160236
stoichiometry: 1.0
species: 867299
type: SpeciesReference

159848
stoichiometry: 1.0
species: 868039
type: SpeciesReference

161462
stoichiometry: 1.0
species: 867479
type: SpeciesReference

868939
kinetic law: 161813
product: 161801
product: 161789
reactant: 161777
fast: false
reversible: false
type: Reaction

162514
stoichiometry: 1.0
species: 867779
type: SpeciesReference

161546
stoichiometry: 1.0
species: 867460
type: SpeciesReference

867360
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.36
initial amount: NaN
in compartment: 867160
type: Species

867699
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 867160
type: Species

867379
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 867160
type: Species

258990
units: 159727
value: 1.6E-11
type: LocalParameter

867959
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.2
initial amount: NaN
in compartment: 867160
type: Species

162793
stoichiometry: 1.0
species: 867939
type: SpeciesReference

867660
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 867160
type: Species

867320
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 867160
type: Species

867999
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.002
initial amount: NaN
in compartment: 867160
type: Species

259107
units: 159763
value: 9.996E-10
type: LocalParameter

258950
units: 159727
value: 2.0E-13
type: LocalParameter

867339
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.2
initial amount: NaN
in compartment: 867160
type: Species

258970
units: 159727
value: 4.0E-12
type: LocalParameter

160648
stoichiometry: 1.0
species: 867879
type: SpeciesReference

160673
stoichiometry: 1.0
species: 867939
type: SpeciesReference

160917
stoichiometry: 1.0
species: 868099
type: SpeciesReference

162418
stoichiometry: 1.0
species: 867739
type: SpeciesReference

869339
kinetic law: 162781
product: 162769
product: 162757
reactant: 162745
fast: false
reversible: false
type: Reaction

160844
stoichiometry: 1.0
species: 867999
type: SpeciesReference

161279
local parameters: 259014
local parameters: 259011
notes: k1*MAPK_slash_MAPKK*MAPK_slash_Raf_minus_GTP_minus_Ras_star_-k2*MAPK_slash_Raf_minus_GTP_minus_Ras_star__slash_Raf_minus_GTP_minus_Ras_star__dot_1_slash_Raf_minus_GTP_minus_Ras_star__dot_1_cplx
type: KineticLaw

868319
kinetic law: 160358
product: 160346
reactant: 160334
reactant: 160322
notes: Leslie and Channon BBA 1045 (1990) 261-270 fig6 pp267.
fast: false
reversible: true
type: Reaction

869199
kinetic law: 162442
product: 162430
reactant: 162418
reactant: 162406
notes: 10 x raise oct 22 12 x and rescale for k2 = 4 * k3 convention oct 24 Increase further to get the match to expt, which was spoilt due to large accumulation of PLA2 in the enzyme complexed forms. Lets raise k3, leaving the others at k1 = 1.5e-5 and k2 = 144 since they are large already.
fast: false
reversible: true
type: Reaction

867260
constant: false
boundary condition: false
has only substance units: false
initial concentration: 1.16101666666667E-16
initial amount: NaN
in compartment: 867160
type: Species

161558
stoichiometry: 1.0
species: 867480
type: SpeciesReference

868179
kinetic law: 159957
product: 159945
reactant: 159933
fast: false
reversible: true
type: Reaction

867899
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 867160
type: Species

161510
stoichiometry: 1.0
species: 867460
type: SpeciesReference

867460
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 867160
type: Species

161450
stoichiometry: 1.0
species: 867460
type: SpeciesReference

162841
stoichiometry: 1.0
species: 868001
type: SpeciesReference

160831
local parameters: 258988
notes: k3*PKC_minus_active_slash_PKC_minus_act_minus_raf_slash_PKC_minus_act_minus_raf_cplx
type: KineticLaw

162781
local parameters: 259105
notes: k3*Ras_slash_GEF_star__slash_GEF_star__minus_act_minus_ras_slash_GEF_star__minus_act_minus_ras_cplx
type: KineticLaw

160248
stoichiometry: 1.0
species: 867279
type: SpeciesReference

868199
kinetic law: 160041
product: 160029
reactant: 160017
reactant: 160005
notes: Schaechter and Benowitz We have to increase Kf for conc scaling Changed kf to 2e-9 on Sept 19, 94. This gives better match.
fast: false
reversible: true
type: Reaction

162502
stoichiometry: 1.0
species: 868059
type: SpeciesReference

160479
stoichiometry: 1.0
species: 867660
type: SpeciesReference

867179
constant: false
boundary condition: false
has only substance units: false
initial concentration: 3.72083333333333E-17
initial amount: NaN
in compartment: 867160
type: Species

160929
local parameters: 258991
notes: k3*PKC_minus_active_slash_PKC_minus_inact_minus_GAP_slash_PKC_minus_inact_minus_GAP_cplx
type: KineticLaw

160771
stoichiometry: 1.0
species: 867300
type: SpeciesReference

162091
stoichiometry: 1.0
species: 867559
type: SpeciesReference

867619
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 867160
type: Species

160636
stoichiometry: 1.0
species: 867899
type: SpeciesReference

160685
stoichiometry: 1.0
species: 867959
type: SpeciesReference

869119
kinetic law: 162247
product: 162235
reactant: 162223
reactant: 162211
notes: 10 x raise oct22 12 x oct 24, set k2 = 4 * k3
fast: false
reversible: true
type: Reaction

161522
local parameters: 259027
notes: k3*MAPK_star__slash_MAPK_star__minus_feedback_slash_MAPK_star__minus_feedback_cplx
type: KineticLaw

161207
stoichiometry: 1.0
species: 867460
type: SpeciesReference

162296
local parameters: 259075
notes: k3*PLA2_slash_PLA2_minus_Ca_star__slash_kenz_slash_kenz_cplx
type: KineticLaw

259104
units: 159727
value: 8.0E-14
type: LocalParameter

160698
local parameters: 258983
local parameters: 258982
notes: kf*Ras_slash_GTP_minus_Ras-kb*Ras_slash_GDP_minus_Ras
type: KineticLaw

869099
kinetic law: 162199
product: 162187
product: 162175
reactant: 162163
fast: false
reversible: false
type: Reaction

868079
notes: This isn\'t explicitly present in the M&L model, but is obviously needed. I assume its conc is fixed at 1uM for now, which is a bit high. PLA2 is stim 7x by PIP2 @ 0.5 uM (Leslie and Channon BBA 1045:261(1990) Leslie and Channon say PIP2 is present at 0.1 - 0.2mol% range in membs, which comes to 50 nM. Ref is Majerus et al Cell 37 pp 701-703 1984 Lets use a lower level of 30 nM, same ref....
constant: true
boundary condition: true
has only substance units: false
initial concentration: 2.5
initial amount: NaN
in compartment: 867160
type: Species

162624
stoichiometry: 1.0
species: 867839
type: SpeciesReference

162587
local parameters: 259093
notes: k3*PLA2_slash_DAG_minus_Ca_minus_PLA2_star__slash_kenz_slash_kenz_cplx
type: KineticLaw

