445353
kinetic law: 467058
product: 467045
reactant: 467033
reactant: 467021
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

464027
stoichiometry: 1.0
species: 441534
type: SpeciesReference

468690
local parameters: 353090
notes: k3*Ras_slash_GEF_minus_Gprot_minus_bg_slash_GEF_minus_bg_act_minus_ras_slash_GEF_minus_bg_act_minus_ras_cplx
type: KineticLaw

439574
constant: false
boundary condition: false
has only substance units: false
initial concentration: 1.75E-16
initial amount: NaN
in compartment: 439494
type: Species

467070
stoichiometry: 1.0
species: 440194
type: SpeciesReference

468003
stoichiometry: 1.0
species: 440814
type: SpeciesReference

463218
stoichiometry: 1.0
species: 440354
type: SpeciesReference

441394
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

445453
kinetic law: 467318
product: 467305
product: 467292
product: 467279
reactant: 467267
fast: false
reversible: false
type: Reaction

462833
stoichiometry: 1.0
species: 443114
type: SpeciesReference

468834
local parameters: 353098
local parameters: 353095
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

470022
local parameters: 353183
local parameters: 353180
notes: k1*CaMKII_slash_CaMKII_minus_CaM*CaMKII_slash_tot_autonomous_CaMKII-k2*CaMKII_slash_tot_autonomous_CaMKII_slash_auton_286_slash_auton_286_cplx
type: KineticLaw

464921
stoichiometry: 1.0
species: 442434
type: SpeciesReference

467979
stoichiometry: 1.0
species: 440854
type: SpeciesReference

469052
stoichiometry: 1.0
species: 441234
type: SpeciesReference

467712
stoichiometry: 1.0
species: 440754
type: SpeciesReference

442814
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.015
initial amount: NaN
in compartment: 439494
type: Species

353222
units: 462030
value: 5.25E-16
type: LocalParameter

353318
units: 462115
value: 3.78E-15
type: LocalParameter

466768
local parameters: 353014
local parameters: 353011
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

445313
kinetic law: 466960
product: 466948
reactant: 466936
reactant: 466924
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

447273
kinetic law: 471770
product: 471757
product: 471745
reactant: 471733
fast: false
reversible: false
type: Reaction

442374
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

442914
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

445393
kinetic law: 467155
product: 467143
reactant: 467131
reactant: 467119
notes: See Porfiri and McCormick JBC 271:10 pp5871 1996 for the existence of this step. We\'ll take the rates from the ones used for the phosph of Raf by MAPK. Sep 17 1997: The transient activation curve matches better with k1 up by 10 x.
fast: false
reversible: true
type: Reaction

441354
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

471216
stoichiometry: 1.0
species: 442714
type: SpeciesReference

469574
stoichiometry: 1.0
species: 443214
type: SpeciesReference

464171
stoichiometry: 1.0
species: 441574
type: SpeciesReference

463979
stoichiometry: 1.0
species: 441434
type: SpeciesReference

466478
local parameters: 353002
local parameters: 352999
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

442994
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

464498
local parameters: 352898
local parameters: 352897
notes: kf*CaMKII_slash_CaMKII_minus_thr286*CaM_minus_Ca4-kb*CaMKII_slash_CaMKII_minus_thr286_star__minus_CaM
type: KineticLaw

464522
stoichiometry: 1.0
species: 441834
type: SpeciesReference

446433
kinetic law: 469731
product: 469719
reactant: 469707
reactant: 469695
notes: Rates from autocamtide phosphorylation, from Hanson and Schulman JBC 267:24 17216-17224 1992. Jan 1 1998: Speed up 12x to match fig 5.
fast: false
reversible: true
type: Reaction

446233
kinetic law: 469223
product: 469211
reactant: 469198
reactant: 469185
notes: Same rates as PKA-phosph-I1
fast: false
reversible: true
type: Reaction

464135
local parameters: 352876
local parameters: 352875
notes: kf*Sos_slash_Sos_dot_Grb2*EGFR_slash_SHC_star_-kb*Shc_star__dot_Sos_dot_Grb2
type: KineticLaw

462761
local parameters: 352786
local parameters: 352785
notes: kf*temp_minus_PIP2*PLA2_slash_PLA2_minus_Ca_star_-kb*PLA2_slash_PIP2_minus_Ca_minus_PLA2_star_
type: KineticLaw

463290
local parameters: 352822
local parameters: 352819
notes: kf*Gq_slash_mGluR*Glu-kb*Gq_slash_Rec_minus_Glu
type: KineticLaw

470848
local parameters: 353258
notes: k3*CaM_po_Ca_pc_n_minus_CaNAB_slash_dephosph_minus_PP1_minus_I_star__slash_dephosph_minus_PP1_minus_I_star__cplx
type: KineticLaw

446473
kinetic law: 469828
product: 469816
reactant: 469804
reactant: 469792
fast: false
reversible: true
type: Reaction

465271
stoichiometry: 1.0
species: 442594
type: SpeciesReference

471481
local parameters: 353324
notes: k3*AC_slash_cAMP_minus_PDE_slash_PDE_slash_PDE_cplx
type: KineticLaw

465126
stoichiometry: 1.0
species: 442714
type: SpeciesReference

468714
stoichiometry: 1.0
species: 441094
type: SpeciesReference

462176
exponent: 1.0
scale: -6
multipler: 1.0
kind: MOLE
type: SBMLUnit

467919
local parameters: 353057
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

464897
stoichiometry: 1.0
species: 442394
type: SpeciesReference

465235
stoichiometry: 1.0
species: 442594
type: SpeciesReference

470423
stoichiometry: 1.0
species: 442034
type: SpeciesReference

444833
kinetic law: 465802
product: 465790
reactant: 465778
reactant: 465766
notes: 18 May 2003. This reaction is here to provide basal activity for MAPK as well as the potential for direct EGF stimulus without PKC activation. Based on model from FB/fb28c.g: the model used for MKP-1 turnover. The rates there were constrained by basal activity values.
fast: false
reversible: true
type: Reaction

