352916
units: 146944
value: 1.05E-13
type: LocalParameter

149145
stoichiometry: 1.0
species: 541731
type: SpeciesReference

352978
units: 146944
value: 1.104E-11
type: LocalParameter

149072
stoichiometry: 1.0
species: 541691
type: SpeciesReference

150839
stoichiometry: 1.0
species: 542871
type: SpeciesReference

148028
stoichiometry: 1.0
species: 541931
type: SpeciesReference

148223
stoichiometry: 1.0
species: 542331
type: SpeciesReference

352839
units: 146944
value: 0.0
type: LocalParameter

544971
kinetic law: 151505
product: 151493
product: 151481
reactant: 151469
fast: false
reversible: false
type: Reaction

352999
units: 146981
value: 9.996E-10
type: LocalParameter

541691
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 541094
type: Species

151397
stoichiometry: 1.0
species: 542611
type: SpeciesReference

150080
stoichiometry: 1.0
species: 541991
type: SpeciesReference

352964
units: 146981
value: 1.98E-12
type: LocalParameter

352906
units: 146944
value: 1.05E-13
type: LocalParameter

147220
stoichiometry: 1.0
species: 541211
type: SpeciesReference

542271
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 541094
type: Species

544951
kinetic law: 151457
product: 151445
reactant: 151433
reactant: 151421
notes: 22 Apr 2001: Based on MKP1 parms. The original kinetics have been modified to obey the k2 = 4 * k3 rule, while keeping kcat and Km fixed. The only constraining data point is the time course of MAPK dephosphorylation, which this model satisfies. The rates are treated as the same as for MKP-1, based on Chu et al 1995 JBC 271(11):6497-6501
fast: false
reversible: true
type: Reaction

151275
stoichiometry: 1.0
species: 542571
type: SpeciesReference

352898
units: 146944
value: 1.5E-13
type: LocalParameter

352936
units: 146981
value: 1.95E-13
type: LocalParameter

148976
stoichiometry: 1.0
species: 542931
type: SpeciesReference

148587
stoichiometry: 1.0
species: 542711
type: SpeciesReference

149898
stoichiometry: 1.0
species: 542031
type: SpeciesReference

352926
units: 146981
value: 3.9E-12
type: LocalParameter

352984
units: 146981
value: 1.5E-11
type: LocalParameter

150791
stoichiometry: 1.0
species: 542271
type: SpeciesReference

541671
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 541094
type: Species

150731
local parameters: 352973
notes: k3*PLA2_slash_PLA2_minus_Ca_star__slash_kenz_slash_kenz_cplx
type: KineticLaw

151445
stoichiometry: 1.0
species: 542751
type: SpeciesReference

149934
stoichiometry: 1.0
species: 542411
type: SpeciesReference

542072
constant: false
boundary condition: false
has only substance units: false
initial concentration: 4.0E-4
initial amount: NaN
in compartment: 541094
type: Species

149982
stoichiometry: 1.0
species: 541991
type: SpeciesReference

352958
units: 146944
value: 6.0E-12
type: LocalParameter

150213
stoichiometry: 1.0
species: 541991
type: SpeciesReference

542631
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 541094
type: Species

151056
stoichiometry: 1.0
species: 542391
type: SpeciesReference

543651
kinetic law: 148357
product: 148345
reactant: 148333
notes: This rate is based on the known ratio of GDP-Ras to GTP-Ras. Basal: Ras.GTP = 7% Stimulated 15% Time course is within 10 min, probably much faster as not all early data points are there. See Gibbs et al JBC 265(33):20437-20422
fast: false
reversible: true
type: Reaction

147979
stoichiometry: 1.0
species: 541911
type: SpeciesReference

352917
units: 146981
value: 3.3E-12
type: LocalParameter

150803
stoichiometry: 1.0
species: 541491
type: SpeciesReference

352692
units: 146944
value: 1.0E-16
type: LocalParameter

352979
units: 146981
value: 9.0E-12
type: LocalParameter

352998
units: 146944
value: 2.0E-14
type: LocalParameter

149739
stoichiometry: 1.0
species: 541691
type: SpeciesReference

352896
units: 146944
value: 6.0E-13
type: LocalParameter

150153
local parameters: 352940
notes: k3*MAPK_star__slash_MKP_minus_1_minus_phosph2_slash_MKP_minus_1_minus_phosph2_cplx
type: KineticLaw

352682
units: 146944
value: 2.0E-12
type: LocalParameter

149497
stoichiometry: 1.0
species: 541871
type: SpeciesReference

352907
units: 146944
value: 1.0E-12
type: LocalParameter

148890
local parameters: 352883
notes: k3*PKC_minus_active_slash_PKC_minus_inact_minus_GAP_slash_PKC_minus_inact_minus_GAP_cplx
type: KineticLaw

352628
units: 146981
value: 4.9998E-13
type: LocalParameter

352945
units: 146944
value: 1.0E-12
type: LocalParameter

147400
local parameters: 352658
local parameters: 352656
notes: kf*PKC_slash_PKC_minus_Ca_minus_DAG-kb*PKC_slash_PKC_minus_DAG_minus_memb_star_
type: KineticLaw

352983
units: 146944
value: 3.6E-11
type: LocalParameter

543631
kinetic law: 148321
product: 148309
reactant: 148296
notes: Dephosphorylation reaction to balance MAPK phosphorylation of PLA2. This is probably mediated by PP2A. Rates determined to keep the balance of phosphorylated and non-phosphorylated PLA2 reasonable. The constraining factor is the fold activation of PLA2 by MAPK.
fast: false
reversible: true
type: Reaction

352959
units: 146981
value: 1.98E-12
type: LocalParameter

147751
stoichiometry: 1.0
species: 541851
type: SpeciesReference

542611
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 541094
type: Species

542071
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 541094
type: Species

148235
local parameters: 352831
local parameters: 352829
notes: kf*DAG*PLA2_slash_PLA2_minus_Ca_star_-kb*PLA2_slash_DAG_minus_Ca_minus_PLA2_star_
type: KineticLaw

149340
stoichiometry: 1.0
species: 541811
type: SpeciesReference

150018
stoichiometry: 1.0
species: 542051
type: SpeciesReference

147232
local parameters: 352642
local parameters: 352640
notes: kf*Sos_slash_Grb2*Sos_slash_Sos-kb*Sos_slash_Sos_dot_Grb2
type: KineticLaw

150092
stoichiometry: 1.0
species: 542071
type: SpeciesReference

146956
exponent: 1.0
scale: 0
multipler: 1.0
kind: LITRE
type: SBMLUnit

352918
units: 146944
value: 4.2E-13
type: LocalParameter

352976
units: 146944
value: 4.416E-11
type: LocalParameter

542371
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 541094
type: Species

352904
units: 146981
value: 3.3E-12
type: LocalParameter

151385
stoichiometry: 1.0
species: 542691
type: SpeciesReference

149133
local parameters: 352896
local parameters: 352894
notes: k1*MAPK_slash_MAPK_minus_tyr*MAPK_slash_MAPKK_star_-k2*MAPK_slash_MAPKK_star__slash_MAPKKthr_slash_MAPKKthr_cplx
type: KineticLaw

150827
local parameters: 352978
notes: k3*PLA2_slash_PIP2_minus_PLA2_star__slash_kenz_slash_kenz_cplx
type: KineticLaw

352966
units: 146944
value: 2.5E-11
type: LocalParameter

149691
stoichiometry: 1.0
species: 541931
type: SpeciesReference

541516
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 541094
type: Species

544531
kinetic law: 150441
product: 150429
product: 150417
reactant: 150405
fast: false
reversible: false
type: Reaction

148575
stoichiometry: 1.0
species: 542611
type: SpeciesReference

149886
stoichiometry: 1.0
species: 541991
type: SpeciesReference

542691
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 541094
type: Species

149084
local parameters: 352893
notes: k3*MAPK_slash_MAPKK_star__slash_MAPKKtyr_slash_MAPKKtyr_cplx
type: KineticLaw

149946
stoichiometry: 1.0
species: 541991
type: SpeciesReference

150225
stoichiometry: 1.0
species: 541671
type: SpeciesReference

148939
local parameters: 352886
local parameters: 352884
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

149970
stoichiometry: 1.0
species: 542072
type: SpeciesReference

150647
stoichiometry: 1.0
species: 542871
type: SpeciesReference

151433
stoichiometry: 1.0
species: 542731
type: SpeciesReference

352956
units: 146944
value: 2.5E-11
type: LocalParameter

151287
stoichiometry: 1.0
species: 542511
type: SpeciesReference

544031
kinetic law: 149230
product: 149218
reactant: 149205
reactant: 149193
notes: Kinetics are the same as for the craf-1* activity, ie., k1=5.5e-6, k2=.42, k3 =0.105 These are based on Force et al PNAS USA 91 1270-1274 1994.
fast: false
reversible: true
type: Reaction

148988
local parameters: 352888
notes: k3*PKC_minus_active_slash_PKC_minus_act_minus_GEF_slash_PKC_minus_act_minus_GEF_cplx
type: KineticLaw

352938
units: 146944
value: 4.0E-12
type: LocalParameter

147196
stoichiometry: 1.0
species: 541191
type: SpeciesReference

149485
stoichiometry: 1.0
species: 542851
type: SpeciesReference

352694
units: 146944
value: 0.0
type: LocalParameter

352986
units: 146944
value: 2.4E-10
type: LocalParameter

150141
stoichiometry: 1.0
species: 541991
type: SpeciesReference

352919
units: 146944
value: 1.05E-13
type: LocalParameter

150695
stoichiometry: 1.0
species: 542231
type: SpeciesReference

543311
kinetic law: 147667
product: 147654
reactant: 147641
reactant: 147629
notes: This is one of the more interesting steps. Mechanistically it does not seem necessary at first glance. Turns out that one needs this step to quantitatively match the curves in Schaechter and Benowitz 1993 J Neurosci 13(10):4361 and Shinomura et al 1991 PNAS 88:5149-5153. There is a synergy between DAG and AA activation even at low Ca levels, which is most simply represented by this reaction. Tau is assumed to be fast. Kd comes from matching the experimental curves.
fast: false
reversible: true
type: Reaction

151068
local parameters: 352991
local parameters: 352989
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

150549
stoichiometry: 1.0
species: 541651
type: SpeciesReference

544431
kinetic law: 150201
modifier: 150189
product: 150177
reactant: 150165
notes: The original kinetics from Bhalla and Iyengar Science 1999 have now been modified to obey the k2 = 4 * k3 rule, while keeping kcat and Km fixed. The main constraining data point is the time course of MAPK dephosphorylation, which this model satisfies. See Charles et al 1993 PNAS 90:5292-5296 and Charles et al Oncogene 7:187-190 Effective Km : 67 nM kcat = 1.43 umol/min/mg
fast: false
reversible: false
type: Reaction