868879
kinetic law: 161668
product: 161656
reactant: 161644
reactant: 161632
notes: The original kinetics have been modified to obey the k2 = 4 * k3 rule, while keeping kcat and Km fixed. As noted in the NOTES, the only constraining data point is the time course of MAPK dephosphorylation, which this model satisfies. It would be nice to have more accurate estimates of rate consts and MKP-1 levels from the literature. Effective Km : 67 nM kcat = 1.43 umol/min/mg
fast: false
reversible: true
type: Reaction

160880
local parameters: 258990
local parameters: 258989
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

159751
exponent: -1.0
scale: 0
multipler: 1.0
kind: SECOND
type: SBMLUnit

259071
units: 159763
value: 1.35E-12
type: LocalParameter

162538
local parameters: 259092
local parameters: 259089
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

258973
units: 159763
value: 6.0E-12
type: LocalParameter

869019
kinetic law: 162006
product: 161994
product: 161982
reactant: 161970
fast: false
reversible: false
type: Reaction

160467
stoichiometry: 1.0
species: 868019
type: SpeciesReference

259020
units: 159727
value: 4.2E-13
type: LocalParameter

867219
constant: false
boundary condition: false
has only substance units: false
initial concentration: 9.43516666666667E-21
initial amount: NaN
in compartment: 867160
type: Species

868839
kinetic law: 161570
product: 161558
reactant: 161546
reactant: 161534
notes: Km = 25uM @ 50 uM ATP and 1mg/ml MBP (huge XS of substrate) Vmax = 4124 pmol/min/ml at a conc of 125 pmol/ml of enz, so: k3 = .5/sec (rate limiting) k1 = (k2 + k3)/Km = (.5 + 0)/(25*6e5) = 2e-8 (#/cell)^-1 #s from Sanghera et al JBC 265 pp 52 , 1990. From Nemenoff et al JBC 268(3):1960-1964 - using Sanghera\'s 1e-4 ratio of MAPK to protein, we get k3 = 7/sec from 1000 pmol/min/mg fig 5
fast: false
reversible: true
type: Reaction

160783
local parameters: 258987
local parameters: 258986
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

868599
kinetic law: 160977
product: 160965
reactant: 160953
reactant: 160941
notes: Rate consts from PKC-act-raf. This reaction activates GEF. It can lead to at least 2X stim of ras, and a 2X stim of MAPK over and above that obtained via direct phosph of c-raf. Note that it is a push-pull reaction, and there is also a contribution through the phosphorylation and inactivation of GAPs. The original PKC-act-raf rate consts are too fast. We lower K1 by 10 X
fast: false
reversible: true
type: Reaction

161255
stoichiometry: 1.0
species: 867439
type: SpeciesReference

258960
units: 159727
value: 2.0E-12
type: LocalParameter

258974
units: 159727
value: 1.0E-13
type: LocalParameter

869059
kinetic law: 162103
product: 162091
product: 162079
reactant: 162067
fast: false
reversible: false
type: Reaction

162672
stoichiometry: 1.0
species: 867819
type: SpeciesReference

162490
local parameters: 259087
notes: k3*PLA2_slash_PIP2_minus_Ca_minus_PLA2_star__slash_kenz_slash_kenz_cplx
type: KineticLaw

868519
kinetic law: 160783
product: 160771
reactant: 160759
reactant: 160747
notes: Rate consts from Chen et al Biochem 32, 1032 (1993) k3 = k2 = 4 k1 = 9e-5 recalculated gives 1.666e-5, which is not very different. Looks like k3 is rate-limiting in this case: there is a huge amount of craf locked up in the enz complex. Let us assume a 10x higher Km, ie, lower affinity. k1 drops by 10x. Also changed k2 to 4x k3. Lowerd k1 to 1e-6 to balance 10X DAG sensitivity of PKC
fast: false
reversible: true
type: Reaction

161534
stoichiometry: 1.0
species: 867659
type: SpeciesReference

868259
kinetic law: 160212
product: 160199
reactant: 160187
reactant: 160175
notes: kf raised 10 X based on Shinomura et al PNAS 88 5149-5153 1991 closer analysis of Shinomura et al: kf now 1e-8 (was 1.66e-8). Further tweak. To get sufficient AA synergy, increase kf to 1.5e-8 26 June 1996: Corrected DAG levels: reduce kf by 15x from 1.5e-8 to 1e-9
fast: false
reversible: true
type: Reaction

160904
stoichiometry: 1.0
species: 867979
type: SpeciesReference

161390
stoichiometry: 1.0
species: 867459
type: SpeciesReference

162526
stoichiometry: 1.0
species: 867799
type: SpeciesReference

258961
units: 159763
value: 2.4E-11
type: LocalParameter

868539
kinetic law: 160831
product: 160819
product: 160807
reactant: 160795
fast: false
reversible: false
type: Reaction

162599
stoichiometry: 1.0
species: 868059
type: SpeciesReference

867279
constant: false
boundary condition: false
has only substance units: false
initial concentration: 2.51883333333333E-19
initial amount: NaN
in compartment: 867160
type: Species

258971
units: 159727
value: 4.0E-13
type: LocalParameter

161267
stoichiometry: 1.0
species: 867440
type: SpeciesReference

160309
local parameters: 258962
local parameters: 258961
notes: kf*MAPK_slash_craf_minus_1_star_*Ras_slash_GTP_minus_Ras-kb*MAPK_slash_Raf_minus_GTP_minus_Ras_star_
type: KineticLaw

259105
units: 159727
value: 2.0E-14
type: LocalParameter

868239
kinetic law: 160162
product: 160149
reactant: 160137
reactant: 160125
notes: Raise kf from 1.667e-10 to 2e-10 to get better match to data.
fast: false
reversible: true
type: Reaction

160795
stoichiometry: 1.0
species: 867300
type: SpeciesReference

162611
stoichiometry: 1.0
species: 867819
type: SpeciesReference

868279
kinetic law: 160261
product: 160248
reactant: 160236
reactant: 160224
notes: Reduced kf to 0.66X to match Shinomura et al data. Initial: kf = 3.3333e-9 New: 2e-9 Newer: 2e-8 kb was 0.2 now 2.
fast: false
reversible: true
type: Reaction

259032
units: 159727
value: 8.0E-11
type: LocalParameter

160455
local parameters: 258968
local parameters: 258967
notes: kf*temp_minus_PIP2*PLA2_slash_PLA2_minus_Ca_star_-kb*PLA2_slash_PIP2_minus_Ca_minus_PLA2_star_
type: KineticLaw

162283
stoichiometry: 1.0
species: 867660
type: SpeciesReference

162805
stoichiometry: 1.0
species: 867999
type: SpeciesReference

160041
local parameters: 258948
local parameters: 258947
notes: kf*PKC_slash_PKC_minus_Ca*AA-kb*PKC_slash_PKC_minus_Ca_minus_AA_star_
type: KineticLaw

258962
units: 159727
value: 5.0E-13
type: LocalParameter

867299
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 867160
type: Species

258972
units: 159727
value: 0.0
type: LocalParameter

868219
kinetic law: 160077
product: 160065
reactant: 160053
notes: Assume slowish too. Schaechter and Benowitz
fast: false
reversible: true
type: Reaction