353047
units: 462115
value: 1.41426E-14
type: LocalParameter

467204
local parameters: 353030
notes: k3*MAPK_star__slash_phosph_Sos_slash_phosph_Sos_cplx
type: KineticLaw

468437
stoichiometry: 1.0
species: 440994
type: SpeciesReference

462420
stoichiometry: 1.0
species: 439554
type: SpeciesReference

463074
stoichiometry: 1.0
species: 440274
type: SpeciesReference

440294
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

471673
local parameters: 353342
notes: k3*AC_slash_PDE1_slash_PDE1_slash_PDE1_cplx
type: KineticLaw

468111
local parameters: 353066
notes: k3*MKP_minus_1_slash_MKP1_minus_tyr_minus_deph_slash_MKP1_minus_tyr_minus_deph_cplx
type: KineticLaw

468087
stoichiometry: 1.0
species: 440614
type: SpeciesReference

465548
stoichiometry: 1.0
species: 443054
type: SpeciesReference

466912
local parameters: 353018
notes: k3*PLA2_slash_PLA2_star__minus_Ca_slash_kenz_slash_kenz_cplx
type: KineticLaw

467602
stoichiometry: 1.0
species: 440154
type: SpeciesReference

440934
constant: false
boundary condition: false
has only substance units: false
initial concentration: 1.0
initial amount: NaN
in compartment: 439494
type: Species

471445
stoichiometry: 1.0
species: 442914
type: SpeciesReference

445913
kinetic law: 468449
product: 468437
reactant: 468425
reactant: 468413
fast: false
reversible: true
type: Reaction

463037
stoichiometry: 1.0
species: 443194
type: SpeciesReference

465995
stoichiometry: 1.0
species: 439814
type: SpeciesReference

441714
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

444433
kinetic law: 464861
product: 464849
product: 464836
reactant: 464824
notes: Let us assume that the equil in this case is very far over to the right. This is probably safe.
fast: false
reversible: true
type: Reaction

462286
stoichiometry: 1.0
species: 439534
type: SpeciesReference

469392
stoichiometry: 1.0
species: 441454
type: SpeciesReference

471142
local parameters: 353285
notes: k3*CaNAB_minus_Ca4_slash_dephosph_inhib1_noCaM_slash_dephosph_inhib1_noCaM_cplx
type: KineticLaw

467578
local parameters: 353044
local parameters: 353043
notes: k1*MAPK_slash_MAPK_minus_tyr*MAPK_slash_MAPKK_star_-k2*MAPK_slash_MAPKK_star__slash_MAPKKthr_slash_MAPKKthr_cplx
type: KineticLaw

469465
local parameters: 353131
notes: k3*EGFR_slash_L_dot_EGFR_slash_phosph_PLC_g_slash_phosph_PLC_g_cplx
type: KineticLaw

468750
stoichiometry: 1.0
species: 441114
type: SpeciesReference

441754
constant: false
boundary condition: false
has only substance units: false
initial concentration: 70.0
initial amount: NaN
in compartment: 439494
type: Species

462236
stoichiometry: 1.0
species: 439754
type: SpeciesReference

462506
stoichiometry: 1.0
species: 439654
type: SpeciesReference

466960
local parameters: 353020
local parameters: 353019
notes: k1*PLA2_slash_PLA2_minus_cytosolic*MAPK_star_-k2*MAPK_star__slash_MAPK_star__slash_MAPK_star__cplx
type: KineticLaw

353043
units: 462115
value: 4.86E-14
type: LocalParameter

443234
notes: I am implementing this as acting only on the Rec-Gq complex, based on a more complete model PLC_Gq48.g which showed that the binding to the rec alone contributed only a small amount.
constant: true
boundary condition: true
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

465947
stoichiometry: 1.0
species: 441194
type: SpeciesReference

352980
units: 462115
value: 9.000045E-15
type: LocalParameter

353110
units: 462030
value: 5.4E-14
type: LocalParameter

353002
units: 462030
value: 3.24E-14
type: LocalParameter

464740
stoichiometry: 1.0
species: 442114
type: SpeciesReference

467809
stoichiometry: 1.0
species: 440754
type: SpeciesReference

470752
local parameters: 353249
notes: k3*CaM_po_Ca_pc_n_minus_CaNAB_slash_dephosph_inhib1_slash_dephosph_inhib1_cplx
type: KineticLaw

466163
stoichiometry: 1.0
species: 439854
type: SpeciesReference

353042
units: 462030
value: 4.5E-16
type: LocalParameter

466696
stoichiometry: 1.0
species: 439774
type: SpeciesReference

465439
local parameters: 352954
local parameters: 352953
notes: kf*PKA_minus_active*PKA_slash_PKA_minus_inhibitor-kb*PKA_slash_inhibited_minus_PKA
type: KineticLaw

352907
units: 462115
value: 6.975045E-16
type: LocalParameter

353003
units: 462030
value: 8.1E-15
type: LocalParameter

470971
stoichiometry: 1.0
species: 442334
type: SpeciesReference

469792
stoichiometry: 1.0
species: 441774
type: SpeciesReference

353041
units: 462030
value: 1.8E-15
type: LocalParameter

441174
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

353045
units: 462030
value: 4.5E-16
type: LocalParameter

462091
exponent: -2.0
scale: -6
multipler: 1.0
kind: MOLE
type: SBMLUnit

467422
stoichiometry: 1.0
species: 440314
type: SpeciesReference

469100
stoichiometry: 1.0
species: 441294
type: SpeciesReference

440434
constant: false
boundary condition: false
has only substance units: false
initial concentration: 1.0
initial amount: NaN
in compartment: 439494
type: Species

353004
units: 462115
value: 4.140045E-15
type: LocalParameter

445893
kinetic law: 468401
product: 468389
product: 468377
reactant: 468365
fast: false
reversible: false
type: Reaction

446653
kinetic law: 470265
product: 470252
product: 470240
reactant: 470228
fast: false
reversible: false
type: Reaction