352905
units: 146944
value: 4.2E-13
type: LocalParameter

148503
stoichiometry: 1.0
species: 542911
type: SpeciesReference

352680
units: 146981
value: 1.8E-14
type: LocalParameter

352996
units: 146944
value: 8.0E-14
type: LocalParameter

542651
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 541094
type: Species

352894
units: 146981
value: 1.62E-11
type: LocalParameter

150815
stoichiometry: 1.0
species: 542251
type: SpeciesReference

544451
kinetic law: 150249
modifier: 150237
product: 150225
reactant: 150213
notes: See MKP1-tyr-deph
fast: false
reversible: false
type: Reaction

352947
units: 146908
value: 0.0666666666666667
type: LocalParameter

147763
stoichiometry: 1.0
species: 542831
type: SpeciesReference

542671
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.5
initial amount: NaN
in compartment: 541094
type: Species

542331
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 541094
type: Species

151529
stoichiometry: 1.0
species: 542731
type: SpeciesReference

147412
stoichiometry: 1.0
species: 541271
type: SpeciesReference

352925
units: 146944
value: 1.0E-11
type: LocalParameter

148926
stoichiometry: 1.0
species: 541551
type: SpeciesReference

147184
local parameters: 352638
local parameters: 352636
notes: kf*Sos_slash_Sos_star_-kb*Sos_slash_Sos
type: KineticLaw

352968
units: 146944
value: 6.0E-12
type: LocalParameter

542931
constant: false
boundary condition: true
has only substance units: false
initial concentration: 0.02
initial amount: NaN
in compartment: 541094
type: Species

151299
stoichiometry: 1.0
species: 542551
type: SpeciesReference

149715
local parameters: 352918
local parameters: 352917
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

543471
kinetic law: 147955
product: 147943
reactant: 147931
notes: This is a \'black box\' approximation to the process of translation. I assume that there is unity stoichiometry, that is, a single RNA gives a single protein. This is obviously wrong, but since the RNA level itself is just a ratio against baseline, the conversion factor is absorbed there.
fast: false
reversible: true
type: Reaction

352912
units: 146944
value: 6.4E-16
type: LocalParameter

543491
kinetic law: 147992
product: 147979
reactant: 147967
notes: This is just a basal rate of MKP-1 transcription scaled to give reasonable basal levels of the MKP-1.
fast: false
reversible: true
type: Reaction

148563
local parameters: 352863
local parameters: 352861
notes: kf*PDGFR_slash_SHC_star_-kb*PDGFR_slash_SHC
type: KineticLaw

352893
units: 146944
value: 1.5E-13
type: LocalParameter

542471
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 541094
type: Species

147107
stoichiometry: 1.0
species: 541231
type: SpeciesReference

151421
stoichiometry: 1.0
species: 541671
type: SpeciesReference

149108
stoichiometry: 1.0
species: 541691
type: SpeciesReference

542491
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 541094
type: Species

352954
units: 146981
value: 1.98E-12
type: LocalParameter

147244
stoichiometry: 1.0
species: 541471
type: SpeciesReference

352829
units: 146981
value: 3.0E-15
type: LocalParameter

149303
stoichiometry: 1.0
species: 541771
type: SpeciesReference

148817
stoichiometry: 1.0
species: 542931
type: SpeciesReference

147919
local parameters: 352805
local parameters: 352804
notes: kf*MAPK_star_^2-kb*MAPK_slash_nuc_MAPK_star_
type: KineticLaw

352815
units: 146981
value: 6.0E-11
type: LocalParameter

150006
local parameters: 352933
local parameters: 352931
notes: k1*MKP_minus_1*MAPK_star_-k2*MAPK_star__slash_MKP_minus_1_minus_phosph_slash_MKP_minus_1_minus_phosph_cplx
type: KineticLaw

352688
units: 146944
value: 3.7E-16
type: LocalParameter

542311
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 541094
type: Species

151481
stoichiometry: 1.0
species: 541631
type: SpeciesReference

149169
stoichiometry: 1.0
species: 541691
type: SpeciesReference

146968
exponent: -1.0
scale: 0
multipler: 1.0
kind: SECOND
type: SBMLUnit

543451
kinetic law: 147919
product: 147907
reactant: 147895
notes: A nuclear translocation step. This lumps in all sorts of processes into a single set of rates constrained by time courses. Furuno et al J Immunol 166:4416-4421 (2001): In within 6 min, out within 7. The outgoing path is dephosphorylated MAPK so this reac will be one-way. Kf=0.01, Kb=0.005. The reaction is 2nd order in MAPK*, to represent dimerization of transcription factors.
fast: false
reversible: true
type: Reaction

151373
stoichiometry: 1.0
species: 542631
type: SpeciesReference

352994
units: 146981
value: 1.98E-13
type: LocalParameter

352940
units: 146944
value: 1.0E-12
type: LocalParameter

543411
kinetic law: 147847
product: 147835
reactant: 147823
notes: 24 Apr 2K: Based on 12 Feb 2K: Scaled up 10x so kf=0.01, kb=0 13 Apr 2001: MKP1* Goes down too fast, equil amount too small. Note that tau for turnover is 150 min. Doesn\'t make sense to have this tau be so much less. Go for 1e-4
fast: false
reversible: true
type: Reaction

352969
units: 146981
value: 1.35E-12
type: LocalParameter

544331
kinetic law: 149958
product: 149946
product: 149934
reactant: 149922
fast: false
reversible: false
type: Reaction

147424
stoichiometry: 1.0
species: 541491
type: SpeciesReference

150622
stoichiometry: 1.0
species: 542091
type: SpeciesReference

151517
stoichiometry: 1.0
species: 541991
type: SpeciesReference

148914
stoichiometry: 1.0
species: 542931
type: SpeciesReference

352913
units: 146944
value: 1.6E-16
type: LocalParameter

542911
notes: Platelet-derived growth factor. Heterodimer Mol wt. is approx 30 KDa Deuel et al 1985 Cancer Surv. 4(4):633-53 Conc of 50 ng/ml is close to saturating, and is used by P. Ram (personal communication). Other refs use 65 ng/ml Weise RJ et al 1995 JBC 270(7):3442-3446 A stimulus of 5 min is commonly used. Conversion factor: 1ng/ml = (1e-9/30K)* 1000 Moles/litre = 3e-11M = 3e-5 uM So 50 ng/ml ~ 1.5 nM.
constant: true
boundary condition: true
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 541094
type: Species

352686
units: 146944
value: 0.0
type: LocalParameter

352696
units: 146944
value: 1.0E-16
type: LocalParameter

352903
units: 146944
value: 1.05E-13
type: LocalParameter

147775
local parameters: 352694
local parameters: 352692
notes: kf*MAPK_slash_MKP_minus_1_star__star_-kb*MAPK_slash_Ubiquitination
type: KineticLaw

541571
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.2
initial amount: NaN
in compartment: 541094
type: Species

352816
units: 146944
value: 5.0E-13
type: LocalParameter

147134
stoichiometry: 1.0
species: 541171
type: SpeciesReference

352800
units: 146944
value: 1.0E-16
type: LocalParameter

148210
stoichiometry: 1.0
species: 542211
type: SpeciesReference

149218
stoichiometry: 1.0
species: 541791
type: SpeciesReference

543431
kinetic law: 147883
product: 147871
reactant: 147859
notes: 24 Apr 2K, based on 12 Feb 2K: Scaled up 10x to kf=0.01, kb=0 13 Apr 2001. Slowing down to 0.0001 to match turnover rates.
fast: false
reversible: true
type: Reaction

352941
units: 146944
value: 1.0E-12
type: LocalParameter

352993
units: 146944
value: 1.2E-10
type: LocalParameter

150249
local parameters: 352947
local parameters: 352945
notes: kcat*MKP_minus_1*MAPK_star_/(Km+MAPK_star_)
type: KineticLaw

542511
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.2
initial amount: NaN
in compartment: 541094
type: Species

352914
units: 146981
value: 3.3E-12
type: LocalParameter

352881
units: 146944
value: 1.0E-10
type: LocalParameter

149994
stoichiometry: 1.0
species: 542051
type: SpeciesReference

147172
stoichiometry: 1.0
species: 541251
type: SpeciesReference

352951
units: 146944
value: 2.5E-11
type: LocalParameter

352891
units: 146944
value: 6.0E-13
type: LocalParameter

148551
stoichiometry: 1.0
species: 542671
type: SpeciesReference

147448
local parameters: 352662
local parameters: 352660
notes: kf*PKC_slash_PKC_minus_Ca*AA-kb*PKC_slash_PKC_minus_Ca_minus_AA_star_
type: KineticLaw

148964
stoichiometry: 1.0
species: 542451
type: SpeciesReference

544571
kinetic law: 150537
product: 150525
product: 150513
reactant: 150501
fast: false
reversible: false
type: Reaction

544591
kinetic law: 150585
product: 150573
reactant: 150561
reactant: 150549
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 assumed to be PP2A.
fast: false
reversible: true
type: Reaction

541891
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 541111
type: Species

151361
local parameters: 353006
local parameters: 353004
notes: k1*PDGFR_slash_SHC*PDGFR_slash_L_dot_PDGFR-k2*PDGFR_slash_L_dot_PDGFR_slash_phosph_Shc_slash_phosph_Shc_cplx
type: KineticLaw

543111
kinetic law: 147232
product: 147220
reactant: 147208
reactant: 147196
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. Porfiri and McCormick JBC 271 also have related data. After comparing with the time-course of 1 min and the efficacy of activation of Ras, settle on Kd of 0.672 which is close to the Chook et al value.
fast: false
reversible: true
type: Reaction

149205
stoichiometry: 1.0
species: 541771
type: SpeciesReference

352928
units: 146944
value: 8.0E-11
type: LocalParameter

149157
stoichiometry: 1.0
species: 541991
type: SpeciesReference

148829
stoichiometry: 1.0
species: 541531
type: SpeciesReference

147256
stoichiometry: 1.0
species: 542811
type: SpeciesReference

147147
local parameters: 352634
local parameters: 352632
notes: kf*Sos_slash_Sos_star_*Sos_slash_Grb2-kb*Sos_slash_Sos_star__dot_Grb2
type: KineticLaw

149060
stoichiometry: 1.0
species: 541671
type: SpeciesReference

148296
stoichiometry: 1.0
species: 542411
type: SpeciesReference

147340
stoichiometry: 1.0
species: 541271
type: SpeciesReference

352827
units: 146944
value: 1.0E-13
type: LocalParameter

147907
stoichiometry: 1.0
species: 541871
type: SpeciesReference

352915
units: 146944
value: 4.2E-13
type: LocalParameter

352684
units: 146944
value: 4.0E-13
type: LocalParameter

147787
stoichiometry: 1.0
species: 541831
type: SpeciesReference

151505
local parameters: 353013
notes: k3*MKP_minus_2_slash_MKP2_minus_tyr_minus_deph_slash_MKP2_minus_tyr_minus_deph_cplx
type: KineticLaw