867819
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 867160
type: Species

867419
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 867160
type: Species

869279
kinetic law: 162636
product: 162624
reactant: 162611
reactant: 162599
notes: This form should be 3 to 6 times as fast as the Ca-only form. I have scaled by 4x which seems to give a 5x rise. 10x raise Oct 22 12 x oct 24, changed k2 = 4 * k3
fast: false
reversible: true
type: Reaction

258984
units: 159727
value: 1.0E-13
type: LocalParameter

160053
stoichiometry: 1.0
species: 867279
type: SpeciesReference

162562
stoichiometry: 1.0
species: 867299
type: SpeciesReference

160113
local parameters: 258952
local parameters: 258951
notes: kf*PKC_slash_PKC_minus_cytosolic-kb*PKC_slash_PKC_minus_basal_star_
type: KineticLaw

162685
local parameters: 259099
notes: k3*PLA2_slash_PLA2_star__minus_Ca_slash_kenz_slash_kenz_cplx
type: KineticLaw

162817
stoichiometry: 1.0
species: 868001
type: SpeciesReference

162018
stoichiometry: 1.0
species: 867420
type: SpeciesReference

162211
stoichiometry: 1.0
species: 868059
type: SpeciesReference

259014
units: 159727
value: 4.2E-13
type: LocalParameter

867359
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.18
initial amount: NaN
in compartment: 867160
type: Species

161970
stoichiometry: 1.0
species: 867599
type: SpeciesReference

162271
stoichiometry: 1.0
species: 867299
type: SpeciesReference

162187
stoichiometry: 1.0
species: 867559
type: SpeciesReference

259033
units: 159727
value: 2.0E-11
type: LocalParameter

867439
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 867160
type: Species

869299
kinetic law: 162685
product: 162672
product: 162660
reactant: 162648
fast: false
reversible: false
type: Reaction

161231
local parameters: 259009
notes: k3*MAPK_slash_MAPKK_star__slash_MAPKKthr_slash_MAPKKthr_cplx
type: KineticLaw

159835
stoichiometry: 1.0
species: 867280
type: SpeciesReference

258983
units: 159727
value: 0.0
type: LocalParameter

162648
stoichiometry: 1.0
species: 867839
type: SpeciesReference

868659
kinetic law: 161134
product: 161121
product: 161108
reactant: 161095
fast: false
reversible: false
type: Reaction

259081
units: 159727
value: 1.104E-11
type: LocalParameter

161055
stoichiometry: 1.0
species: 867399
type: SpeciesReference

160358
local parameters: 258964
local parameters: 258963
notes: kf*PLA2_slash_PLA2_minus_cytosolic*Ca-kb*PLA2_slash_PLA2_minus_Ca_star_
type: KineticLaw

259035
units: 159763
value: 7.5E-11
type: LocalParameter

259095
units: 159763
value: 3.0E-11
type: LocalParameter

868180
kinetic law: 159993
product: 159981
reactant: 159969
notes: Raise kb from .087 to 0.1 to match data from Shinomura et al. Lower kf from 1.155 to 1.0 to match data from Shinomura et al.
fast: false
reversible: true
type: Reaction

867979
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 867160
type: Species

867340
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 867160
type: Species

258997
units: 159727
value: 4.0E-12
type: LocalParameter

161146
stoichiometry: 1.0
species: 867380
type: SpeciesReference

160977
local parameters: 258996
local parameters: 258993
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

259015
units: 159727
value: 1.05E-13
type: LocalParameter

869319
kinetic law: 162733
product: 162721
reactant: 162709
reactant: 162697
notes: Kinetics same as GEF-bg-act-ras
fast: false
reversible: true
type: Reaction

259005
units: 159763
value: 1.62E-11
type: LocalParameter

868139
kinetic law: 159872
product: 159860
reactant: 159848
reactant: 159835
notes: Need est of rate of assoc of Ca and PKC. Assume it is fast The original parameter-searched kf of 439.4 has been scaled by 1/6e8 to account for change of units to n. Kf now 8.16e-7, kb=.6085 Raised kf to 1e-6 to match Ca curve, kb to .5
fast: false
reversible: true
type: Reaction

162067
stoichiometry: 1.0
species: 867619
type: SpeciesReference

161885
stoichiometry: 1.0
species: 867339
type: SpeciesReference

162829
local parameters: 259110
local parameters: 259107
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

867440
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 867160
type: Species

162223
stoichiometry: 1.0
species: 867660
type: SpeciesReference

258986
units: 159763
value: 3.0E-13
type: LocalParameter

258996
units: 159727
value: 1.6E-11
type: LocalParameter

160065
stoichiometry: 1.0
species: 867180
type: SpeciesReference

160101
stoichiometry: 1.0
species: 867220
type: SpeciesReference

161068
stoichiometry: 1.0
species: 867400
type: SpeciesReference

162175
stoichiometry: 1.0
species: 867340
type: SpeciesReference

161243
stoichiometry: 1.0
species: 867359
type: SpeciesReference

868719
kinetic law: 161279
product: 161267
reactant: 161255
reactant: 161243
notes: Kinetics are the same as for the craf-1* activity, ie., k1=1.1e-6, k2=.42, k3 =0.105 These are based on Force et al PNAS USA 91 1270-1274 1994. These parms cannot reach the observed 4X stim of MAPK. So lets increase the affinity, ie, raise k1 10X to 1.1e-5 Lets take it back down to where it was. Back up to 5X: 5.5e-6
fast: false
reversible: true
type: Reaction

259002
units: 159727
value: 6.0E-13
type: LocalParameter

258937
units: 159763
value: 6.0E-13
type: LocalParameter

259021
units: 159727
value: 1.05E-13
type: LocalParameter

259023
units: 159763
value: 1.95E-12
type: LocalParameter

259083
units: 159763
value: 9.0E-12
type: LocalParameter

161194
stoichiometry: 1.0
species: 867419
type: SpeciesReference

867142
constant: true
size: 1.0E-18
spatial dimensions: 3.0
type: Compartment

160990
stoichiometry: 1.0
species: 867320
type: SpeciesReference

868759
kinetic law: 161378
product: 161365
reactant: 161352
reactant: 161339
notes: Same kinetics as other c-raf activated forms. See Force et al PNAS 91 1270-1274 1994. k1 = 1.1e-6, k2 = .42, k3 = 1.05 raise k1 to 5.5e-6
fast: false
reversible: true
type: Reaction

258985
units: 159727
value: 0.0
type: LocalParameter

162636
local parameters: 259098
local parameters: 259095
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

159823
exponent: 1.0
scale: -6
multipler: 1.0
kind: MOLE
type: SBMLUnit

259093
units: 159727
value: 6.0E-11
type: LocalParameter

162575
stoichiometry: 1.0
species: 867779
type: SpeciesReference

868739
kinetic law: 161327
product: 161315
product: 161303
reactant: 161291
fast: false
reversible: false
type: Reaction

160346
stoichiometry: 1.0
species: 867660
type: SpeciesReference

259017
units: 159763
value: 3.3E-12
type: LocalParameter

161873
stoichiometry: 1.0
species: 867579
type: SpeciesReference

162079
stoichiometry: 1.0
species: 867359
type: SpeciesReference

867480
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 867160
type: Species