352982
units: 462030
value: 6.0E-15
type: LocalParameter

443873
kinetic law: 463520
product: 463508
reactant: 463496
reactant: 463484
notes: From Fay et al kb3 = kb = 1.06e-3 which is rather slow. k+1 = kf = 2.8e7 /M/sec= 4.67e-5/sec use 5e-5. However, the Kd from Martin et al may be more appropriate, as this is Glu not the system from Fay. kf = 2.8e-5, kb = 10 Let us compromise. since we have the Fay model, keep kf = k+1 = 2.8e-5. But kb (k-3) is .01 * k-1 from Fay. Scaling by .01, kb = .01 * 10 = 0.1
fast: false
reversible: true
type: Reaction

468641
local parameters: 353089
local parameters: 353088
notes: k1*Ras_slash_GDP_minus_Ras*Ras_slash_GEF_minus_Gprot_minus_bg-k2*Ras_slash_GEF_minus_Gprot_minus_bg_slash_GEF_minus_bg_act_minus_ras_slash_GEF_minus_bg_act_minus_ras_cplx
type: KineticLaw

468944
stoichiometry: 1.0
species: 441274
type: SpeciesReference

353044
units: 462030
value: 1.8E-15
type: LocalParameter

445853
kinetic law: 468305
product: 468293
product: 468281
reactant: 468268
fast: false
reversible: false
type: Reaction

462615
local parameters: 352778
local parameters: 352777
notes: kf*PKC_slash_PKC_minus_DAG*AA-kb*PKC_slash_PKC_minus_DAG_minus_AA
type: KineticLaw

463773
local parameters: 352850
local parameters: 352849
notes: kf*BetaGamma*Ras_slash_inact_minus_GEF-kb*Ras_slash_GEF_minus_Gprot_minus_bg
type: KineticLaw

441594
constant: false
boundary condition: false
has only substance units: false
initial concentration: 1.0
initial amount: NaN
in compartment: 439494
type: Species

465343
local parameters: 352948
local parameters: 352947
notes: kf*PKA_slash_R2C2_minus_cAMP4-kb*PKA_minus_active*PKA_slash_R2C_minus_cAMP4
type: KineticLaw

469112
stoichiometry: 1.0
species: 441334
type: SpeciesReference

465199
local parameters: 352940
local parameters: 352939
notes: kf*PKA_slash_R2C2_minus_cAMP*cAMP-kb*PKA_slash_R2C2_minus_cAMP2
type: KineticLaw

463376
stoichiometry: 1.0
species: 440434
type: SpeciesReference

352981
units: 462030
value: 2.4E-14
type: LocalParameter

353005
units: 462030
value: 6.624E-14
type: LocalParameter

353312
units: 462030
value: 8.1E-14
type: LocalParameter

443874
product: 463544
fast: false
reversible: true
notes: This is the kcat==k3 stage of the Rec-Glu ezymatic activation of Gq. From Berstein et al actiation is at .35 - 0.7/min From Fay et al Biochem 30 5066-5075 1991 kf = .01/sec From Nakamura et al J physiol Lond 474:1 35-41 1994 see time courses. Also (Berstein) 15-40% of gprot is in GTP-bound form on stim.
product: 463569
type: Reaction
reactant: 463532
product: 463557
kinetic law: 463581

467131
stoichiometry: 1.0
species: 440154
type: SpeciesReference

463436
stoichiometry: 1.0
species: 440434
type: SpeciesReference

471252
stoichiometry: 1.0
species: 443274
type: SpeciesReference

444293
kinetic law: 464535
product: 464522
reactant: 464510
notes: This reaction represents one of the big unknowns in CaMK-II biochemistry: what maintains the basal level of phosphorylation on thr 286 ? See Hanson and Schulman Ann Rev Biochem 1992 61:559-601, specially pg 580, for review. I have not been able to find any compelling mechanism in the literature, but fortunately the level of basal activity is well documented.
fast: false
reversible: true
type: Reaction

443534
kinetic law: 462396
product: 462383
reactant: 462371
reactant: 462359
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

353098
units: 462030
value: 6.0E-14
type: LocalParameter

444693
kinetic law: 465487
product: 465475
reactant: 465463
reactant: 465451
notes: Half-max at 20 nM CaM (Tang et al JBC 266:13 8595-8603 1991 kb/kf = 20 nM = 12000 #/cell so kf = kb/12000 = kb * 8.333e-5
fast: false
reversible: true
type: Reaction

352984
units: 462030
value: 2.4E-14
type: LocalParameter

443194
notes: Phosphatidylcholine is the main (around 55%) metabolic product of DAG, follwed by PE (around 25%). Ref is Welsh and Cabot, JCB35:231-245(1987)
constant: true
boundary condition: true
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439514
type: Species

470680
stoichiometry: 1.0
species: 443354
type: SpeciesReference

470643
stoichiometry: 1.0
species: 443354
type: SpeciesReference

464704
stoichiometry: 1.0
species: 442074
type: SpeciesReference

444573
kinetic law: 465199
product: 465187
reactant: 465175
reactant: 465162
notes: For now let us set this to the same Km (1e-7M) as site B. This gives kf/kb = .7e-7M * 1e6 / (6e5^2) : 1/(6e5^2) = 2e-13:2.77e-12 Smith et al have better values. They say that this is cooperative, so the consts are now kf/kb =8.3e-4
fast: false
reversible: true
type: Reaction

353099
units: 462030
value: 1.5E-14
type: LocalParameter

467821
local parameters: 353054
notes: k3*MAPK_slash_Raf_minus_GTP_minus_Ras_slash_Raf_minus_GTP_minus_Ras_dot_2_slash_Raf_minus_GTP_minus_Ras_dot_2_cplx
type: KineticLaw

442634
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

463484
stoichiometry: 1.0
species: 443154
type: SpeciesReference

462725
stoichiometry: 1.0
species: 443134
type: SpeciesReference

467470
stoichiometry: 1.0
species: 440694
type: SpeciesReference

469538
stoichiometry: 1.0
species: 441534
type: SpeciesReference

352983
units: 462115
value: 9.000045E-15
type: LocalParameter

466055
stoichiometry: 1.0
species: 443294
type: SpeciesReference

465754
local parameters: 352972
local parameters: 352971
notes: kf*AC_slash_PDE1*CaM_minus_Ca4-kb*AC_slash_CaM_dot_PDE1
type: KineticLaw