146994
exponent: 2.0
scale: 0
multipler: 1.0
kind: LITRE
type: SBMLUnit

541611
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.18
initial amount: NaN
in compartment: 541094
type: Species

541131
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 541094
type: Species

147436
stoichiometry: 1.0
species: 541311
type: SpeciesReference

148902
stoichiometry: 1.0
species: 542431
type: SpeciesReference

150610
stoichiometry: 1.0
species: 541591
type: SpeciesReference

352698
units: 146944
value: 0.0
type: LocalParameter

352901
units: 146944
value: 4.2E-13
type: LocalParameter

149727
stoichiometry: 1.0
species: 541971
type: SpeciesReference

543591
kinetic law: 148235
product: 148223
reactant: 148210
reactant: 148197
notes: Synergistic activation of PLA2 by Ca and DAG. Based on Leslie and Channon 1990 BBA 1045:261 The Kd is rather large and may reflect the complications in measuring DAG. For this model it is not critical since DAG is held fixed.
fast: false
reversible: true
type: Reaction

541151
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 541094
type: Species

543191
kinetic law: 147400
product: 147388
reactant: 147376
notes: membrane translocation step for Ca.DAG.PKC complex. Rates constrained from Shinomura et al 1991 PNAS 88:5149-5153 and Schaechter and Benowitz 1993 J Neurosci 13(10):4361 as derived in the references cited in PKC general notes.
fast: false
reversible: true
type: Reaction

544231
kinetic law: 149715
product: 149703
reactant: 149691
reactant: 149679
notes: Same kinetics as other c-raf activated forms. See Force et al PNAS 91 1270-1274 1994.
fast: false
reversible: true
type: Reaction

543851
kinetic law: 148793
product: 148781
product: 148769
reactant: 148757
fast: false
reversible: false
type: Reaction

149958
local parameters: 352930
notes: k3*MAPK_star__slash_MAPK_star__slash_MAPK_star__cplx
type: KineticLaw

150525
stoichiometry: 1.0
species: 542091
type: SpeciesReference

541531
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 541094
type: Species

352981
units: 146944
value: 1.44E-10
type: LocalParameter

352953
units: 146944
value: 6.0E-12
type: LocalParameter

151238
stoichiometry: 1.0
species: 542551
type: SpeciesReference

352802
units: 146944
value: 0.0
type: LocalParameter

352899
units: 146981
value: 3.3E-12
type: LocalParameter

352943
units: 146908
value: 0.0666666666666667
type: LocalParameter

543791
kinetic law: 148647
product: 148635
reactant: 148623
reactant: 148611
notes: Rates from Orita et al JBC 268(34):25542-25546
fast: false
reversible: true
type: Reaction

352991
units: 146944
value: 4.8E-10
type: LocalParameter

352818
units: 146981
value: 1.00002E-12
type: LocalParameter

149667
local parameters: 352916
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

541271
constant: false
boundary condition: false
has only substance units: false
initial concentration: 3.72083333333333E-17
initial amount: NaN
in compartment: 541094
type: Species

147055
stoichiometry: 1.0
species: 541211
type: SpeciesReference

150417
stoichiometry: 1.0
species: 541751
type: SpeciesReference

146932
exponent: 1.0
scale: -6
multipler: 1.0
kind: MOLE
type: SBMLUnit

542051
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 541094
type: Species

151590
stoichiometry: 1.0
species: 542731
type: SpeciesReference

542751
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 541094
type: Species

149012
stoichiometry: 1.0
species: 541691
type: SpeciesReference

543771
kinetic law: 148599
product: 148587
reactant: 148575
notes: Original model derived from EGFR model. 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 26 apr 2001: Keq too low for the PDGF model. Now Kf=0.001,Kb=0.00066 The previously calculated internalization equilibrium led to very high internalization which shifted the effective dependence of the receptor on PDGF so it looked like the receptor binding was higher affinity than experimentally determined. Used two constraining factors: 1. Time course of SHC phosphorylation/dephosphorylation which is fast on, but 10-20 minutes off. 2. Conc dependence of MAPK on PDGF has a halfmax around 3ng/ml. See Brondello et al 1997 JBC 272(2):1368-1376 and Brondello et al 1999 Science 286:2514-1517.
fast: false
reversible: true
type: Reaction

541451
constant: false
boundary condition: false
has only substance units: false
initial concentration: 2.51883333333333E-19
initial amount: NaN
in compartment: 541094
type: Species

148623
stoichiometry: 1.0
species: 541131
type: SpeciesReference

147006
exponent: -1.0
scale: -6
multipler: 1.0
kind: MOLE
type: SBMLUnit

147739
local parameters: 352690
local parameters: 352688
notes: kf*MKP_minus_1-kb*MAPK_slash_Ubiquitination
type: KineticLaw

352662
units: 146944
value: 1.0E-13
type: LocalParameter

147883
local parameters: 352802
local parameters: 352800
notes: kf*MAPK_slash_MKP_minus_1_star__star_-kb*MAPK_slash_MKP_minus_1_minus_ser359_star_
type: KineticLaw

542731
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.002
initial amount: NaN
in compartment: 541094
type: Species

541471
constant: false
boundary condition: false
has only substance units: false
initial concentration: 1.0
initial amount: NaN
in compartment: 541094
type: Species

147799
stoichiometry: 1.0
species: 542831
type: SpeciesReference

543751
kinetic law: 148563
product: 148551
reactant: 148539
notes: Time course of decline of phosph is 20 min from Sasaoka et al 1994 JBC 269(51):32621. Part of this is the turnoff time of the EGFR itself. Lets assume a tau of 10 min for this dephosphorylation as a first pass. 27 Apr 2001: Dephosph too slow, shifts SHC balance over to phosphorylated form. Increase Kf to 0.01. This gives a reasonable overall time-course.
fast: false
reversible: true
type: Reaction

148309
stoichiometry: 1.0
species: 542191
type: SpeciesReference

542011
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 541094
type: Species

544091
kinetic law: 149377
product: 149365
product: 149352
reactant: 149340
fast: false
reversible: false
type: Reaction

352672
units: 146981
value: 1.2E-16
type: LocalParameter

149606
stoichiometry: 1.0
species: 541951
type: SpeciesReference

148357
local parameters: 352843
local parameters: 352841
notes: kf*Ras_slash_GEF_star_-kb*Ras_slash_inact_minus_GEF
type: KineticLaw

543231
kinetic law: 147484
product: 147472
reactant: 147460
notes: Membrane translocation step for PKC-DAG-AA complex. Rates from matching concentration-effect data in our two main references: Schaechter and Benowitz 1993 J Neurosci 13(10):4361 and Shinomura et al 1988 PNAS 88: 5149-5153
fast: false
reversible: true
type: Reaction

147352
stoichiometry: 1.0
species: 541331
type: SpeciesReference

147823
stoichiometry: 1.0
species: 541831
type: SpeciesReference

147691
stoichiometry: 1.0
species: 542871
type: SpeciesReference

542091
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.224
initial amount: NaN
in compartment: 541094
type: Species

542811
notes: This calcium pool is treated as being buffered to a steady 0.08 uM, which is the resting level.
constant: true
boundary condition: true
has only substance units: false
initial concentration: 0.08
initial amount: NaN
in compartment: 541094
type: Species

148707
stoichiometry: 1.0
species: 541571
type: SpeciesReference

541491
constant: false
boundary condition: false
has only substance units: false
initial concentration: 6.12
initial amount: NaN
in compartment: 541094
type: Species

542711
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 541094
type: Species

541791
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 541094
type: Species

147160
stoichiometry: 1.0
species: 541231
type: SpeciesReference

149850
stoichiometry: 1.0
species: 541991
type: SpeciesReference

151565
stoichiometry: 1.0
species: 542771
type: SpeciesReference

150779
local parameters: 352976
local parameters: 352974
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

147931
stoichiometry: 1.0
species: 541911
type: SpeciesReference

149000
stoichiometry: 1.0
species: 541631
type: SpeciesReference

541431
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 541094
type: Species

149328
local parameters: 352905
local parameters: 352904
notes: k1*MAPK_slash_MAPKK_minus_ser*MAPK_slash_RGR-k2*MAPK_slash_RGR_slash_RGR_dot_2_slash_RGR_dot_2_cplx
type: KineticLaw

148635
stoichiometry: 1.0
species: 541151
type: SpeciesReference

544511
kinetic law: 150393
product: 150381
reactant: 150369
reactant: 150357
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

MODEL9070467164
reaction: 544871
species: 541971
species: 542511
species: 542711
species: 542811
species: 541191
reaction: 543971
reaction: 544191
species: 541331
species: 542271
species: 541411
reaction: 543091
area units: area
reaction: 544491
species: 542851
reaction: 543151
reaction: 544651
units def: 146908
reaction: 543471
species: 542531
species: 542251
reaction: 543951
reaction: 543811
reaction: 544971
species: 541151
species: 541831
is described by: http://identifiers.org/pubmed/12169734
species: 541351
compartment: 541094
species: 541431
reaction: 543991
species: 542051
length unit: length
reaction: 544211
species: 542691
reaction: 543331
species: 542171
species: 542011
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reaction: 544891
species: 542031
reaction: 543651
reaction: 543731
species: 541931
reaction: 544171
reaction: 544251
reaction: 544411
species: 541531
species: 541516
reaction: 544631
reaction: 543171
reaction: 544451
reaction: 543111
reaction: 543511
species: 541731
reaction: 543571
species: 542211
reaction: 543831
reaction: 543911
reaction: 544931
species: 541171
compartment: 541111
species: 541311
type: SBMLModel
reaction: 543311
species: 541771
species: 542151
reaction: 544231
species: 542651
species: 542231
reaction: 544991
reaction: 543491
reaction: 543351
species: 541131
reaction: 543751
reaction: 543611
units def: 146981
reaction: 544271
reaction: 544131
species: 541791

542771
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 541094
type: Species

146920
exponent: -1.0
scale: 0
multipler: 1.0
kind: LITRE
type: SBMLUnit

150429
stoichiometry: 1.0
species: 542091
type: SpeciesReference

149679
stoichiometry: 1.0
species: 541751
type: SpeciesReference

147292
stoichiometry: 1.0
species: 542791
type: SpeciesReference

544051
kinetic law: 149278
product: 149266
product: 149254
reactant: 149242
fast: false
reversible: false
type: Reaction

352660
units: 146981
value: 1.2E-15
type: LocalParameter

148442
stoichiometry: 1.0
species: 541571
type: SpeciesReference

147018
exponent: -1.0
scale: 0
multipler: 1.0
kind: SECOND
type: SBMLUnit

147727
stoichiometry: 1.0
species: 542831
type: SpeciesReference

147895
stoichiometry: 2.0
species: 541991
type: SpeciesReference

352674
units: 146944
value: 1.0E-13
type: LocalParameter

151409
local parameters: 353008
notes: k3*PDGFR_slash_L_dot_PDGFR_slash_phosph_Shc_slash_phosph_Shc_cplx
type: KineticLaw