259003
units: 159727
value: 1.5E-13
type: LocalParameter

161158
stoichiometry: 1.0
species: 867399
type: SpeciesReference

160965
stoichiometry: 1.0
species: 867320
type: SpeciesReference

162308
stoichiometry: 1.0
species: 868059
type: SpeciesReference

259092
units: 159727
value: 2.4E-10
type: LocalParameter

868099
constant: false
boundary condition: true
has only substance units: false
initial concentration: 2.12216666666667E-16
initial amount: NaN
in compartment: 867160
type: Species

161994
stoichiometry: 1.0
species: 867559
type: SpeciesReference

259038
units: 159727
value: 4.0E-12
type: LocalParameter

162163
stoichiometry: 1.0
species: 867639
type: SpeciesReference

160868
stoichiometry: 1.0
species: 867319
type: SpeciesReference

258980
units: 159727
value: 1.0E-12
type: LocalParameter

160077
local parameters: 258950
local parameters: 258949
notes: kf*PKC_slash_PKC_minus_DAG_minus_AA-kb*PKC_slash_PKC_minus_DAG_minus_AA_star_
type: KineticLaw

160137
stoichiometry: 1.0
species: 867280
type: SpeciesReference

161849
stoichiometry: 1.0
species: 867579
type: SpeciesReference

159957
local parameters: 258944
local parameters: 258943
notes: kf*PKC_slash_PKC_minus_Ca-kb*PKC_slash_PKC_minus_Ca_minus_memb_star_
type: KineticLaw

160017
stoichiometry: 1.0
species: 867299
type: SpeciesReference

160953
stoichiometry: 1.0
species: 868099
type: SpeciesReference

867759
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 867160
type: Species

258993
units: 159763
value: 6.0E-12
type: LocalParameter

160261
local parameters: 258960
local parameters: 258959
notes: kf*PKC_slash_PKC_minus_DAG*AA-kb*PKC_slash_PKC_minus_DAG_minus_AA
type: KineticLaw

259039
units: 159727
value: 1.0E-12
type: LocalParameter

160334
stoichiometry: 1.0
species: 868039
type: SpeciesReference

259029
units: 159763
value: 3.9E-12
type: LocalParameter

868859
kinetic law: 161620
product: 161608
product: 161596
reactant: 161583
fast: false
reversible: false
type: Reaction

868779
kinetic law: 161426
product: 161414
product: 161402
reactant: 161390
fast: false
reversible: false
type: Reaction

160212
local parameters: 258958
local parameters: 258955
notes: kf*PKC_slash_PKC_minus_cytosolic*DAG-kb*PKC_slash_PKC_minus_DAG
type: KineticLaw

868799
kinetic law: 161474
product: 161462
reactant: 161450
reactant: 161438
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

868059
notes: arachodonylphosphatidylcholine is the favoured substrate from Wijkander and Sundler, JBC 202 pp 873-880, 1991. Their assay used 30 uM substrate, which is what the kinetics in this model are based on. For the later model we should locate a more realistic value for APC.
constant: true
boundary condition: true
has only substance units: false
initial concentration: 30.0
initial amount: NaN
in compartment: 867160
type: Species

161656
stoichiometry: 1.0
species: 867519
type: SpeciesReference

869079
kinetic law: 162151
product: 162139
reactant: 162127
reactant: 162115
notes: Ueki et al JBC 269(22) pp 15756-15761 1994 show hyperphosphorylation of craf, so this is there to dephosphorylate it. Identity of phosphatase is not known to me, but it may be PP2A like the rest, so I have made it so.
fast: false
reversible: true
type: Reaction

867779
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 867160
type: Species

869139
kinetic law: 162296
product: 162283
product: 162271
reactant: 162259
fast: false
reversible: false
type: Reaction

161182
local parameters: 259008
local parameters: 259005
notes: k1*MAPK_slash_MAPK_minus_tyr*MAPK_slash_MAPKK_star_-k2*MAPK_slash_MAPKK_star__slash_MAPKKthr_slash_MAPKKthr_cplx
type: KineticLaw

259011
units: 159763
value: 3.3E-12
type: LocalParameter

161121
stoichiometry: 1.0
species: 867399
type: SpeciesReference

160856
stoichiometry: 1.0
species: 868099
type: SpeciesReference

867479
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 867160
type: Species

259080
units: 159727
value: 4.416E-11
type: LocalParameter

258982
units: 159727
value: 1.0E-16
type: LocalParameter

259026
units: 159727
value: 4.0E-11
type: LocalParameter

160661
local parameters: 258981
local parameters: 258980
notes: kf*Ras_slash_GEF_star_-kb*Ras_slash_inact_minus_GEF
type: KineticLaw

161982
stoichiometry: 1.0
species: 867420
type: SpeciesReference

868439
kinetic law: 160624
product: 160612
reactant: 160600
fast: false
reversible: true
type: Reaction

868459
kinetic law: 160661
product: 160648
reactant: 160636
fast: false
reversible: true
type: Reaction

159969
stoichiometry: 1.0
species: 867240
type: SpeciesReference

161837
stoichiometry: 1.0
species: 867559
type: SpeciesReference

162697
stoichiometry: 1.0
species: 867959
type: SpeciesReference

160089
stoichiometry: 1.0
species: 867280
type: SpeciesReference

162550
stoichiometry: 1.0
species: 867799
type: SpeciesReference

160125
stoichiometry: 1.0
species: 867299
type: SpeciesReference

867459
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 867160
type: Species

159909
stoichiometry: 1.0
species: 867240
type: SpeciesReference

160322
stoichiometry: 1.0
species: 867659
type: SpeciesReference

868220
kinetic law: 160113
product: 160101
reactant: 160089
notes: Initial basal levels were set by kf = 1, kb = 20. In model, though, the basal levels of PKC activity are higher.
fast: false
reversible: true
type: Reaction

258991
units: 159727
value: 4.0E-12
type: LocalParameter

161897
stoichiometry: 1.0
species: 867559
type: SpeciesReference

160029
stoichiometry: 1.0
species: 867199
type: SpeciesReference

160941
stoichiometry: 1.0
species: 867879
type: SpeciesReference

258981
units: 159727
value: 0.0
type: LocalParameter

867499
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0032
initial amount: NaN
in compartment: 867160
type: Species

259027
units: 159727
value: 1.0E-11
type: LocalParameter

161134
local parameters: 259003
notes: k3*MAPK_slash_MAPKK_star__slash_MAPKKtyr_slash_MAPKKtyr_cplx
type: KineticLaw

161170
stoichiometry: 1.0
species: 867419
type: SpeciesReference

160224
stoichiometry: 1.0
species: 867260
type: SpeciesReference

161668
local parameters: 259038
local parameters: 259035
notes: k1*MAPK_slash_MAPK_minus_tyr*MKP_minus_1-k2*MKP_minus_1_slash_MKP1_minus_tyr_minus_deph_slash_MKP1_minus_tyr_minus_deph_cplx
type: KineticLaw