353113
units: 462030
value: 5.4E-14
type: LocalParameter

465018
stoichiometry: 1.0
species: 442154
type: SpeciesReference

440514
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

353192
units: 462030
value: 2.1E-15
type: LocalParameter

442454
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

466115
stoichiometry: 1.0
species: 443294
type: SpeciesReference

466587
stoichiometry: 1.0
species: 439994
type: SpeciesReference

443114
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: 439494
type: Species

441534
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

470363
local parameters: 353213
notes: k3*PP1_minus_active_slash_Deph_minus_thr306_slash_Deph_minus_thr306_cplx
type: KineticLaw

444613
kinetic law: 465295
product: 465283
reactant: 465271
reactant: 465259
fast: false
reversible: true
type: Reaction

467530
local parameters: 353042
notes: k3*MAPK_slash_MAPKK_star__slash_MAPKKtyr_slash_MAPKKtyr_cplx
type: KineticLaw

444213
kinetic law: 464364
product: 464351
reactant: 464339
reactant: 464327
notes: Again, we refer to Homma et al and Wahl et al, for preference using Wahl. Half-Max of the phosph form is at 316 nM. Use kb of 10 as this is likely to be pretty fast. Did some curve comparisons, and instead of 316 nM giving a kf of 5.27e-5, we will use 8e-5 for kf. 16 Sep 97. As we are now phosphorylating the Ca-bound form, equils have shifted. kf should now be 2e-5 to match the curves.
fast: false
reversible: true
type: Reaction

353040
units: 462115
value: 4.86E-14
type: LocalParameter

353112
units: 462115
value: 9.000045E-15
type: LocalParameter

353315
units: 461994
value: 60.0
type: LocalParameter

470070
local parameters: 353186
notes: k3*CaMKII_slash_tot_autonomous_CaMKII_slash_auton_286_slash_auton_286_cplx
type: KineticLaw

445053
kinetic law: 466331
product: 466319
product: 466307
product: 466295
reactant: 466283
fast: false
reversible: false
type: Reaction

468605
stoichiometry: 1.0
species: 441154
type: SpeciesReference

352985
units: 462030
value: 6.0E-15
type: LocalParameter

464063
stoichiometry: 1.0
species: 441454
type: SpeciesReference

440554
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.5
initial amount: NaN
in compartment: 439494
type: Species

471529
local parameters: 353330
local parameters: 353327
notes: k1*cAMP*AC_slash_cAMP_minus_PDE_star_-k2*AC_slash_cAMP_minus_PDE_star__slash_PDE_star__slash_PDE_star__cplx
type: KineticLaw

353111
units: 462030
value: 1.35E-14
type: LocalParameter

352761
units: 462115
value: 1.799955E-18
type: LocalParameter

352987
units: 462115
value: 1.529955E-16
type: LocalParameter

352952
units: 462115
value: 2.7E-14
type: LocalParameter

463665
stoichiometry: 1.0
species: 440534
type: SpeciesReference

353105
units: 462030
value: 1.35E-14
type: LocalParameter

352807
units: 462115
value: 3.78E-14
type: LocalParameter

352911
units: 462115
value: 4.499955E-16
type: LocalParameter

353195
units: 462030
value: 5.25E-16
type: LocalParameter

466503
stoichiometry: 1.0
species: 439774
type: SpeciesReference

352875
units: 462115
value: 7.499655E-16
type: LocalParameter

445413
kinetic law: 467204
product: 467192
product: 467179
reactant: 467167
fast: false
reversible: false
type: Reaction

466732
stoichiometry: 1.0
species: 443114
type: SpeciesReference

464448
local parameters: 352896
local parameters: 352893
notes: kf*CaM_minus_Ca4*CaMKII_slash_CaMKII-kb*CaMKII_slash_CaMKII_minus_CaM
type: KineticLaw

442954
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

353093
units: 462030
value: 3.0E-17
type: LocalParameter

470289
stoichiometry: 1.0
species: 441954
type: SpeciesReference

470534
stoichiometry: 1.0
species: 441754
type: SpeciesReference

353156
units: 462030
value: 3.6E-14
type: LocalParameter

352806
units: 462030
value: 0.0
type: LocalParameter

468871
stoichiometry: 1.0
species: 441194
type: SpeciesReference

465826
stoichiometry: 1.0
species: 443074
type: SpeciesReference

352912
units: 462030
value: 1.5E-15
type: LocalParameter

440374
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

469647
stoichiometry: 1.0
species: 439754
type: SpeciesReference

352874
units: 462030
value: 4.95E-19
type: LocalParameter

353198
units: 462115
value: 5.147955E-16
type: LocalParameter

445493
kinetic law: 467434
product: 467422
product: 467409
product: 467396
reactant: 467383
fast: false
reversible: false
type: Reaction

471104
stoichiometry: 1.0
species: 442414
type: SpeciesReference

353103
units: 462115
value: 9.000045E-15
type: LocalParameter

442334
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.12
initial amount: NaN
in compartment: 439494
type: Species

352954
units: 462030
value: 1.5E-15
type: LocalParameter

353261
units: 462115
value: 5.94E-15
type: LocalParameter

442854
constant: false
boundary condition: false
has only substance units: false
initial concentration: 325493.333333333
initial amount: NaN
in compartment: 439514
type: Species

352877
units: 462115
value: 3.75003E-17
type: LocalParameter

352913
units: 462030
value: 7.5E-18
type: LocalParameter

470460
local parameters: 353222
notes: k3*PP1_minus_active_slash_Deph_minus_thr286c_slash_Deph_minus_thr286c_cplx
type: KineticLaw

353104
units: 462030
value: 5.4E-14
type: LocalParameter

466223
local parameters: 352991
notes: k3*PKC_minus_active_slash_PKC_minus_phosph_minus_neurogranin_slash_PKC_minus_phosph_minus_neurogranin_cplx
type: KineticLaw

