversible: false
type: Reaction

576111
kinetic law: 481409
product: 481397
product: 481385
reactant: 481373
fast: false
reversible: false
type: Reaction

479975
stoichiometry: 1.0
species: 573891
type: SpeciesReference

274481
units: 479585
value: 1.257E-17
type: LocalParameter

574291
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 573851
type: Species

274468
units: 479585
value: 1.257E-14
type: LocalParameter

480681
stoichiometry: 1.0
species: 574831
type: SpeciesReference

575811
kinetic law: 480693
product: 480681
reactant: 480669
reactant: 480657
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 28 Feb 2006: Increased affinity 36-fold to account for Ca input to MAPK cascade, possibly folding in other pathway inputs. 21 April 2006: Altered affinity to same level as pkm_mapk21.g model to prevent spontaneous turnon. Kf = 200, Kb = 1.
fast: false
reversible: true
type: Reaction

479685
exponent: 2.0
scale: 0
multipler: 1.0
kind: LITRE
type: SBMLUnit

575671
kinetic law: 480403
product: 480391
reactant: 480379
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

274552
units: 479585
value: 1.0056E-14
type: LocalParameter

573891
constant: false
boundary condition: false
has only substance units: false
initial concentration: 4.91368337311058E-18
initial amount: NaN
in compartment: 573851
type: Species

274443
units: 479672
value: 1.00557478458E-15
type: LocalParameter

576191
kinetic law: 481604
product: 481592
product: 481580
reactant: 481568
fast: false
reversible: false
type: Reaction

481799
local parameters: 274538
notes: k3*MAPK_slash_Raf_minus_GTP_minus_Ras_slash_Raf_minus_GTP_minus_Ras_dot_2_slash_Raf_minus_GTP_minus_Ras_dot_2_cplx
type: KineticLaw

576291
kinetic law: 481848
product: 481835
reactant: 481823
reactant: 481811
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

480281
stoichiometry: 1.0
species: 575271
type: SpeciesReference

479794
stoichiometry: 1.0
species: 575291
type: SpeciesReference

274453
units: 479585
value: 2.514E-14
type: LocalParameter

479915
stoichiometry: 1.0
species: 573871
type: SpeciesReference

574891
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 573851
type: Species

274562
units: 479585
value: 5.028E-12
type: LocalParameter

481884
stoichiometry: 1.0
species: 574591
type: SpeciesReference

481421
stoichiometry: 1.0
species: 574411
type: SpeciesReference

274542
units: 479585
value: 1.5084E-13
type: LocalParameter

274492
units: 479672
value: 5.8450752657E-14
type: LocalParameter

481373
stoichiometry: 1.0
species: 574311
type: SpeciesReference

574871
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 573851
type: Species

479635
exponent: 3.0
scale: 0
multipler: 1.0
kind: LITRE
type: SBMLUnit

274532
units: 479585
value: 1.5084E-13
type: LocalParameter

274482
units: 479585
value: 0.0
type: LocalParameter

274600
units: 479672
value: 1.88553567366E-11
type: LocalParameter

480584
stoichiometry: 1.0
species: 574731
type: SpeciesReference

479988
local parameters: 274453
local parameters: 274452
notes: kf*PKC_slash_PKC_minus_DAG_minus_AA-kb*PKC_slash_PKC_minus_DAG_minus_AA_star_
type: KineticLaw

480730
stoichiometry: 1.0
species: 575211
type: SpeciesReference

274442
units: 479585
value: 6.285E-14
type: LocalParameter

481337
stoichiometry: 1.0
species: 574291
type: SpeciesReference

274452
units: 479585
value: 2.514E-13
type: LocalParameter

274493
units: 479585
value: 1.257E-12
type: LocalParameter

481277
stoichiometry: 1.0
species: 574271
type: SpeciesReference

274483
units: 479585
value: 1.257E-14
type: LocalParameter

482030
stoichiometry: 1.0
species: 574671
type: SpeciesReference

480559
stoichiometry: 1.0
species: 574651
type: SpeciesReference

482621
local parameters: 274582
local parameters: 274580
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

482548
stoichiometry: 1.0
species: 574771
type: SpeciesReference