541411
constant: false
boundary condition: false
has only substance units: false
initial concentration: 8.46316666666667E-23
initial amount: NaN
in compartment: 541094
type: Species

542791
notes: Baseline in model is 11.661 uM. DAG is pretty nasty to estimate. In this model we just hold it fixed at this baseline level. Data sources are many and varied and sometimes difficult to reconcile. Welsh and Cabot 1987 JCB 35:231-245: DAG degradation Bocckino et al JBC 260(26):14201-14207: hepatocytes stim with vasopressin: 190 uM. Bocckino et al 1987 JBC 262(31):15309-15315: DAG rises from 70 to 200 ng/mg wet weight, approx 150 to 450 uM. Prescott and Majerus 1983 JBC 258:764-769: Platelets: 6 uM. Also see Rittenhouse-Simmons 1979 J Clin Invest 63. Sano et al JBC 258(3):2010-2013: Report a nearly 10 fold rise. Habenicht et al 1981 JBC 256(23)12329-12335: 3T3 cells with PDGF stim: 27 uM Cornell and Vance 1987 BBA 919:23-36: 10x rise from 10 to 100 uM. Summary: I see much lower rises in my PLC models, but the baseline could be anywhere from 5 to 100 uM. I have chosen about 11 uM based on the stimulus -response characteristics from the Schaechter and Benowitz paper and the Shinomura et al papers.
constant: true
boundary condition: true
has only substance units: false
initial concentration: 11.661
initial amount: NaN
in compartment: 541094
type: Species

544011
kinetic law: 149181
product: 149169
product: 149157
reactant: 149145
fast: false
reversible: false
type: Reaction

544191
kinetic law: 149618
product: 149606
reactant: 149594
reactant: 149582
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. They report Km for MAPKK of 0.8 uM. and a Vmax of ~500 fm/min/ug. These parms cannot reach the observed 4X stimulation of MAPK. So we increase the affinity, ie, raise k1 5x to 5.5e-6 which is equivalent to 5-fold reduction in Km to about 0.16. This is, of course, dependent on the amount of MAPKK present.
fast: false
reversible: true
type: Reaction

148369
stoichiometry: 1.0
species: 542491
type: SpeciesReference

149618
local parameters: 352915
local parameters: 352914
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

149315
stoichiometry: 1.0
species: 541811
type: SpeciesReference

543331
kinetic law: 147703
product: 147691
reactant: 147679
notes: Degradation pathway for AA. APC is a convenient buffered pool to dump it back into, though the actual metabolism is probably far more complex. For the purposes of the full model we use a rate of degradation of 0.4/sec to give a dynamic range of AA comparable to what is seen experimentally. Wijkander and Sundler 1991 Eur J Biochem 202:873 Leslie and Channon 1990 BBA 1045:261
fast: false
reversible: true
type: Reaction

544711
kinetic law: 150876
product: 150864
reactant: 150852
reactant: 150839
notes: Based on AA generation by different stimuli according to Leslie and Channon 1990 BBA 1045:261
fast: false
reversible: true
type: Reaction

147364
local parameters: 352654
local parameters: 352652
notes: kf*PKC_slash_PKC_minus_Ca-kb*PKC_slash_PKC_minus_Ca_minus_memb_star_
type: KineticLaw

147811
local parameters: 352698
local parameters: 352696
notes: kf*MAPK_slash_MKP_minus_1_minus_ser359_star_-kb*MAPK_slash_Ubiquitination
type: KineticLaw

150767
stoichiometry: 1.0
species: 542271
type: SpeciesReference

542411
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 541094
type: Species

151577
stoichiometry: 1.0
species: 541671
type: SpeciesReference

542151
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 541094
type: Species

147094
local parameters: 352630
local parameters: 352628
notes: kf*Sos_slash_Sos_dot_Grb2*PDGFR_slash_SHC_star_-kb*Shc_star__dot_Sos_dot_Grb2
type: KineticLaw

149291
stoichiometry: 1.0
species: 541751
type: SpeciesReference

147943
stoichiometry: 1.0
species: 542072
type: SpeciesReference

541111
constant: true
size: 2.0E-13
spatial dimensions: 3.0
type: Compartment

542351
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 541094
type: Species

148951
stoichiometry: 1.0
species: 541551
type: SpeciesReference

147715
stoichiometry: 1.0
species: 542072
type: SpeciesReference

151250
stoichiometry: 1.0
species: 542571
type: SpeciesReference

147304
stoichiometry: 1.0
species: 541271
type: SpeciesReference

352973
units: 146944
value: 5.4E-12
type: LocalParameter

544611
kinetic law: 150635
product: 150622
product: 150610
reactant: 150598
fast: false
reversible: false
type: Reaction

148647
local parameters: 352871
local parameters: 352869
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

147280
local parameters: 352646
local parameters: 352644
notes: kf*PKC_slash_PKC_minus_cytosolic*Ca-kb*PKC_slash_PKC_minus_Ca
type: KineticLaw

148430
local parameters: 352851
local parameters: 352849
notes: kf*Ras_slash_GAP_star_-kb*Ras_slash_GAP
type: KineticLaw

544111
kinetic law: 149425
modifier: 149413
product: 149401
reactant: 149389
notes: 3 Feb 2000. Same rates as MKP-1.
fast: false
reversible: false
type: Reaction

544311
kinetic law: 149910
product: 149898
reactant: 149886
reactant: 149874
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. Numbers are from Sanghera et al JBC 265 pp 52 , 1990. From Nemenoff et al 1993 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 total protein in fig 5 I take the Vmax to be higher for PLA2 given the fold activation of PLA2 by MAPK. This is actually a balance term between MAPK and the dephosphorylation step.
fast: false
reversible: true
type: Reaction

544631
kinetic law: 150683
product: 150671
reactant: 150659
reactant: 150647
notes: Based on Leslie and Channon 1990 BBA 1045:261, in relation to the other PLA2 inputs (not including MAPK). Ca alone is rather a weak input.
fast: false
reversible: true
type: Reaction

149036
local parameters: 352891
local parameters: 352889
notes: k1*MAPK_slash_MAPK*MAPK_slash_MAPKK_star_-k2*MAPK_slash_MAPKK_star__slash_MAPKKtyr_slash_MAPKKtyr_cplx
type: KineticLaw

352974
units: 146981
value: 2.76E-12
type: LocalParameter

352989
units: 146981
value: 3.0E-11
type: LocalParameter

149181
local parameters: 352898
notes: k3*MAPK_slash_MAPKK_star__slash_MAPKKthr_slash_MAPKKthr_cplx
type: KineticLaw

147042
exponent: 1.0
scale: -6
multipler: 1.0
kind: MOLE
type: SBMLUnit

150683
local parameters: 352971
local parameters: 352969
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

544851
kinetic law: 151214
product: 151202
product: 151189
reactant: 151177
fast: false
reversible: false
type: Reaction

544391
kinetic law: 150104
product: 150092
reactant: 150080
reactant: 150068
notes: 3 Feb 2000. See Brondello et al Science 286:2514 1999. Rates assumed standard MAPK rates based on Sanghera et al JBC 265(1):53-57 1990. The Vmax is scaled down by 10 fold to match the time-courses from the Brondello experiment.
fast: false
reversible: true
type: Reaction

541591
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 541094
type: Species

544671
kinetic law: 150779
product: 150767
reactant: 150755
reactant: 150743
notes: Based on Leslie and Channon 1990 BBA 1045:261.
fast: false
reversible: true
type: Reaction

149874
stoichiometry: 1.0
species: 542191
type: SpeciesReference

544691
kinetic law: 150827
product: 150815
product: 150803
reactant: 150791
fast: false
reversible: false
type: Reaction

149096
stoichiometry: 1.0
species: 541671
type: SpeciesReference

150755
stoichiometry: 1.0
species: 542251
type: SpeciesReference

151469
stoichiometry: 1.0
species: 542751
type: SpeciesReference

149910
local parameters: 352928
local parameters: 352926
notes: k1*PLA2_slash_PLA2_minus_cytosolic*MAPK_star_-k2*MAPK_star__slash_MAPK_star__slash_MAPK_star__cplx
type: KineticLaw

147955
local parameters: 352810
local parameters: 352809
notes: kf*MAPK_slash_MKP1_minus_RNA-kb*MKP_minus_1
type: KineticLaw

149121
stoichiometry: 1.0
species: 541731
type: SpeciesReference

148333
stoichiometry: 1.0
species: 542451
type: SpeciesReference

544651
kinetic law: 150731
product: 150719
product: 150707
reactant: 150695
fast: false
reversible: false
type: Reaction

147376
stoichiometry: 1.0
species: 541411
type: SpeciesReference

150321
stoichiometry: 1.0
species: 541571
type: SpeciesReference

148247
stoichiometry: 1.0
species: 542411
type: SpeciesReference

147605
stoichiometry: 1.0
species: 541431
type: SpeciesReference

352797
units: 146944
value: 0.0
type: LocalParameter

352988
units: 146944
value: 6.0E-11
type: LocalParameter

541311
constant: false
boundary condition: false
has only substance units: false
initial concentration: 1.75E-16
initial amount: NaN
in compartment: 541094
type: Species

352971
units: 146944
value: 2.16E-11
type: LocalParameter

541731
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 541094
type: Species

148659
stoichiometry: 1.0
species: 541151
type: SpeciesReference

542891
notes: This is a steady PIP2 input to PLA2. The sensitivity of PLA2 to PIP2 discussed below does not match with the reported free levels which are used by the phosphlipase Cs. My understanding is that there may be different pools of PIP2 available for stimulating PLA2 as opposed to being substrates for PLCs. For that reason I have given this PIP2 pool a separate identity. As it is a steady input this is not a problem in this model. Majerus et al Cell 37:701-703 report a brain concentration of 0.1 - 0.2 mole % Majerus et al Science 234:1519-1526 report a huge range of concentrations: from 1 to 10% of PI content, which is in turn 2-8% of cell lipid. This gives 2e-4 to 8e-3 of cell lipid. In concentrations in total volume of cell (a somewhat strange number given the compartmental considerations) this comes to anywhere from 4 uM to 200 uM. PLA2 is stim 7x by PIP2 (Leslie and Channon BBA 1045:261(1990) Leslie and Channon say PIP2 is present at 0.1 - 0.2mol% range in membs, so I\'ll use a value at the lower end of the scale for basal PIP2.
constant: true
boundary condition: true
has only substance units: false
initial concentration: 2.5
initial amount: NaN
in compartment: 541094
type: Species

147703
local parameters: 352686
local parameters: 352684
notes: kf*AA-kb*PLA2_slash_APC
type: KineticLaw