352764
units: 462030
value: 1.5E-16
type: LocalParameter

352953
units: 462115
value: 9.000045E-14
type: LocalParameter

353095
units: 462115
value: 7.42284E-14
type: LocalParameter

447113
kinetic law: 471385
modifier: 471373
product: 471361
reactant: 471349
fast: false
reversible: false
type: Reaction

352876
units: 462030
value: 1.5E-16
type: LocalParameter

471032
stoichiometry: 1.0
species: 442334
type: SpeciesReference

467021
stoichiometry: 1.0
species: 440574
type: SpeciesReference

464788
stoichiometry: 1.0
species: 441954
type: SpeciesReference

440834
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

469840
stoichiometry: 1.0
species: 441894
type: SpeciesReference

446313
kinetic law: 469416
product: 469404
reactant: 469392
reactant: 469380
notes: Hsu et al JBC 266:1 603-608 1991 Km = 385 +- 100 uM, Vm = 5.1 +-1 pmol/min/ug for PLC-771. Other sites have similar range, but are not stim as much by EGF. k1 = 2.8e-2/385/6e5 = 1.2e-10. Phenomenally slow. But Sherrill and Kyte say turnover # for angiotensin II is 5/min for cell extt, and 2/min for placental. Also see Okada et al for Shc rates which are much faster.
fast: false
reversible: true
type: Reaction

469211
stoichiometry: 1.0
species: 441354
type: SpeciesReference

352803
units: 462030
value: 3.75E-15
type: LocalParameter

465536
stoichiometry: 1.0
species: 442814
type: SpeciesReference

471337
local parameters: 353309
local parameters: 353306
notes: kcat*AC_slash_AC1_minus_Gs*AC_slash_ATP/(Km+AC_slash_ATP)
type: KineticLaw

353090
units: 462030
value: 3.0E-17
type: LocalParameter

352765
units: 462030
value: 3.0E-15
type: LocalParameter

440774
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

464680
local parameters: 352910
local parameters: 352907
notes: kf*CaM_minus_Ca3*Ca-kb*CaM_minus_Ca4
type: KineticLaw

467396
stoichiometry: 1.0
species: 439754
type: SpeciesReference

471745
stoichiometry: 1.0
species: 442854
type: SpeciesReference

353159
units: 462030
value: 9.0E-15
type: LocalParameter

463557
stoichiometry: 1.0
species: 440374
type: SpeciesReference

443753
kinetic law: 462977
product: 462965
reactant: 462953
reactant: 462941
notes: Affinity for Ca = 1uM without AlF, 0.1 with: from Smrcka et al science 251 pp 804-807 1991 so [Ca].kf = kb so kb/kf = 1 * 6e5 = 1/1.66e-6 11 June 1996: Raised affinity to 5e-6 to maintain balance. See notes.
fast: false
reversible: true
type: Reaction

463266
stoichiometry: 1.0
species: 443154
type: SpeciesReference

352802
units: 462030
value: 1.5E-15
type: LocalParameter

441694
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

352955
units: 462115
value: 7.499925E-14
type: LocalParameter

442094
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

352766
units: 462030
value: 3.0E-16
type: LocalParameter

470216
local parameters: 353201
local parameters: 353198
notes: k1*CaMKII_slash_CaMKII_star__star__star_*PP1_minus_active-k2*PP1_minus_active_slash_Deph_minus_thr305_slash_Deph_minus_thr305_cplx
type: KineticLaw

465487
local parameters: 352958
local parameters: 352955
notes: kf*CaM_minus_Ca4*AC_slash_AC1-kb*AC_slash_AC1_minus_CaM
type: KineticLaw

468581
stoichiometry: 1.0
species: 440934
type: SpeciesReference

443793
kinetic law: 463146
product: 463134
product: 463122
reactant: 463110
notes: This process is assumed to be directly caused by the inactivation of the G*GTP to G*GDP. Hence, kf = .013 /sec = 0.8/min, same as the rate for Inact-G. kb = 0 since this is irreversible. We may be interested in studying the role of PLC as a GAP. If so, the kf would be faster here than in Inact-G
fast: false
reversible: true
type: Reaction

440214
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

352916
units: 462030
value: 0.0
type: LocalParameter

467242
stoichiometry: 1.0
species: 440294
type: SpeciesReference

466331
local parameters: 352994
notes: k3*PKC_minus_active_slash_PKC_minus_phosph_minus_ng_minus_CaM_slash_PKC_minus_phosph_minus_ng_minus_CaM_cplx
type: KineticLaw

442674
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.25
initial amount: NaN
in compartment: 439494
type: Species

462953
stoichiometry: 1.0
species: 440254
type: SpeciesReference

471191
local parameters: 353291
local parameters: 353288
notes: kcat*AC_slash_AC1_minus_CaM*AC_slash_ATP/(Km+AC_slash_ATP)
type: KineticLaw

467357
stoichiometry: 1.0
species: 440334
type: SpeciesReference

464632
local parameters: 352906
local parameters: 352905
notes: kf*CaM_minus_TR2_minus_Ca2*Ca-kb*CaM_minus_Ca3
type: KineticLaw

353092
units: 462030
value: 1.2E-16
type: LocalParameter

353107
units: 462115
value: 9.000045E-15
type: LocalParameter

352767
units: 462030
value: 1.5E-15
type: LocalParameter

352958
units: 462030
value: 1.5E-15
type: LocalParameter

443794
kinetic law: 463194
product: 463182
reactant: 463170
reactant: 463158
notes: this binding does not produce active PLC. This step was needed to implement the described (Smrcka et al) increase in affinity for Ca by PLC once Gq was bound. The kinetics are the same as the binding step for Ca-PLC to Gq. June 1996: Changed the kf to 4.2e-5 to 4.2e-6 to preserve balance around the reactions.
fast: false
reversible: true
type: Reaction