867579
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 867160
type: Species

161753
stoichiometry: 1.0
species: 867539
type: SpeciesReference

160759
stoichiometry: 1.0
species: 868099
type: SpeciesReference

867659
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.4
initial amount: NaN
in compartment: 867160
type: Species

160005
stoichiometry: 1.0
species: 867179
type: SpeciesReference

868679
kinetic law: 161182
product: 161170
reactant: 161158
reactant: 161146
notes: Rate consts same as for MAPKKtyr.
fast: false
reversible: true
type: Reaction

161596
stoichiometry: 1.0
species: 867859
type: SpeciesReference

162866
stoichiometry: 1.0
species: 867999
type: SpeciesReference

160273
stoichiometry: 1.0
species: 867340
type: SpeciesReference

867599
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 867160
type: Species

159993
local parameters: 258946
local parameters: 258945
notes: kf*PKC_slash_PKC_minus_Ca_minus_DAG-kb*PKC_slash_PKC_minus_DAG_minus_memb_star_
type: KineticLaw

162430
stoichiometry: 1.0
species: 867759
type: SpeciesReference

162370
stoichiometry: 1.0
species: 867299
type: SpeciesReference

161692
stoichiometry: 1.0
species: 867360
type: SpeciesReference

161813
local parameters: 259045
notes: k3*MKP_minus_1_slash_MKP1_minus_thr_minus_deph_slash_MKP1_minus_thr_minus_deph_cplx
type: KineticLaw

161365
stoichiometry: 1.0
species: 867459
type: SpeciesReference

869379
kinetic law: 162878
product: 162866
product: 162854
reactant: 162841
fast: false
reversible: false
type: Reaction

160819
stoichiometry: 1.0
species: 868099
type: SpeciesReference

162042
stoichiometry: 1.0
species: 867619
type: SpeciesReference

160370
stoichiometry: 1.0
species: 868079
type: SpeciesReference

869179
kinetic law: 162394
product: 162382
product: 162370
reactant: 162358
fast: false
reversible: false
type: Reaction

162345
local parameters: 259080
local parameters: 259077
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

160149
stoichiometry: 1.0
species: 867239
type: SpeciesReference

159921
local parameters: 258942
local parameters: 258941
notes: kf*DAG*PKC_slash_PKC_minus_Ca-kb*PKC_slash_PKC_minus_Ca_minus_DAG
type: KineticLaw

869159
kinetic law: 162345
product: 162332
reactant: 162320
reactant: 162308
notes: 10 X raise oct 22 12 X further raise oct 24 to allow for correct conc of enzyme
fast: false
reversible: true
type: Reaction

162247
local parameters: 259074
local parameters: 259071
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

867859
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 867160
type: Species

MODEL9071122126
reaction: 868739
reaction: 869039
reaction: 868679
species: 868001
species: 867879
species: 867839
reaction: 868459
species: 867499
reaction: 868219
reaction: 869359
reaction: 869119
reaction: 868939
species: 867559
species: 867179
volume units: 679943
species: 867519
reaction: 868199
reaction: 868719
is described by: http://identifiers.org/pubmed/9888852
reaction: 869099
reaction: 868899
reaction: 868659
species: 867660
species: 867399
species: 867320
reaction: 868439
reaction: 868279
species: 867199
species: 867579
reaction: 869339
species: 867279
species: 867779
species: 867739
species: 867439
species: 867380
species: 867340
reaction: 868179
species: 867180
reaction: 868879
reaction: 869079
reaction: 868639
rule: 868119
reaction: 868499
reaction: 868419
notes: This model is based closely on the one from Bhalla US and Iyengar R. Science (1999) 283(5400):381-7. This is a stripped down version with only the essential components of the feedback loop:PKC, Ras and the MAPK cascade, and PLA2 in the synapse. The upregulation of MKP-1 is not incorporated in this model since it is treated as a fixed regulatory input. This model was used to develop figures 2 - 4 which show the bistable region of parameter space when the regulatory inputs Ca, PP2A and MKP-1 are varied. This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2011 The BioModels.net Team. To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information. In summary, you are entitled to use this encoded model in absolutely any manner you deem suitable, verbatim, or with modification, alone or embedded it in a larger context, redistribute it, commercially or not, in a restricted way or not.. To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.
species: 867799
species: 867459
species: 867419
reaction: 869319
species: 867979
species: 867939
reaction: 868159
species: 868019
species: 867219
species: 867400
reaction: 869299
reaction: 869059
reaction: 868859
reaction: 868619
reaction: 868180
area units: area
species: 867999
species: 867959
species: 867480
reaction: 868599
reaction: 869379
species: 867539
species: 868079
reaction: 868379
species: 867239
reaction: 868139
time units: 131570
species: 867300
species: 867359
reaction: 869279
reaction: 868839
name: Bhalla1999_3d_fold_model
species: 868099
length unit: length
reaction: 868579

162854
stoichiometry: 1.0
species: 867959
type: SpeciesReference

868359
kinetic law: 160455
product: 160443
reactant: 160431
reactant: 160419
fast: false
reversible: true
type: Reaction

160747
stoichiometry: 1.0
species: 867339
type: SpeciesReference

161741
stoichiometry: 1.0
species: 867499
type: SpeciesReference

867400
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 867160
type: Species

162382
stoichiometry: 1.0
species: 867699
type: SpeciesReference

162442
local parameters: 259086
local parameters: 259083
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

160285
stoichiometry: 1.0
species: 867939
type: SpeciesReference

161042
stoichiometry: 1.0
species: 867360
type: SpeciesReference

160807
stoichiometry: 1.0
species: 867340
type: SpeciesReference

161438
stoichiometry: 1.0
species: 867340
type: SpeciesReference

161825
stoichiometry: 1.0
species: 867340
type: SpeciesReference

868019
notes: Baseline is 11.661 from running combined model to steady state. See ALL/NOTES for 23 Apr 1998.
constant: true
boundary condition: true
has only substance units: false
initial concentration: 11.661
initial amount: NaN
in compartment: 867160
type: Species

162769
stoichiometry: 1.0
species: 867899
type: SpeciesReference

868979
kinetic law: 161909
product: 161897
product: 161885
reactant: 161873
fast: false
reversible: false
type: Reaction

161081
local parameters: 259002
local parameters: 258999
notes: k1*MAPK_slash_MAPK*MAPK_slash_MAPKK_star_-k2*MAPK_slash_MAPKK_star__slash_MAPKKtyr_slash_MAPKKtyr_cplx
type: KineticLaw

162235
stoichiometry: 1.0
species: 867679
type: SpeciesReference

161729
stoichiometry: 1.0
species: 867460
type: SpeciesReference

160297
stoichiometry: 1.0
species: 867439
type: SpeciesReference

258948
units: 159727
value: 1.0E-13
type: LocalParameter

162320
stoichiometry: 1.0
species: 867699
type: SpeciesReference

161777
stoichiometry: 1.0
species: 867539
type: SpeciesReference

162394
local parameters: 259081
notes: k3*PLA2_slash_PIP2_minus_PLA2_star__slash_kenz_slash_kenz_cplx
type: KineticLaw