352650
units: 146944
value: 8.6348E-12
type: LocalParameter

352961
units: 146944
value: 2.5E-11
type: LocalParameter

148611
stoichiometry: 1.0
species: 542511
type: SpeciesReference

151541
stoichiometry: 1.0
species: 542771
type: SpeciesReference

352670
units: 146944
value: 5.0E-11
type: LocalParameter

352908
units: 146908
value: 0.0666666666666667
type: LocalParameter

150405
stoichiometry: 1.0
species: 542131
type: SpeciesReference

149024
stoichiometry: 1.0
species: 541711
type: SpeciesReference

544991
kinetic law: 151553
product: 151541
reactant: 151529
reactant: 151517
notes: See MKP2-tyr-deph
fast: false
reversible: true
type: Reaction

149193
stoichiometry: 1.0
species: 541611
type: SpeciesReference

541711
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 541094
type: Species

147967
stoichiometry: 1.0
species: 542851
type: SpeciesReference

151553
local parameters: 353016
local parameters: 353014
notes: k1*MAPK_star_*MKP_minus_2-k2*MKP_minus_2_slash_MKP2_minus_thr_minus_deph_slash_MKP2_minus_thr_minus_deph_cplx
type: KineticLaw

150743
stoichiometry: 1.0
species: 542871
type: SpeciesReference

149862
local parameters: 352925
notes: k3*MAPK_star__slash_MAPK_star__minus_feedback_slash_MAPK_star__minus_feedback_cplx
type: KineticLaw

151457
local parameters: 353011
local parameters: 353009
notes: k1*MAPK_slash_MAPK_minus_tyr*MKP_minus_2-k2*MKP_minus_2_slash_MKP2_minus_tyr_minus_deph_slash_MKP2_minus_tyr_minus_deph_cplx
type: KineticLaw

543371
kinetic law: 147775
product: 147763
reactant: 147751
notes: Rate of turnover of phosph form of MKP1 is from Brondello et al Science 286:2514 1999. Tau is about 150 min though it is not a clean exponential falloff.
fast: false
reversible: true
type: Reaction

149521
local parameters: 352912
local parameters: 352911
notes: k1*MAPK_slash_Nucleotides*MAPK_slash_nuc_MAPK_star_-k2*MAPK_slash_nuc_MAPK_star__slash_act_transcription_slash_act_transcription_cplx
type: KineticLaw

149922
stoichiometry: 1.0
species: 542031
type: SpeciesReference

151263
local parameters: 353001
local parameters: 352999
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

150671
stoichiometry: 1.0
species: 542231
type: SpeciesReference

147388
stoichiometry: 1.0
species: 541351
type: SpeciesReference

147617
local parameters: 352678
local parameters: 352676
notes: kf*PKC_slash_PKC_minus_cytosolic*DAG-kb*PKC_slash_PKC_minus_DAG
type: KineticLaw

147068
stoichiometry: 1.0
species: 542691
type: SpeciesReference

352963
units: 146944
value: 6.0E-12
type: LocalParameter

148259
stoichiometry: 1.0
species: 542811
type: SpeciesReference

150333
stoichiometry: 1.0
species: 542091
type: SpeciesReference

352690
units: 146944
value: 0.0
type: LocalParameter

150477
stoichiometry: 1.0
species: 542151
type: SpeciesReference

352909
units: 146944
value: 1.0E-12
type: LocalParameter

148345
stoichiometry: 1.0
species: 542431
type: SpeciesReference

147992
local parameters: 352813
local parameters: 352812
notes: kf*MAPK_slash_Nucleotides-kb*MAPK_slash_MKP1_minus_RNA
type: KineticLaw

148455
stoichiometry: 1.0
species: 542491
type: SpeciesReference

543391
kinetic law: 147811
product: 147799
reactant: 147787
notes: Rate of turnover of phosph form of MKP1 is from Brondello et al Science 286:2514 1999. Tau is about 150 min though it is not a clean exponential falloff.
fast: false
reversible: true
type: Reaction

148745
local parameters: 352876
local parameters: 352874
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

544911
kinetic law: 151361
product: 151349
reactant: 151337
reactant: 151324
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. Tau 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. 27 Apr 2001: Lowered k3 to 0.05 to fix conc-effect of SHC phosph by PDGF. This gives results for downstream effects in agreement with other papers, e.g., the Brondello papers.
fast: false
reversible: true
type: Reaction

544271
kinetic law: 149812
product: 149800
reactant: 149788
reactant: 149775
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

148321
local parameters: 352839
local parameters: 352837
notes: kf*PLA2_slash_PLA2_star_-kb*PLA2_slash_PLA2_minus_cytosolic
type: KineticLaw

541631
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.36
initial amount: NaN
in compartment: 541094
type: Species

542171
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 541094
type: Species

352859
units: 146944
value: 1.0E-13
type: LocalParameter

543091
kinetic law: 147184
product: 147172
reactant: 147160
notes: The best 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

150056
local parameters: 352935
notes: k3*MAPK_star__slash_MKP_minus_1_minus_phosph_slash_MKP_minus_1_minus_phosph_cplx
type: KineticLaw

544411
kinetic law: 150153
product: 150141
product: 150129
reactant: 150117
fast: false
reversible: false
type: Reaction

147679
stoichiometry: 1.0
species: 541491
type: SpeciesReference

148479
local parameters: 352855
local parameters: 352853
notes: kf*MAPK_slash_craf_minus_1*Ras_slash_GTP_minus_Ras-kb*MAPK_slash_RGR
type: KineticLaw

543911
kinetic law: 148939
product: 148926
reactant: 148914
reactant: 148902
notes: Rate constants are generic PKC rates. See Chen SJ, Klann E, Gower MC, Powell CM, Sessoms JS, Sweatt JD. (1993) Biochemistry 32(4):1032-9. This reaction activates GEF. Gives >= 2X stim of ras, and a 2X stim of MAPK over amount from direct phosph of c-raf. Note that it is a push-pull reaction, and also get effect through phosph and inact of GAPs.
fast: false
reversible: true
type: Reaction

147496
stoichiometry: 1.0
species: 541471
type: SpeciesReference

148527
local parameters: 352859
local parameters: 352857
notes: kf*PDGFR_slash_PDGFR*PDGFR_slash_PDGF-kb*PDGFR_slash_L_dot_PDGFR
type: KineticLaw

352879
units: 146981
value: 1.875E-12
type: LocalParameter

148065
stoichiometry: 1.0
species: 542811
type: SpeciesReference

543351
kinetic law: 147739
product: 147727
reactant: 147715
notes: Rate of turnover of non-phosph form of MKP1 is from Brondello et al Science 286:2514 1999. Tau is about 45 min.
fast: false
reversible: true
type: Reaction

151044
stoichiometry: 1.0
species: 542371
type: SpeciesReference

149449
stoichiometry: 1.0
species: 541671
type: SpeciesReference

151080
stoichiometry: 1.0
species: 542391
type: SpeciesReference

541651
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 541094
type: Species

544931
kinetic law: 151409
product: 151397
product: 151385
reactant: 151373
fast: false
reversible: false
type: Reaction

543151
kinetic law: 147328
product: 147316
reactant: 147304
reactant: 147292
notes: Ca.PKC interaction with DAG is modeled by this reaction. Kf based on Shinomura et al PNAS 88 5149-5153 1991 and Schaechter and Benowitz 1993 J Neurosci 13(10):4361 and uses the constraining procedure referred to in the general notes for PKC.
fast: false
reversible: true
type: Reaction

149594
stoichiometry: 1.0
species: 541931
type: SpeciesReference

541851
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 541094
type: Species

150129
stoichiometry: 1.0
species: 541851
type: SpeciesReference

543951
kinetic law: 149036
product: 149024
reactant: 149012
reactant: 149000
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, ratio of 4 to get k2=0.6. k1=0.75/46.6nM=2.7e-5 In terms of Michaelis-Menten rates, Km = 0.046, Vmax = 0.15, ratio = 4.
fast: false
reversible: true
type: Reaction

543051
kinetic law: 147094
product: 147081
reactant: 147068
reactant: 147055
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

150996
stoichiometry: 1.0
species: 541491
type: SpeciesReference

544491
kinetic law: 150345
product: 150333
product: 150321
reactant: 150309
fast: false
reversible: false
type: Reaction

352796
units: 146944
value: 1.0E-16
type: LocalParameter

149048
stoichiometry: 1.0
species: 541711
type: SpeciesReference

544071
kinetic law: 149328
product: 149315
reactant: 149303
reactant: 149291
notes: Same kinetics as other c-raf activated forms. See Force et al PNAS 91 1270-1274 1994. k1 = 5.5e-6, k2 = .42, k3 = 0.105
fast: false
reversible: true
type: Reaction

544471
kinetic law: 150297
product: 150285
reactant: 150273
reactant: 150261
notes: See parent PPhosphatase2A for parms
fast: false
reversible: true
type: Reaction

543611
kinetic law: 148284
product: 148271
reactant: 148259
reactant: 148247
notes: Nemenoff et al 1993 JBC 268:1960 report a 2X to 4x activation of PLA2 by MAPK, which seems dependent on Ca as well. This reaction represents this activation. Rates are scaled to give appropriate fold activation.
fast: false
reversible: true
type: Reaction

541391
constant: false
boundary condition: false
has only substance units: false
initial concentration: 1.81333333333333E-17
initial amount: NaN
in compartment: 541094
type: Species

147208
stoichiometry: 1.0
species: 541251
type: SpeciesReference

148381
stoichiometry: 1.0
species: 542511
type: SpeciesReference

352640
units: 146981
value: 2.50002E-14
type: LocalParameter

543931
kinetic law: 148988
product: 148976
product: 148964
reactant: 148951
fast: false
reversible: false
type: Reaction

352630
units: 146944
value: 1.0E-13
type: LocalParameter

147581
stoichiometry: 1.0
species: 541471
type: SpeciesReference

150068
stoichiometry: 1.0
species: 541831
type: SpeciesReference

543551
kinetic law: 148137
product: 148125
reactant: 148113
reactant: 148101
notes: Activation of PLA2 by PIP2. From Leslie and Channon 1990 BBA 1045:261 the stimulation of PLA2 activity by high PIP2 is 7x. In this model we don\'t really expect any PIP2 stimulus.
fast: false
reversible: true
type: Reaction

541191
constant: false
boundary condition: false
has only substance units: false
initial concentration: 1.0
initial amount: NaN
in compartment: 541094
type: Species

148052
stoichiometry: 1.0
species: 542191
type: SpeciesReference

148149
stoichiometry: 1.0
species: 542891
type: SpeciesReference

149630
stoichiometry: 1.0
species: 541951
type: SpeciesReference

543251
kinetic law: 147520
product: 147508
reactant: 147496
notes: Basal activity of PKC is quite high, about 10% of max. See Schaechter and Benowitz 1993 J Neurosci 13(10):4361 and Shinomura et al 1991 PNAS 88:5149-5153. This is partly due to basal levels of DAG, AA and Ca, but even when these are taken into account (see the derivations as per the PKC general notes) there is a small basal activity still to be accounted for. This reaction handles it by giving a 2% activity at baseline.
fast: false
reversible: true
type: Reaction