352917
units: 462115
value: 7.499655E-13
type: LocalParameter

444033
kinetic law: 463967
product: 463954
reactant: 463942
fast: false
reversible: true
type: Reaction

469804
stoichiometry: 1.0
species: 443314
type: SpeciesReference

440974
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

352805
units: 462030
value: 2.25E-16
type: LocalParameter

465162
stoichiometry: 1.0
species: 442554
type: SpeciesReference

352873
units: 462030
value: 3.0E-18
type: LocalParameter

353091
units: 462115
value: 2.97E-16
type: LocalParameter

469755
stoichiometry: 1.0
species: 441814
type: SpeciesReference

441934
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

352804
units: 462030
value: 0.0
type: LocalParameter

352918
units: 462030
value: 1.5E-16
type: LocalParameter

464243
stoichiometry: 1.0
species: 441654
type: SpeciesReference

462128
exponent: 2.0
scale: 0
multipler: 1.0
kind: LITRE
type: SBMLUnit

442054
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

470570
stoichiometry: 1.0
species: 442114
type: SpeciesReference

352872
units: 462030
value: 0.0
type: LocalParameter

444073
kinetic law: 464051
product: 464039
reactant: 464027
notes: Time course of decline of phosph is 20 min. Part of this is the turnoff time of the EGFR itself. Lets assume a tau of 10 min for this dephosph. It may be wildly off.
fast: false
reversible: true
type: Reaction

469004
stoichiometry: 1.0
species: 441294
type: SpeciesReference

443754
kinetic law: 463013
product: 463001
reactant: 462989
notes: The enzyme is IP3 5-phosphomonesterase. about 45K. Actual products are Ins(1,4)P2, and cIns(1:2,4,5)P3. review in Majerus et al Science 234 1519-1526, 1986. Meyer and Stryer 1988 PNAS 85:5051-5055 est decay of IP3 at 1-3/sec
fast: false
reversible: true
type: Reaction

468160
local parameters: 353068
local parameters: 353067
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

463617
stoichiometry: 1.0
species: 440494
type: SpeciesReference

462396
local parameters: 352764
local parameters: 352761
notes: kf*PKC_slash_PKC_minus_Ca*AA-kb*PKC_slash_PKC_minus_Ca_minus_AA_star_
type: KineticLaw

469271
local parameters: 353115
notes: k3*PKA_minus_active_slash_phosph_minus_PDE_slash_phosph_minus_PDE_cplx
type: KineticLaw

465597
stoichiometry: 1.0
species: 442754
type: SpeciesReference

446013
kinetic law: 468690
product: 468678
product: 468666
reactant: 468654
fast: false
reversible: false
type: Reaction

465645
stoichiometry: 1.0
species: 442774
type: SpeciesReference

464351
stoichiometry: 1.0
species: 441734
type: SpeciesReference

463930
local parameters: 352862
local parameters: 352861
notes: kf*Ras_slash_inact_minus_GEF*CaM_minus_Ca4-kb*Ras_slash_CaM_minus_GEF
type: KineticLaw

468473
stoichiometry: 1.0
species: 440594
type: SpeciesReference

446693
kinetic law: 470363
product: 470351
product: 470338
reactant: 470325
fast: false
reversible: false
type: Reaction

466019
stoichiometry: 1.0
species: 443294
type: SpeciesReference

439734
constant: false
boundary condition: false
has only substance units: false
initial concentration: 1.0
initial amount: NaN
in compartment: 439494
type: Species

468196
stoichiometry: 1.0
species: 440874
type: SpeciesReference

352959
units: 462030
value: 1.5E-16
type: LocalParameter

469368
local parameters: 353122
notes: k3*Shc_star__dot_Sos_dot_Grb2_slash_Sos_dot_Ras_GEF_slash_Sos_dot_Ras_GEF_cplx
type: KineticLaw

468220
stoichiometry: 1.0
species: 440574
type: SpeciesReference

470240
stoichiometry: 1.0
species: 441834
type: SpeciesReference

446373
kinetic law: 469562
product: 469550
product: 469538
reactant: 469526
fast: false
reversible: false
type: Reaction

471637
stoichiometry: 1.0
species: 442994
type: SpeciesReference

464400
local parameters: 352892
local parameters: 352891
notes: kf*PLC_g_slash_Ca_dot_PLC_g_star_-kb*PLC_g_slash_Ca_dot_PLC_g
type: KineticLaw

469914
stoichiometry: 1.0
species: 441914
type: SpeciesReference

353219
units: 462030
value: 2.1E-15
type: LocalParameter

462653
stoichiometry: 1.0
species: 439934
type: SpeciesReference

470325
stoichiometry: 1.0
species: 442014
type: SpeciesReference

471092
local parameters: 353282
local parameters: 353279
notes: k1*PP1_slash_I1_star_*CaNAB_minus_Ca4-k2*CaNAB_minus_Ca4_slash_dephosph_inhib1_noCaM_slash_dephosph_inhib1_noCaM_cplx
type: KineticLaw

470130
stoichiometry: 1.0
species: 441974
type: SpeciesReference

447053
kinetic law: 471240
modifier: 471228
product: 471216
reactant: 471203
notes: Reduced Km to match expt data for basal activation of AC2 by PKC. Now k1 = 2.9e-6, k2 = 72, k3 = 18
fast: false
reversible: false
type: Reaction

446613
kinetic law: 470167
product: 470155
product: 470142
reactant: 470130
fast: false
reversible: false
type: Reaction

442154
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

441134
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

469429
stoichiometry: 1.0
species: 441474
type: SpeciesReference

466271
local parameters: 352993
local parameters: 352992
notes: k1*CaM_slash_neurogranin_minus_CaM*PKC_minus_active-k2*PKC_minus_active_slash_PKC_minus_phosph_minus_ng_minus_CaM_slash_PKC_minus_phosph_minus_ng_minus_CaM_cplx
type: KineticLaw

463725
local parameters: 352848
local parameters: 352845
notes: kf*MAPK_slash_craf_minus_1_star_*Ras_slash_GTP_minus_Ras-kb*MAPK_slash_Raf_star__minus_GTP_minus_Ras
type: KineticLaw