259047
units: 159763
value: 1.98E-12
type: LocalParameter

160406
local parameters: 258966
local parameters: 258965
notes: kf*temp_minus_PIP2*PLA2_slash_PLA2_minus_cytosolic-kb*PLA2_slash_PIP2_minus_PLA2_star_
type: KineticLaw

869219
kinetic law: 162490
product: 162478
product: 162466
reactant: 162454
fast: false
reversible: false
type: Reaction

259099
units: 159727
value: 1.2E-10
type: LocalParameter

258987
units: 159727
value: 1.6E-11
type: LocalParameter

160735
local parameters: 258985
local parameters: 258984
notes: kf*Ras_slash_GAP_star_-kb*Ras_slash_GAP
type: KineticLaw

160431
stoichiometry: 1.0
species: 867660
type: SpeciesReference

160199
stoichiometry: 1.0
species: 867260
type: SpeciesReference

159945
stoichiometry: 1.0
species: 867200
type: SpeciesReference

258947
units: 159763
value: 1.2E-15
type: LocalParameter

161717
local parameters: 259039
notes: k3*MKP_minus_1_slash_MKP1_minus_tyr_minus_deph_slash_MKP1_minus_tyr_minus_deph_cplx
type: KineticLaw

867239
constant: false
boundary condition: false
has only substance units: false
initial concentration: 1.81333333333333E-17
initial amount: NaN
in compartment: 867160
type: Species

159739
exponent: 1.0
scale: 0
multipler: 1.0
kind: LITRE
type: SBMLUnit

161789
stoichiometry: 1.0
species: 867380
type: SpeciesReference

162709
stoichiometry: 1.0
species: 867899
type: SpeciesReference

258988
units: 159727
value: 4.0E-12
type: LocalParameter

160394
stoichiometry: 1.0
species: 867699
type: SpeciesReference

867420
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 867160
type: Species

259086
units: 159727
value: 1.44E-10
type: LocalParameter

867160
constant: true
size: 1.0E-12
spatial dimensions: 3.0
type: Compartment

259009
units: 159727
value: 1.5E-13
type: LocalParameter

868579
kinetic law: 160929
product: 160917
product: 160904
reactant: 160892
fast: false
reversible: false
type: Reaction

162878
local parameters: 259111
notes: k3*Ras_slash_GAP_slash_GAP_minus_inact_minus_ras_slash_GAP_minus_inact_minus_ras_cplx
type: KineticLaw

162332
stoichiometry: 1.0
species: 867719
type: SpeciesReference

867559
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.224
initial amount: NaN
in compartment: 867160
type: Species

869359
kinetic law: 162829
product: 162817
reactant: 162805
reactant: 162793
notes: From Eccleston et al JBC 268(36)pp27012-19 get Kd < 2uM, kcat - 10/sec From Martin et al Cell 63 843-849 1990 get Kd ~ 250 nM, kcat = 20/min I will go with the Eccleston figures as there are good error bars (10%). In general the values are reasonably close. k1 = 1.666e-3/sec, k2 = 1000/sec, k3 = 10/sec (note k3 is rate-limiting)
fast: false
reversible: true
type: Reaction

161704
stoichiometry: 1.0
species: 867499
type: SpeciesReference

258989
units: 159763
value: 6.0E-12
type: LocalParameter

868001
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 867160
type: Species

160187
stoichiometry: 1.0
species: 868019
type: SpeciesReference

867539
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 867160
type: Species

868639
kinetic law: 161081
product: 161068
reactant: 161055
reactant: 161042
notes: The actual MAPKK is 2 forms from Seger et al JBC 267:20 14373(1992) Vmax = 150nmol/min/mg From Haystead et al FEBS 306(1):17-22 we get Km=46.6nM for at least one of the phosphs. Putting these together: k3=0.15/sec, scale to get k2=0.6. k1=0.75/46.6nM=2.7e-5
fast: false
reversible: true
type: Reaction

259087
units: 159727
value: 3.6E-11
type: LocalParameter

259059
units: 159763
value: 1.98E-12
type: LocalParameter

868559
kinetic law: 160880
product: 160868
reactant: 160856
reactant: 160844
notes: Rate consts copied from PCK-act-raf This reaction inactivates GAP. The idea is from the Boguski and McCormick review.
fast: false
reversible: true
type: Reaction

258999
units: 159763
value: 1.62E-11
type: LocalParameter

160723
stoichiometry: 1.0
species: 867999
type: SpeciesReference

161765
local parameters: 259044
local parameters: 259041
notes: k1*MAPK_star_*MKP_minus_1-k2*MKP_minus_1_slash_MKP1_minus_thr_minus_deph_slash_MKP1_minus_thr_minus_deph_cplx
type: KineticLaw

160443
stoichiometry: 1.0
species: 867739
type: SpeciesReference

161352
stoichiometry: 1.0
species: 867439
type: SpeciesReference

258949
units: 159727
value: 2.0E-12
type: LocalParameter

259089
units: 159763
value: 1.5E-11
type: LocalParameter

161108
stoichiometry: 1.0
species: 867380
type: SpeciesReference

159933
stoichiometry: 1.0
species: 867179
type: SpeciesReference

867180
constant: false
boundary condition: false
has only substance units: false
initial concentration: 4.91366666666667E-18
initial amount: NaN
in compartment: 867160
type: Species

258959
units: 159763
value: 1.8E-14
type: LocalParameter

162259
stoichiometry: 1.0
species: 867679
type: SpeciesReference

259008
units: 159727
value: 6.0E-13
type: LocalParameter

868039
constant: true
boundary condition: true
has only substance units: false
initial concentration: 0.08
initial amount: NaN
in compartment: 867160
type: Species

867519
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 867160
type: Species

160382
stoichiometry: 1.0
species: 867659
type: SpeciesReference

162030
stoichiometry: 1.0
species: 867559
type: SpeciesReference

259098
units: 159727
value: 4.8E-10
type: LocalParameter

161801
stoichiometry: 1.0
species: 867499
type: SpeciesReference

867639
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 867160
type: Species

160710
stoichiometry: 1.0
species: 867979
type: SpeciesReference

867319
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 867160
type: Species

259110
units: 159727
value: 1.0E-9
type: LocalParameter

259057
units: 159727
value: 6.0E-12
type: LocalParameter

162660
stoichiometry: 1.0
species: 867299
type: SpeciesReference

162733
local parameters: 259104
local parameters: 259101
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

259062
units: 159727
value: 2.5E-11
type: LocalParameter

160540
local parameters: 258972
local parameters: 258971
notes: kf*AA-kb*PLA2_slash_APC
type: KineticLaw

867839
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 867160
type: Species

258964
units: 159727
value: 1.0E-13
type: LocalParameter

161003
stoichiometry: 1.0
species: 867899
type: SpeciesReference

160515
stoichiometry: 1.0
species: 867299
type: SpeciesReference

161620
local parameters: 259033
notes: k3*MAPK_star__slash_MAPK_star__slash_MAPK_star__cplx
type: KineticLaw