147667
local parameters: 352682
local parameters: 352680
notes: kf*PKC_slash_PKC_minus_DAG*AA-kb*PKC_slash_PKC_minus_DAG_minus_AA
type: KineticLaw

148467
stoichiometry: 1.0
species: 541771
type: SpeciesReference

151349
stoichiometry: 1.0
species: 542631
type: SpeciesReference

542231
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 541094
type: Species

147629
stoichiometry: 1.0
species: 541431
type: SpeciesReference

352644
units: 146981
value: 6.0E-13
type: LocalParameter

545011
kinetic law: 151602
product: 151590
product: 151577
reactant: 151565
fast: false
reversible: false
type: Reaction

541093
constant: true
size: 1.0E-18
spatial dimensions: 3.0
type: Compartment

543211
kinetic law: 147448
product: 147436
reactant: 147424
reactant: 147412
notes: Ca-dependent AA activation of PKC. Note that this step combines the AA activation and also the membrane translocation. From Schaechter and Benowitz 1993 J Neurosci 13(10):4361
fast: false
reversible: true
type: Reaction

544891
kinetic law: 151311
product: 151299
product: 151287
reactant: 151275
fast: false
reversible: false
type: Reaction

148515
stoichiometry: 1.0
species: 542611
type: SpeciesReference

149230
local parameters: 352901
local parameters: 352899
notes: k1*MAPK_slash_MAPKK*MAPK_slash_RGR-k2*MAPK_slash_RGR_slash_RGR_dot_1_slash_RGR_dot_1_cplx
type: KineticLaw

147484
local parameters: 352666
local parameters: 352664
notes: kf*PKC_slash_PKC_minus_DAG_minus_AA-kb*PKC_slash_PKC_minus_DAG_minus_AA_star_
type: KineticLaw

544171
kinetic law: 149570
product: 149558
product: 149546
reactant: 149533
fast: false
reversible: false
type: Reaction

150369
stoichiometry: 1.0
species: 542091
type: SpeciesReference

150900
stoichiometry: 1.0
species: 541491
type: SpeciesReference

352658
units: 146944
value: 1.0E-13
type: LocalParameter

151032
stoichiometry: 1.0
species: 542871
type: SpeciesReference

151092
stoichiometry: 1.0
species: 541491
type: SpeciesReference

149533
stoichiometry: 1.0
species: 541891
type: SpeciesReference

541291
constant: false
boundary condition: false
has only substance units: false
initial concentration: 4.91366666666667E-18
initial amount: NaN
in compartment: 541094
type: Species

542031
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 541094
type: Species

150984
stoichiometry: 1.0
species: 542351
type: SpeciesReference

543971
kinetic law: 149084
product: 149072
product: 149060
reactant: 149048
fast: false
reversible: false
type: Reaction

542951
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 541094
type: Species

541094
constant: true
size: 1.0E-12
spatial dimensions: 3.0
type: Compartment

148732
stoichiometry: 1.0
species: 541516
type: SpeciesReference

544131
kinetic law: 149473
modifier: 149461
product: 149449
reactant: 149437
notes: 3 Feb 2000. Same rates as MKP1
fast: false
reversible: false
type: Reaction

352642
units: 146944
value: 1.68E-14
type: LocalParameter

149546
stoichiometry: 1.0
species: 541911
type: SpeciesReference

542971
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 541094
type: Species

543291
kinetic law: 147617
product: 147605
reactant: 147593
reactant: 147581
notes: Binding of PKC to DAG, non-Ca dependent. Kf based on Shinomura et al PNAS 88 5149-5153 1991 Tau estimated as fast and here it is about the same time-course as the formation of DAG so it will not be rate-limiting.
fast: false
reversible: true
type: Reaction

148137
local parameters: 352823
local parameters: 352822
notes: kf*temp_minus_PIP2*PLA2_slash_PLA2_minus_cytosolic-kb*PLA2_slash_PIP2_minus_PLA2_star_
type: KineticLaw

147081
stoichiometry: 1.0
species: 541131
type: SpeciesReference

148393
local parameters: 352847
local parameters: 352845
notes: kf*Ras_slash_GTP_minus_Ras-kb*Ras_slash_GDP_minus_Ras
type: KineticLaw

543991
kinetic law: 149133
product: 149121
reactant: 149108
reactant: 149096
notes: Rate consts same as for MAPKKtyr.
fast: false
reversible: true
type: Reaction

541991
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 541094
type: Species

150453
stoichiometry: 1.0
species: 541751
type: SpeciesReference

542131
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 541094
type: Species

150381
stoichiometry: 1.0
species: 542131
type: SpeciesReference

352646
units: 146944
value: 5.0E-13
type: LocalParameter

151020
local parameters: 352988
notes: k3*PLA2_slash_DAG_minus_Ca_minus_PLA2_star__slash_kenz_slash_kenz_cplx
type: KineticLaw

352855
units: 146944
value: 1.0E-12
type: LocalParameter

544771
kinetic law: 151020
product: 151008
product: 150996
reactant: 150984
fast: false
reversible: false
type: Reaction

150357
stoichiometry: 1.0
species: 541691
type: SpeciesReference

149242
stoichiometry: 1.0
species: 541791
type: SpeciesReference

543811
kinetic law: 148695
product: 148683
product: 148671
reactant: 148659
fast: false
reversible: false
type: Reaction

149570
local parameters: 352913
notes: k3*MAPK_slash_nuc_MAPK_star__slash_act_transcription_slash_act_transcription_cplx
type: KineticLaw

544831
kinetic law: 151165
product: 151153
reactant: 151141
reactant: 151129
notes: Kinetics from Orita et al JBC 268(34):25542-25546. Note that the Vmax is slow, but it does match the slow GTP hydrolysis rates.
fast: false
reversible: true
type: Reaction

352636
units: 146944
value: 1.0E-15
type: LocalParameter

352869
units: 146981
value: 1.98E-13
type: LocalParameter

151337
stoichiometry: 1.0
species: 542611
type: SpeciesReference

148769
stoichiometry: 1.0
species: 541591
type: SpeciesReference

541911
constant: false
boundary condition: false
has only substance units: false
initial concentration: 1.0E-4
initial amount: NaN
in compartment: 541111
type: Species

352656
units: 146944
value: 1.0E-12
type: LocalParameter

542111
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 541094
type: Species

353006
units: 146944
value: 2.0E-13
type: LocalParameter

149642
stoichiometry: 1.0
species: 541751
type: SpeciesReference

352666
units: 146944
value: 2.0E-13
type: LocalParameter

541971
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 541094
type: Species

352841
units: 146944
value: 1.0E-13
type: LocalParameter

544791
kinetic law: 151068
product: 151056
reactant: 151044
reactant: 151032
notes: This form should be 3 to 6 times as fast as the Ca-only form, from Lin et al 1993 Cell 269-278 Nemenoff et al 1993 JBC 268:1960 Several forms contribute to the Ca-stimulated form, so this rate has to be a factor larger than their total contribution. I assign Vmax as the scale factor here because there is lots of APC substrate, so all the PLA2 complex enzymes are limited primarily by Vmax.
fast: false
reversible: true
type: Reaction

148853
stoichiometry: 1.0
species: 541531
type: SpeciesReference

544751
kinetic law: 150972
product: 150960
reactant: 150948
reactant: 150936
notes: Based on Leslie and Channon 1990 BBA 1045:261.
fast: false
reversible: true
type: Reaction

352664
units: 146944
value: 2.0E-12
type: LocalParameter

352654
units: 146944
value: 3.5026E-12
type: LocalParameter

353008
units: 146944
value: 5.0E-14
type: LocalParameter

147871
stoichiometry: 1.0
species: 541831
type: SpeciesReference

541931
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 541094
type: Species

149558
stoichiometry: 1.0
species: 541871
type: SpeciesReference

148125
stoichiometry: 1.0
species: 542251
type: SpeciesReference

150888
stoichiometry: 1.0
species: 542311
type: SpeciesReference

149703
stoichiometry: 1.0
species: 541971
type: SpeciesReference

151602
local parameters: 353018
notes: k3*MKP_minus_2_slash_MKP2_minus_thr_minus_deph_slash_MKP2_minus_thr_minus_deph_cplx
type: KineticLaw

541951
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 541094
type: Species

150043
stoichiometry: 1.0
species: 541991
type: SpeciesReference

544731
kinetic law: 150924
product: 150912
product: 150900
reactant: 150888
fast: false
reversible: false
type: Reaction

150972
local parameters: 352986
local parameters: 352984
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

149582
stoichiometry: 1.0
species: 541611
type: SpeciesReference

352648
units: 146981
value: 7.9998E-15
type: LocalParameter

352857
units: 146981
value: 1.99998E-10
type: LocalParameter

352634
units: 146944
value: 1.68E-14
type: LocalParameter

150465
stoichiometry: 1.0
species: 542091
type: SpeciesReference

352867
units: 146944
value: 6.6E-16
type: LocalParameter

149254
stoichiometry: 1.0
species: 541751
type: SpeciesReference

353009
units: 146981
value: 7.5E-11
type: LocalParameter

542831
notes: This is a representation of generic ubiquitination followed by degradation. Since this pool is buffered to zero, anything that ends up here is removed from the model.
constant: true
boundary condition: true
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 541094
type: Species

151008
stoichiometry: 1.0
species: 542331
type: SpeciesReference

541371
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.02
initial amount: NaN
in compartment: 541094
type: Species

542551
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.002
initial amount: NaN
in compartment: 541094
type: Species

148841
local parameters: 352881
local parameters: 352879
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

148757
stoichiometry: 1.0
species: 541516
type: SpeciesReference

150030
stoichiometry: 1.0
species: 541831
type: SpeciesReference

352668
units: 146944
value: 1.0E-12
type: LocalParameter

149654
stoichiometry: 1.0
species: 541931
type: SpeciesReference

148671
stoichiometry: 1.0
species: 542491
type: SpeciesReference

147835
stoichiometry: 1.0
species: 542072
type: SpeciesReference

147593
stoichiometry: 1.0
species: 542791
type: SpeciesReference

148113
stoichiometry: 1.0
species: 542191
type: SpeciesReference

148040
local parameters: 352816
local parameters: 352815
notes: kf*MAPK_slash_craf_minus_1_star_*Ras_slash_GTP_minus_Ras-kb*MAPK_slash_Raf_star__minus_GTP_minus_Ras
type: KineticLaw

542871
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. For now it is treated as a buffered metabolite.
constant: true
boundary condition: true
has only substance units: false
initial concentration: 30.0
initial amount: NaN
in compartment: 541094
type: Species