463870
stoichiometry: 1.0
species: 441194
type: SpeciesReference

353216
units: 462115
value: 5.147955E-16
type: LocalParameter

467688
stoichiometry: 1.0
species: 440774
type: SpeciesReference

468377
stoichiometry: 1.0
species: 440734
type: SpeciesReference

463110
stoichiometry: 1.0
species: 440314
type: SpeciesReference

470921
stoichiometry: 1.0
species: 442254
type: SpeciesReference

462457
stoichiometry: 1.0
species: 439634
type: SpeciesReference

442114
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

439794
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

445133
kinetic law: 466527
product: 466515
product: 466503
reactant: 466490
fast: false
reversible: false
type: Reaction

444093
kinetic law: 464087
product: 464075
reactant: 464063
notes: See Helin and Beguinot JBC 266:13 1991 pg 8363-8368. In Fig 3 they have internalization tau about 10 min, equil at about 20% EGF available. So kf = 4x kb, and 1/(kf + kb) = 600 sec so kb = 1/3K = 3.3e-4, and kf = 1.33e-3. This doesn\'t take into account the unbound receptor, so we need to push the kf up a bit, to 0.002
fast: false
reversible: true
type: Reaction

462542
stoichiometry: 1.0
species: 439754
type: SpeciesReference

445673
kinetic law: 467870
product: 467858
reactant: 467846
reactant: 467834
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

441454
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

469950
stoichiometry: 1.0
species: 441814
type: SpeciesReference

444713
kinetic law: 465524
product: 465511
reactant: 465499
notes: Random rate.
fast: false
reversible: true
type: Reaction

445733
kinetic law: 468015
product: 468003
product: 467991
reactant: 467979
fast: false
reversible: false
type: Reaction

463327
stoichiometry: 1.0
species: 440374
type: SpeciesReference

464339
stoichiometry: 1.0
species: 441694
type: SpeciesReference

446173
kinetic law: 469076
product: 469064
product: 469052
reactant: 469040
fast: false
reversible: false
type: Reaction

353264
units: 462030
value: 3.75E-14
type: LocalParameter

353150
units: 461994
value: 19.7916666666667
type: LocalParameter

470179
stoichiometry: 1.0
species: 441814
type: SpeciesReference

462079
exponent: 3.0
scale: 0
multipler: 1.0
kind: LITRE
type: SBMLUnit

446813
kinetic law: 470655
product: 470643
product: 470631
reactant: 470619
fast: false
reversible: false
type: Reaction

465717
stoichiometry: 1.0
species: 442974
type: SpeciesReference

468980
local parameters: 353102
notes: k3*Ras_slash_CaM_minus_GEF_slash_CaM_minus_GEF_minus_act_minus_ras_slash_CaM_minus_GEF_minus_act_minus_ras_cplx
type: KineticLaw

465609
stoichiometry: 1.0
species: 442834
type: SpeciesReference

465054
local parameters: 352932
local parameters: 352931
notes: kf*CaM_minus_Ca3*CaNAB_minus_Ca4-kb*PP2B_slash_CaMCa3_minus_CaNAB
type: KineticLaw

442494
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

462347
local parameters: 352760
local parameters: 352759
notes: kf*PKC_slash_PKC_minus_Ca_minus_DAG-kb*PKC_slash_PKC_minus_DAG_minus_memb_star_
type: KineticLaw

444653
kinetic law: 465391
product: 465379
product: 465367
reactant: 465355
fast: false
reversible: true
type: Reaction

463182
stoichiometry: 1.0
species: 440354
type: SpeciesReference

353153
units: 462115
value: 3.961305E-16
type: LocalParameter

469683
local parameters: 353150
local parameters: 353147
notes: kcat*PLC_g_slash_Ca_dot_PLC_g_star_*PIP2/(Km+PIP2)
type: KineticLaw

463833
stoichiometry: 1.0
species: 441154
type: SpeciesReference

464571
stoichiometry: 1.0
species: 442174
type: SpeciesReference

444993
kinetic law: 466175
product: 466163
reactant: 466151
reactant: 466139
notes: Rates from Huang et al ABB 305:2 570-580 1993
fast: false
reversible: true
type: Reaction

440074
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

439634
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

443154
notes: Varying the amount of (steady state) glu between .01 uM and up, the final amount of G*GTP complex does not change much. This means that the system should be reasonably robust wr to the amount of glu in the synaptic cleft. It would be nice to know how fast it is removed.
constant: true
boundary condition: true
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

470897
local parameters: 353264
local parameters: 353261
notes: k1*PP1_slash_I1_star_*PP2A-k2*PP2A_slash_PP2A_minus_dephosph_minus_I1_slash_PP2A_minus_dephosph_minus_I1_cplx
type: KineticLaw

470812
stoichiometry: 1.0
species: 442234
type: SpeciesReference

467797
stoichiometry: 1.0
species: 440674
type: SpeciesReference

352910
units: 462030
value: 1.5E-14
type: LocalParameter

466840
stoichiometry: 1.0
species: 440094
type: SpeciesReference

440034
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

468268
stoichiometry: 1.0
species: 440954
type: SpeciesReference

446993
kinetic law: 471092
product: 471080
reactant: 471068
reactant: 471056
notes: The rates here are so slow I do not know if we should even bother with this enz reacn. These numbers are from Liu and Storm. Other refs suggest that the Km stays the same but the Vmax goes to 10% of the CaM stim levels. Prev: k1=2.2e-9, k2 = 0.0052, k3 = 0.0013 New : k1=5.7e-8, k2=.136, k3=.034
fast: false
reversible: true
type: Reaction

353267
units: 462030
value: 9.0E-15
type: LocalParameter

464824
stoichiometry: 1.0
species: 442314
type: SpeciesReference

467179
stoichiometry: 1.0
species: 441634
type: SpeciesReference

444953
kinetic law: 466079
product: 466067
reactant: 466055
reactant: 466043
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