159860
stoichiometry: 1.0
species: 867179
type: SpeciesReference

258958
units: 159727
value: 1.0E-13
type: LocalParameter

258944
units: 159727
value: 3.5026E-12
type: LocalParameter

161402
stoichiometry: 1.0
species: 867399
type: SpeciesReference

259111
units: 159727
value: 1.0E-11
type: LocalParameter

162115
stoichiometry: 1.0
species: 867379
type: SpeciesReference

160892
stoichiometry: 1.0
species: 867319
type: SpeciesReference

259075
units: 159727
value: 5.4E-12
type: LocalParameter

159787
exponent: -1.0
scale: -6
multipler: 1.0
kind: MOLE
type: SBMLUnit

259056
units: 159727
value: 2.5E-11
type: LocalParameter

161498
stoichiometry: 1.0
species: 867379
type: SpeciesReference

258963
units: 159763
value: 1.00002E-12
type: LocalParameter

160175
stoichiometry: 1.0
species: 867280
type: SpeciesReference

867280
constant: false
boundary condition: false
has only substance units: false
initial concentration: 1.0
initial amount: NaN
in compartment: 867160
type: Species

867879
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.1
initial amount: NaN
in compartment: 867160
type: Species

259041
units: 159763
value: 7.5E-11
type: LocalParameter

868699
kinetic law: 161231
product: 161219
product: 161207
reactant: 161194
fast: false
reversible: false
type: Reaction

161219
stoichiometry: 1.0
species: 867399
type: SpeciesReference

161303
stoichiometry: 1.0
species: 867420
type: SpeciesReference

162478
stoichiometry: 1.0
species: 867739
type: SpeciesReference

258943
units: 159727
value: 1.2705E-12
type: LocalParameter

161608
stoichiometry: 1.0
species: 867460
type: SpeciesReference

867679
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 867160
type: Species

868339
kinetic law: 160406
product: 160394
reactant: 160382
reactant: 160370
fast: false
reversible: true
type: Reaction

258966
units: 159727
value: 5.0E-13
type: LocalParameter

160552
stoichiometry: 1.0
species: 867859
type: SpeciesReference

259074
units: 159727
value: 2.16E-11
type: LocalParameter

160503
local parameters: 258970
local parameters: 258969
notes: kf*DAG*PLA2_slash_PLA2_minus_Ca_star_-kb*PLA2_slash_DAG_minus_Ca_minus_PLA2_star_
type: KineticLaw

258976
units: 159727
value: 1.7E-13
type: LocalParameter

160162
local parameters: 258954
local parameters: 258953
notes: kf*AA*PKC_slash_PKC_minus_cytosolic-kb*PKC_slash_PKC_minus_AA_star_
type: KineticLaw

161570
local parameters: 259032
local parameters: 259029
notes: k1*PLA2_slash_PLA2_minus_cytosolic*MAPK_star_-k2*MAPK_star__slash_MAPK_star__slash_MAPK_star__cplx
type: KineticLaw

161945
stoichiometry: 1.0
species: 867599
type: SpeciesReference

259045
units: 159727
value: 1.0E-12
type: LocalParameter

162721
stoichiometry: 1.0
species: 867919
type: SpeciesReference

868999
kinetic law: 161957
product: 161945
reactant: 161933
reactant: 161921
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

259044
units: 159727
value: 4.0E-12
type: LocalParameter

160600
stoichiometry: 1.0
species: 867859
type: SpeciesReference

159872
local parameters: 258940
local parameters: 258937
notes: kf*PKC_slash_PKC_minus_cytosolic*Ca-kb*PKC_slash_PKC_minus_Ca
type: KineticLaw

258946
units: 159727
value: 1.0E-13
type: LocalParameter

869239
kinetic law: 162538
product: 162526
reactant: 162514
reactant: 162502
notes: 10 X raise oct 22 12 X raise oct 24 + conversion to k2 =4 * k3
fast: false
reversible: true
type: Reaction

258965
units: 159763
value: 1.2E-15
type: LocalParameter

868919
kinetic law: 161765
product: 161753
reactant: 161741
reactant: 161729
notes: See MKP1-tyr-deph
fast: false
reversible: true
type: Reaction

259063
units: 159727
value: 6.0E-12
type: LocalParameter

159775
exponent: 2.0
scale: 0
multipler: 1.0
kind: LITRE
type: SBMLUnit

160491
stoichiometry: 1.0
species: 867779
type: SpeciesReference

161315
stoichiometry: 1.0
species: 867439
type: SpeciesReference

868959
kinetic law: 161861
product: 161849
reactant: 161837
reactant: 161825
notes: See parent PPhosphatase2A for parms
fast: false
reversible: true
type: Reaction

868379
kinetic law: 160503
product: 160491
reactant: 160479
reactant: 160467
notes: 27 June 1996 Scaled kf down by 0.015 from 3.33e-7 to 5e-9 to fit with revised DAG estimates and use of mole-fraction to calculate eff on PLA2.
fast: false
reversible: true
type: Reaction

258955
units: 159763
value: 6.0E-16
type: LocalParameter

868299
kinetic law: 160309
product: 160297
reactant: 160285
reactant: 160273
notes: Assume the binding is fast and is limited only by the amount of Ras* available. So kf = kb/[craf-1] If kb is 1/sec, then kf = 1/0.2 uM = 1/(0.2 * 6e5) = 8.3e-6 Later: Raise it by 10 X to 4e-5 From Hallberg et al JBC 269:6 3913-3916 1994, 3% of cellular Raf is complexed with Ras. So we raise kb 4 x to 4 This step needed to memb-anchor and activate Raf: Leevers et al Nature 369 411-414
fast: false
reversible: true
type: Reaction

869259
kinetic law: 162587
product: 162575
product: 162562
reactant: 162550
fast: false
reversible: false
type: Reaction

258945
units: 159727
value: 1.0E-12
type: LocalParameter

867380
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 867160
type: Species

867939
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 867160
type: Species

259053
units: 159763
value: 1.98E-12
type: LocalParameter

162406
stoichiometry: 1.0
species: 868059
type: SpeciesReference

259101
units: 159763
value: 1.98E-13
type: LocalParameter

160419
stoichiometry: 1.0
species: 868079
type: SpeciesReference

159884
stoichiometry: 1.0
species: 868019
type: SpeciesReference

162358
stoichiometry: 1.0
species: 867719
type: SpeciesReference

867200
constant: false
boundary condition: false
has only substance units: false
initial concentration: 1.3896E-17
initial amount: NaN
in compartment: 867160
type: Species

162757
stoichiometry: 1.0
species: 867939
type: SpeciesReference

258968
units: 159727
value: 1.0E-13
type: LocalParameter

162139
stoichiometry: 1.0
species: 867639
type: SpeciesReference

160612
stoichiometry: 1.0
species: 867659
type: SpeciesReference

867399
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 867160
type: Species

161426
local parameters: 259021
notes: k3*MAPK_slash_Raf_minus_GTP_minus_Ras_star__slash_Raf_minus_GTP_minus_Ras_star__dot_2_slash_Raf_minus_GTP_minus_Ras_star__dot_2_cplx
type: KineticLaw