543891
kinetic law: 148890
product: 148878
product: 148865
reactant: 148853
fast: false
reversible: false
type: Reaction

541331
constant: false
boundary condition: false
has only substance units: false
initial concentration: 1.3896E-17
initial amount: NaN
in compartment: 541094
type: Species

352652
units: 146944
value: 1.2705E-12
type: LocalParameter

541231
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 541094
type: Species

148539
stoichiometry: 1.0
species: 542691
type: SpeciesReference

150960
stoichiometry: 1.0
species: 542351
type: SpeciesReference

147520
local parameters: 352670
local parameters: 352668
notes: kf*PKC_slash_PKC_minus_cytosolic-kb*PKC_slash_PKC_minus_basal_star_
type: KineticLaw

352632
units: 146981
value: 2.50002E-14
type: LocalParameter

150876
local parameters: 352981
local parameters: 352979
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

151324
stoichiometry: 1.0
species: 542671
type: SpeciesReference

353016
units: 146944
value: 4.0E-12
type: LocalParameter

149751
stoichiometry: 1.0
species: 541931
type: SpeciesReference

542191
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.4
initial amount: NaN
in compartment: 541094
type: Species

541171
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 541094
type: Species

543571
kinetic law: 148185
product: 148173
reactant: 148161
reactant: 148149
notes: Synergistic activation of PLA2 by Ca and PIP2. Again from Leslie and Channon 1990 BBA 1045:261
fast: false
reversible: true
type: Reaction

150864
stoichiometry: 1.0
species: 542311
type: SpeciesReference

151214
local parameters: 352998
notes: k3*Ras_slash_GEF_star__slash_GEF_star__minus_act_minus_ras_slash_GEF_star__minus_act_minus_ras_cplx
type: KineticLaw

150501
stoichiometry: 1.0
species: 542151
type: SpeciesReference

150561
stoichiometry: 1.0
species: 542091
type: SpeciesReference

148878
stoichiometry: 1.0
species: 542931
type: SpeciesReference

147508
stoichiometry: 1.0
species: 541371
type: SpeciesReference

544251
kinetic law: 149763
product: 149751
product: 149739
reactant: 149727
fast: false
reversible: false
type: Reaction

352804
units: 146981
value: 1.00002E-14
type: LocalParameter

148491
stoichiometry: 1.0
species: 542591
type: SpeciesReference

543711
kinetic law: 148479
product: 148467
reactant: 148455
reactant: 148442
notes: Based on rates of Ras-act-craf which has Kf=60, Kb= 0.5. This reaction was introduced to account for the PKC-independent activation of MAPK. This reac should have less affinity but similar tau as compared to the Ras-cat-craf, since the phosphorylated Raf form has a greater effect on MAPK.
fast: false
reversible: true
type: Reaction

352812
units: 146944
value: 1.0E-18
type: LocalParameter

543171
kinetic law: 147364
product: 147352
reactant: 147340
notes: Membrane translocation is a standard step in PKC activation. It also turns out to be necessary to replicate the curves from Schaechter and Benowitz 1993 J Neurosci 13(10):4361 and Shonomura et al 1991 PNAS 88:5149-5153. These rates are constrained by matching the curves in the above papers and by fixing a rather fast (sub-second) tau for PKC activation.
fast: false
reversible: true
type: Reaction

352865
units: 146944
value: 1.0E-15
type: LocalParameter

543731
kinetic law: 148527
product: 148515
reactant: 148503
reactant: 148491
notes: From Heidaran et al JBC268(13):9287 Fig 5. Kd is ~0.5 nM
fast: false
reversible: true
type: Reaction

149365
stoichiometry: 1.0
species: 541771
type: SpeciesReference

148101
stoichiometry: 1.0
species: 542891
type: SpeciesReference

352884
units: 146981
value: 3.0E-13
type: LocalParameter

147847
local parameters: 352797
local parameters: 352796
notes: kf*MAPK_slash_MKP_minus_1_minus_ser359_star_-kb*MKP_minus_1
type: KineticLaw

148683
stoichiometry: 1.0
species: 541131
type: SpeciesReference

541831
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 541094
type: Species

151177
stoichiometry: 1.0
species: 542471
type: SpeciesReference

352851
units: 146944
value: 0.0
type: LocalParameter

150201
local parameters: 352943
local parameters: 352941
notes: kcat*MKP_minus_1*MAPK_slash_MAPK_minus_tyr/(Km+MAPK_slash_MAPK_minus_tyr)
type: KineticLaw

544291
kinetic law: 149862
product: 149850
product: 149837
reactant: 149824
fast: false
reversible: false
type: Reaction

151104
stoichiometry: 1.0
species: 542371
type: SpeciesReference

543131
kinetic law: 147280
product: 147268
reactant: 147256
reactant: 147244
notes: This Kd is a straightforward result from the Schaechter and Benowitz 1993 J Neurosci 13(10):4361 curves. The time-course is based on the known rapid activation of PKC and also the fact that Ca association with proteins is typically quite fast. My guess is that this tau of 2 sec is quite conservative and the actualy rate may be much faster. The parameter is quite insensitive for most stimuli.
fast: false
reversible: true
type: Reaction

151493
stoichiometry: 1.0
species: 542731
type: SpeciesReference

352825
units: 146981
value: 1.2E-14
type: LocalParameter

149812
local parameters: 352923
local parameters: 352921
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

541751
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 541094
type: Species

352886
units: 146944
value: 1.6E-11
type: LocalParameter

353003
units: 146944
value: 1.0E-11
type: LocalParameter

147533
stoichiometry: 1.0
species: 541491
type: SpeciesReference

541871
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 541111
type: Species

543071
kinetic law: 147147
product: 147134
reactant: 147121
reactant: 147107
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 phosphorylation.
fast: false
reversible: true
type: Reaction

148805
stoichiometry: 1.0
species: 542551
type: SpeciesReference

149401
stoichiometry: 1.0
species: 541631
type: SpeciesReference

541771
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 541094
type: Species

149266
stoichiometry: 1.0
species: 541771
type: SpeciesReference

148185
local parameters: 352827
local parameters: 352825
notes: kf*temp_minus_PIP2*PLA2_slash_PLA2_minus_Ca_star_-kb*PLA2_slash_PIP2_minus_Ca_minus_PLA2_star_
type: KineticLaw

148016
stoichiometry: 1.0
species: 542491
type: SpeciesReference

352831
units: 146944
value: 4.0E-12
type: LocalParameter

352845
units: 146944
value: 1.0E-16
type: LocalParameter

544551
kinetic law: 150489
product: 150477
reactant: 150465
reactant: 150453
notes: See parent PPhostphatase2A description for rate details
fast: false
reversible: true
type: Reaction

352871
units: 146944
value: 8.0E-14
type: LocalParameter

150707
stoichiometry: 1.0
species: 541491
type: SpeciesReference

353018
units: 146944
value: 1.0E-12
type: LocalParameter

150273
stoichiometry: 1.0
species: 542091
type: SpeciesReference

543531
kinetic law: 148089
product: 148077
reactant: 148065
reactant: 148052
notes: Direct activation of PLA2 by Ca. From Leslie and Channon BBA 1045 (1990) 261-270 fig6 pp267.
fast: false
reversible: true
type: Reaction

150936
stoichiometry: 1.0
species: 542871
type: SpeciesReference

352931
units: 146981
value: 1.95E-13
type: LocalParameter

353014
units: 146981
value: 7.5E-11
type: LocalParameter

149763
local parameters: 352919
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

151117
local parameters: 352993
notes: k3*PLA2_slash_PLA2_star__minus_Ca_slash_kenz_slash_kenz_cplx
type: KineticLaw

151226
stoichiometry: 1.0
species: 542491
type: SpeciesReference

353004
units: 146981
value: 3.0E-13
type: LocalParameter

544371
kinetic law: 150056
product: 150043
product: 150030
reactant: 150018
fast: false
reversible: false
type: Reaction

150513
stoichiometry: 1.0
species: 541611
type: SpeciesReference

150852
stoichiometry: 1.0
species: 542291
type: SpeciesReference

150573
stoichiometry: 1.0
species: 542171
type: SpeciesReference

542211
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 541094
type: Species

147859
stoichiometry: 1.0
species: 541851
type: SpeciesReference

148695
local parameters: 352873
notes: k3*Shc_star__dot_Sos_dot_Grb2_slash_Sos_dot_Ras_GEF_slash_Sos_dot_Ras_GEF_cplx
type: KineticLaw

544351
kinetic law: 150006
product: 149994
reactant: 149982
reactant: 149970
notes: 3 Feb 2000. See Brondello et al Science 286:2514 1999. Rates assumed standard MAPK rates based on Sanghera et al JBC 265(1):53-57 1990. The Vmax is scaled down 10 fold to match the time-course of phosph by MAPK, from the Brondello paper.
fast: false
reversible: true
type: Reaction

542591
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.108333333333333
initial amount: NaN
in compartment: 541094
type: Species

151165
local parameters: 352996
local parameters: 352994
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

352638
units: 146944
value: 0.0
type: LocalParameter

352853
units: 146981
value: 6.0E-12
type: LocalParameter

148781
stoichiometry: 1.0
species: 542931
type: SpeciesReference

352911
units: 146981
value: 1.999992E-16
type: LocalParameter

544871
kinetic law: 151263
product: 151250
reactant: 151238
reactant: 151226
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%). The two sets of values are reasonably close. k1 = 1.666e-3/sec, k2 = 1000/sec, k3 = 10/sec (note k3 is rate-limiting) This is one of the rare cases where we have direct info on the k3 being rate-limiting. Hence the ratio I use for the k2:k3 rates is 100 rather than the usual 4.
fast: false
reversible: true
type: Reaction

352676
units: 146981
value: 6.0E-16
type: LocalParameter

149473
local parameters: 352910
local parameters: 352909
notes: kcat*MAPK_slash_MKP_minus_1_star__star_*MAPK_star_/(Km+MAPK_star_)
type: KineticLaw

352678
units: 146944
value: 1.0E-13
type: LocalParameter

149800
stoichiometry: 1.0
species: 542011
type: SpeciesReference

151311
local parameters: 353003
notes: k3*Ras_slash_GAP_slash_GAP_minus_inact_minus_ras_slash_GAP_minus_inact_minus_ras_cplx
type: KineticLaw

148865
stoichiometry: 1.0
species: 542531
type: SpeciesReference

544151
kinetic law: 149521
product: 149509
reactant: 149497
reactant: 149485
notes: This is a \'black box\' representation of a lot of steps. Constraint provided by determining rate of formation of MKP-1.
fast: false
reversible: true
type: Reaction

147268
stoichiometry: 1.0
species: 541271
type: SpeciesReference

147545
stoichiometry: 1.0
species: 541471
type: SpeciesReference

352930
units: 146944
value: 2.0E-11
type: LocalParameter

352823
units: 146944
value: 5.0E-13
type: LocalParameter

147121
stoichiometry: 1.0
species: 541191
type: SpeciesReference

352863
units: 146944
value: 0.0
type: LocalParameter

352805
units: 146944
value: 1.0E-15
type: LocalParameter

542291
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 541094
type: Species

542451
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 541094
type: Species

352813
units: 146944
value: 0.0
type: LocalParameter

542251
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 541094
type: Species

352833
units: 146981
value: 6.0E-12
type: LocalParameter

352883
units: 146944
value: 2.5E-11
type: LocalParameter

150948
stoichiometry: 1.0
species: 542331
type: SpeciesReference

150285
stoichiometry: 1.0
species: 542111
type: SpeciesReference

352910
units: 146908
value: 0.0666666666666667
type: LocalParameter

149352
stoichiometry: 1.0
species: 541691
type: SpeciesReference

543271
kinetic law: 147569
product: 147557
reactant: 147545
reactant: 147533
notes: AA stimulates PKC activity even at rather low Ca. Schaechter and Benowitz 1993 J Neurosci 13(10):4361 Note that this one reaction combines the initial interaction and also membrane translocation.
fast: false
reversible: true
type: Reaction

148197
stoichiometry: 1.0
species: 542791
type: SpeciesReference

542431
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.1
initial amount: NaN
in compartment: 541094
type: Species

148004
stoichiometry: 1.0
species: 541591
type: SpeciesReference

352873
units: 146944
value: 2.0E-14
type: LocalParameter

149278
local parameters: 352903
notes: k3*MAPK_slash_RGR_slash_RGR_dot_1_slash_RGR_dot_1_cplx
type: KineticLaw

352843
units: 146944
value: 0.0
type: LocalParameter

352949
units: 146981
value: 1.98E-12
type: LocalParameter

148793
local parameters: 352878
notes: k3*PKC_minus_active_slash_PKC_minus_act_minus_raf_slash_PKC_minus_act_minus_raf_cplx
type: KineticLaw

352889
units: 146981
value: 1.62E-11
type: LocalParameter

352923
units: 146944
value: 4.0E-11
type: LocalParameter

352822
units: 146981
value: 1.2E-15
type: LocalParameter

150309
stoichiometry: 1.0
species: 542111
type: SpeciesReference

151153
stoichiometry: 1.0
species: 542471
type: SpeciesReference

148271
stoichiometry: 1.0
species: 542371
type: SpeciesReference

543831
kinetic law: 148745
product: 148732
reactant: 148720
reactant: 148707
notes: Rate consts from Chen et al Biochem 32, 1032 (1993) k3 = 4 Km for this substrate is trickier. Specific substrates are in the uM range, so we use a higher Km here. This may be too conservative in which case PKC would have a still higher effect on raf. The presence of this phosphorylation and activation step is from Kolch et al 1993 Nature 364:249
fast: false
reversible: true
type: Reaction

149389
stoichiometry: 1.0
species: 541671
type: SpeciesReference

352933
units: 146944
value: 4.0E-12
type: LocalParameter

151129
stoichiometry: 1.0
species: 542511
type: SpeciesReference

150165
stoichiometry: 1.0
species: 541671
type: SpeciesReference

352874
units: 146981
value: 3.0E-13
type: LocalParameter

148720
stoichiometry: 1.0
species: 542931
type: SpeciesReference

544211
kinetic law: 149667
product: 149654
product: 149642
reactant: 149630
fast: false
reversible: false
type: Reaction

149775
stoichiometry: 1.0
species: 541591
type: SpeciesReference

148599
local parameters: 352867
local parameters: 352865
notes: kf*PDGFR_slash_L_dot_PDGFR-kb*PDGFR_slash_Internal_L_dot_PDGFR
type: KineticLaw

147472
stoichiometry: 1.0
species: 541291
type: SpeciesReference

149425
local parameters: 352908
local parameters: 352907
notes: kcat*MAPK_slash_MKP_minus_1_star__star_*MAPK_slash_MAPK_minus_tyr/(Km+MAPK_slash_MAPK_minus_tyr)
type: KineticLaw

149837
stoichiometry: 1.0
species: 541651
type: SpeciesReference

352861
units: 146944
value: 1.0E-14
type: LocalParameter

148089
local parameters: 352820
local parameters: 352818
notes: kf*PLA2_slash_PLA2_minus_cytosolic*Ca-kb*PLA2_slash_PLA2_minus_Ca_star_
type: KineticLaw

148161
stoichiometry: 1.0
species: 542211
type: SpeciesReference

150912
stoichiometry: 1.0
species: 542291
type: SpeciesReference

352876
units: 146944
value: 1.6E-11
type: LocalParameter

353013
units: 146944
value: 1.0E-12
type: LocalParameter

147316
stoichiometry: 1.0
species: 541411
type: SpeciesReference

149788
stoichiometry: 1.0
species: 541991
type: SpeciesReference

352849
units: 146944
value: 1.0E-13
type: LocalParameter

148418
stoichiometry: 1.0
species: 542551
type: SpeciesReference

150104
local parameters: 352938
local parameters: 352936
notes: k1*MAPK_slash_MKP_minus_1_minus_ser359_star_*MAPK_star_-k2*MAPK_star__slash_MKP_minus_1_minus_phosph2_slash_MKP_minus_1_minus_phosph2_cplx
type: KineticLaw

147641
stoichiometry: 1.0
species: 541491
type: SpeciesReference

542391
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 541094
type: Species

544811
kinetic law: 151117
product: 151104
product: 151092
reactant: 151080
fast: false
reversible: false
type: Reaction

352835
units: 146944
value: 1.0E-13
type: LocalParameter

147557
stoichiometry: 1.0
species: 541391
type: SpeciesReference

352810
units: 146944
value: 0.0
type: LocalParameter

150598
stoichiometry: 1.0
species: 542171
type: SpeciesReference

151141
stoichiometry: 1.0
species: 542451
type: SpeciesReference

352921
units: 146981
value: 1.95E-12
type: LocalParameter

541211
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 541094
type: Species

543671
kinetic law: 148393
product: 148381
reactant: 148369
notes: This is extremely slow (kf = 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 There is no back reaction as we assume this to be a regular irreversible Michaelis-Menten zeroth order hydrolysis.
fast: false
reversible: true
type: Reaction

149377
local parameters: 352906
notes: k3*MAPK_slash_RGR_slash_RGR_dot_2_slash_RGR_dot_2_cplx
type: KineticLaw

352820
units: 146944
value: 1.0E-13
type: LocalParameter

352935
units: 146944
value: 1.0E-12
type: LocalParameter

543691
kinetic law: 148430
product: 148418
reactant: 148405
notes: Assume a reasonably good rate for dephosphorylating it, 0.1/sec. This fits well with resting levels of active kinase and the degree of activation as well as time-course of turnoff of Ras activation, but data is quite indirect.
fast: false
reversible: true
type: Reaction

151189
stoichiometry: 1.0
species: 542491
type: SpeciesReference

542571
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 541094
type: Species

151202
stoichiometry: 1.0
species: 542451
type: SpeciesReference

150117
stoichiometry: 1.0
species: 542071
type: SpeciesReference

150177
stoichiometry: 1.0
species: 541631
type: SpeciesReference

541551
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 541094
type: Species

541351
constant: false
boundary condition: false
has only substance units: false
initial concentration: 9.43516666666667E-21
initial amount: NaN
in compartment: 541094
type: Species

542851
notes: Infinite supply assumed for formation of mRNA.
constant: true
boundary condition: true
has only substance units: false
initial concentration: 0.1
initial amount: NaN
in compartment: 541111
type: Species

147654
stoichiometry: 1.0
species: 541451
type: SpeciesReference

543871
kinetic law: 148841
product: 148829
reactant: 148817
reactant: 148805
notes: Rate consts are PKC generic rates. This reaction inactivates GAP. The reaction is from the Boguski and McCormick 1993 review in Nature 366:643-654 The phosphorylation Vmax is 6x higher to account for balance of GDP-Ras:GDP-Ras.
fast: false
reversible: true
type: Reaction

149509
stoichiometry: 1.0
species: 541891
type: SpeciesReference

150261
stoichiometry: 1.0
species: 541591
type: SpeciesReference

148405
stoichiometry: 1.0
species: 542531
type: SpeciesReference

150659
stoichiometry: 1.0
species: 542211
type: SpeciesReference

148284
local parameters: 352835
local parameters: 352833
notes: kf*PLA2_slash_PLA2_star_*Ca-kb*PLA2_slash_PLA2_star__minus_Ca
type: KineticLaw

150719
stoichiometry: 1.0
species: 542211
type: SpeciesReference

352888
units: 146944
value: 4.0E-12
type: LocalParameter

150924
local parameters: 352983
notes: k3*PLA2_slash_PIP2_minus_Ca_minus_PLA2_star__slash_kenz_slash_kenz_cplx
type: KineticLaw

353001
units: 146944
value: 1.0E-9
type: LocalParameter

352878
units: 146944
value: 4.0E-12
type: LocalParameter

353011
units: 146944
value: 4.0E-12
type: LocalParameter

542531
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 541094
type: Species

147460
stoichiometry: 1.0
species: 541451
type: SpeciesReference

148173
stoichiometry: 1.0
species: 542291
type: SpeciesReference

148077
stoichiometry: 1.0
species: 542211
type: SpeciesReference

352809
units: 146944
value: 4.0E-16
type: LocalParameter

149437
stoichiometry: 1.0
species: 541991
type: SpeciesReference

147569
local parameters: 352674
local parameters: 352672
notes: kf*AA*PKC_slash_PKC_minus_cytosolic-kb*PKC_slash_PKC_minus_AA_star_
type: KineticLaw

149824
stoichiometry: 1.0
species: 542011
type: SpeciesReference

541811
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 541094
type: Species

352847
units: 146944
value: 0.0
type: LocalParameter

541251
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.1
initial amount: NaN
in compartment: 541094
type: Species

147328
local parameters: 352650
local parameters: 352648
notes: kf*DAG*PKC_slash_PKC_minus_Ca-kb*PKC_slash_PKC_minus_Ca_minus_DAG
type: KineticLaw

543511
kinetic law: 148040
product: 148028
reactant: 148016
reactant: 148004
notes: Assume binding is fast and limited only by available Ras*. 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 about 1e-4, giving a Kf of 60 for Kb of 0.5 and a tau of approx 2 sec. Based on: Hallberg et al JBC 269:6 3913-3916 1994, 3% of cellular Raf is complexed with Ras. This step needed to memb-anchor and activate Raf: Leevers et al Nature 369 411-414. Also see Koide et al 1993 PNAS USA 90(18):8683-8686
fast: false
reversible: true
type: Reaction

352837
units: 146944
value: 1.7E-13
type: LocalParameter