161378
local parameters: 259020
local parameters: 259017
notes: k1*MAPK_slash_MAPKK_minus_ser*MAPK_slash_Raf_minus_GTP_minus_Ras_star_-k2*MAPK_slash_Raf_minus_GTP_minus_Ras_star__slash_Raf_minus_GTP_minus_Ras_star__dot_2_slash_Raf_minus_GTP_minus_Ras_star__dot_2_cplx
type: KineticLaw

161933
stoichiometry: 1.0
species: 867559
type: SpeciesReference

867199
constant: false
boundary condition: false
has only substance units: false
initial concentration: 1.75E-16
initial amount: NaN
in compartment: 867160
type: Species

868399
kinetic law: 160540
product: 160527
reactant: 160515
notes: I need to check if the AA degradation pathway really leads back to APC. Anyway, it is a convenient buffered pool to dump it back into. For the purposes of the full model we use a rate of degradation of 0.2/sec Raised decay to 0.4 : see PLA35.g notes for Feb17
fast: false
reversible: true
type: Reaction

258940
units: 159727
value: 5.0E-13
type: LocalParameter

868499
kinetic law: 160735
product: 160723
reactant: 160710
notes: Assume a reasonably good rate for dephosphorylating it, 1/sec
fast: false
reversible: true
type: Reaction

161644
stoichiometry: 1.0
species: 867499
type: SpeciesReference

258954
units: 159727
value: 1.0E-13
type: LocalParameter

160564
stoichiometry: 1.0
species: 868039
type: SpeciesReference

259065
units: 159763
value: 1.98E-12
type: LocalParameter

258967
units: 159763
value: 1.2E-14
type: LocalParameter

162454
stoichiometry: 1.0
species: 867759
type: SpeciesReference

867220
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.02
initial amount: NaN
in compartment: 867160
type: Species

867240
constant: false
boundary condition: false
has only substance units: false
initial concentration: 8.46316666666667E-23
initial amount: NaN
in compartment: 867160
type: Species

258953
units: 159763
value: 1.2E-16
type: LocalParameter

867799
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 867160
type: Species

259051
units: 159727
value: 6.0E-12
type: LocalParameter

161327
local parameters: 259015
notes: k3*MAPK_slash_Raf_minus_GTP_minus_Ras_star__slash_Raf_minus_GTP_minus_Ras_star__dot_1_slash_Raf_minus_GTP_minus_Ras_star__dot_1_cplx
type: KineticLaw

868479
kinetic law: 160698
product: 160685
reactant: 160673
notes: This is extremely slow (1e-4), but it is significant as so little GAP actually gets complexed with it that the total GTP turnover rises only by 2-3 X (see Gibbs et al, JBC 265(33) 20437-20422) and Eccleston et al JBC 268(36) 27012-27019 kf = 1e-4
fast: false
reversible: true
type: Reaction

161583
stoichiometry: 1.0
species: 867480
type: SpeciesReference

867919
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 867160
type: Species

161474
local parameters: 259026
local parameters: 259023
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

868899
kinetic law: 161717
product: 161704
product: 161692
reactant: 161680
fast: false
reversible: false
type: Reaction

162745
stoichiometry: 1.0
species: 867919
type: SpeciesReference

868419
kinetic law: 160588
product: 160576
reactant: 160564
reactant: 160552
notes: To start off, same kinetics as the PLA2-Ca-act direct pathway. Oops ! Missed out the Ca input to this pathway first time round. Let\'s raise the forward rate about 3x to 5e-6. This will let us reduce the rather high rates we have used for the kenz on PLA2*-Ca. In fact, it may be that the rates are not that different, just that this pathway for getting the PLA2 to the memb is more efficien....
fast: false
reversible: true
type: Reaction

161291
stoichiometry: 1.0
species: 867440
type: SpeciesReference

162127
stoichiometry: 1.0
species: 867559
type: SpeciesReference

867739
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 867160
type: Species

160624
local parameters: 258979
local parameters: 258976
notes: kf*PLA2_slash_PLA2_star_-kb*PLA2_slash_PLA2_minus_cytosolic
type: KineticLaw

161029
local parameters: 258997
notes: k3*PKC_minus_active_slash_PKC_minus_act_minus_GEF_slash_PKC_minus_act_minus_GEF_cplx
type: KineticLaw

868159
kinetic law: 159921
product: 159909
reactant: 159896
reactant: 159884
notes: Need est of rate. Assume it is fast Obtained from param search kf raised 10 X : see Shinomura et al PNAS 88 5149-5153 1991. kf changed from 3.865e-7 to 2.0e-7 in line with closer analysis of Shinomura data. 26 June 1996: Corrected DAG data: reduce kf 15x from 2e-7 to 1.333e-8
fast: false
reversible: true
type: Reaction

159896
stoichiometry: 1.0
species: 867179
type: SpeciesReference

160527
stoichiometry: 1.0
species: 868059
type: SpeciesReference

868819
kinetic law: 161522
product: 161510
product: 161498
reactant: 161486
fast: false
reversible: false
type: Reaction

160588
local parameters: 258974
local parameters: 258973
notes: kf*PLA2_slash_PLA2_star_*Ca-kb*PLA2_slash_PLA2_star__minus_Ca
type: KineticLaw

259050
units: 159727
value: 2.5E-11
type: LocalParameter

161632
stoichiometry: 1.0
species: 867380
type: SpeciesReference

160576
stoichiometry: 1.0
species: 867819
type: SpeciesReference

258952
units: 159727
value: 5.0E-11
type: LocalParameter

161680
stoichiometry: 1.0
species: 867519
type: SpeciesReference

258942
units: 159727
value: 8.6348E-12
type: LocalParameter

161414
stoichiometry: 1.0
species: 867439
type: SpeciesReference

868619
kinetic law: 161029
product: 161016
product: 161003
reactant: 160990
fast: false
reversible: false
type: Reaction

161921
stoichiometry: 1.0
species: 867399
type: SpeciesReference

867300
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 867160
type: Species

867719
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 867160
type: Species

259069
units: 159727
value: 6.0E-12
type: LocalParameter

162466
stoichiometry: 1.0
species: 867299
type: SpeciesReference

159981
stoichiometry: 1.0
species: 867219
type: SpeciesReference

258979
units: 159727
value: 0.0
type: LocalParameter

161095
stoichiometry: 1.0
species: 867400
type: SpeciesReference

258969
units: 159763
value: 3.0E-15
type: LocalParameter

259077
units: 159763
value: 2.76E-12
type: LocalParameter

258951
units: 159727
value: 1.0E-12
type: LocalParameter

161016
stoichiometry: 1.0
species: 868099
type: SpeciesReference

161486
stoichiometry: 1.0
species: 867479
type: SpeciesReference

258941
units: 159763
value: 7.9998E-15
type: LocalParameter

869039
kinetic law: 162055
product: 162042
reactant: 162030
reactant: 162018
fast: false
reversible: true
type: Reaction

161339
stoichiometry: 1.0
species: 867420
type: SpeciesReference

259068
units: 159727
value: 2.5E-11
type: LocalParameter

159799
exponent: -1.0
scale: 0
multipler: 1.0
kind: SECOND
type: SBMLUnit