444253
kinetic law: 464448
product: 464436
reactant: 464424
reactant: 464412
notes: This is tricky. There is some cooperativity here arising from interactions between the subunits of the CAMKII holoenzyme. However, the stoichiometry is 1. Kb/Kf = 6e4 #/cell. Rate is fast (see Hanson et al Neuron 12 943-956 1994) so lets say kb = 10. This gives kf = 1.6667e-4 H&S AnnRev Biochem 92 give tau for dissoc as 0.2 sec at low Ca, 0.4 at high. Low Ca = 100 nM = physiol.
fast: false
reversible: true
type: Reaction

469160
stoichiometry: 1.0
species: 441294
type: SpeciesReference

352760
units: 462030
value: 1.5E-16
type: LocalParameter

465874
stoichiometry: 1.0
species: 439794
type: SpeciesReference

443574
kinetic law: 462469
product: 462457
reactant: 462445
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

353213
units: 462030
value: 5.25E-16
type: LocalParameter

464183
local parameters: 352880
local parameters: 352877
notes: kf*Sos_slash_Sos_star_*Sos_slash_Grb2-kb*Sos_slash_Sos_star__dot_Grb2
type: KineticLaw

446573
kinetic law: 470070
product: 470058
product: 470046
reactant: 470034
fast: false
reversible: false
type: Reaction

464291
stoichiometry: 1.0
species: 443074
type: SpeciesReference

464535
local parameters: 352902
local parameters: 352899
notes: kf*CaMKII_slash_CaMKII-kb*CaMKII_slash_CaMKII_minus_thr286
type: KineticLaw

471601
stoichiometry: 1.0
species: 442974
type: SpeciesReference

469586
stoichiometry: 1.0
species: 439754
type: SpeciesReference

466307
stoichiometry: 1.0
species: 442114
type: SpeciesReference

463967
local parameters: 352866
local parameters: 352863
notes: kf*Ras_slash_inact_minus_GEF_star_-kb*Ras_slash_inact_minus_GEF
type: KineticLaw

352790
units: 462030
value: 6.0E-15
type: LocalParameter

463400
stoichiometry: 1.0
species: 440394
type: SpeciesReference

444473
kinetic law: 464957
product: 464945
reactant: 464933
reactant: 464921
notes: going on the experience with CaM, we put the fast (high affinity) sites first. We only know (Stemmer and Klee) that the affinity is < 70 nM. Assuming 10 nM at first, we get kf = 2.78e-8, kb = 1. Try 20 nM. kf = 7e-9, kb = 1
fast: false
reversible: true
type: Reaction

462773
stoichiometry: 1.0
species: 439754
type: SpeciesReference

466804
stoichiometry: 1.0
species: 440054
type: SpeciesReference

447233
kinetic law: 471673
product: 471661
product: 471649
reactant: 471637
fast: false
reversible: false
type: Reaction

464486
stoichiometry: 1.0
species: 441794
type: SpeciesReference

464147
stoichiometry: 1.0
species: 441634
type: SpeciesReference

465114
stoichiometry: 1.0
species: 442534
type: SpeciesReference

462188
stoichiometry: 1.0
species: 439734
type: SpeciesReference

466465
stoichiometry: 1.0
species: 439954
type: SpeciesReference

466091
stoichiometry: 1.0
species: 439834
type: SpeciesReference

468726
stoichiometry: 1.0
species: 441114
type: SpeciesReference

467217
stoichiometry: 1.0
species: 443214
type: SpeciesReference

467082
stoichiometry: 1.0
species: 440634
type: SpeciesReference

465910
stoichiometry: 1.0
species: 440574
type: SpeciesReference

468015
local parameters: 353063
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

440654
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

441034
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

470704
local parameters: 353246
local parameters: 353243
notes: k1*PP1_slash_I1_star_*CaM_po_Ca_pc_n_minus_CaNAB-k2*CaM_po_Ca_pc_n_minus_CaNAB_slash_dephosph_inhib1_slash_dephosph_inhib1_cplx
type: KineticLaw

464039
stoichiometry: 1.0
species: 441514
type: SpeciesReference

439954
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

466997
stoichiometry: 1.0
species: 440154
type: SpeciesReference

353039
units: 462030
value: 7.2E-14
type: LocalParameter

467724
local parameters: 353051
notes: k3*MAPK_slash_Raf_minus_GTP_minus_Ras_slash_Raf_minus_GTP_minus_Ras_dot_1_slash_Raf_minus_GTP_minus_Ras_dot_1_cplx
type: KineticLaw

469064
stoichiometry: 1.0
species: 441294
type: SpeciesReference

352792
units: 462030
value: 0.0
type: LocalParameter

464933
stoichiometry: 2.0
species: 443074
type: SpeciesReference

462845
local parameters: 352792
local parameters: 352791
notes: kf*AA-kb*PLA2_slash_APC
type: KineticLaw

470010
stoichiometry: 1.0
species: 441934
type: SpeciesReference

468822
stoichiometry: 1.0
species: 441214
type: SpeciesReference

440334
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

466756
stoichiometry: 1.0
species: 440074
type: SpeciesReference

469998
stoichiometry: 1.0
species: 443334
type: SpeciesReference

353210
units: 462030
value: 2.1E-15
type: LocalParameter

440734
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

440614
constant: false
boundary condition: false
has only substance units: false
initial concentration: 3.6
initial amount: NaN
in compartment: 439494
type: Species

470788
stoichiometry: 1.0
species: 442234
type: SpeciesReference

352791
units: 462030
value: 6.0E-16
type: LocalParameter

353038
units: 462030
value: 2.88E-13
type: LocalParameter

446153
kinetic law: 469028
product: 469016
reactant: 469004
reactant: 468992
notes: This pathway inhibits Ras when cAMP is elevated. See: Hordijk et al JBC 269:5 3534-3538 1994 Burgering et al EMBO J 12:11 4211-4220 1993 The rates are the same as used in PKA-phosph-I1
fast: false
reversible: true
type: Reaction

443334
constant: false
boundary condition: true
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

441634
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

469319
local parameters: 353119
local parameters: 353116
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

463025
stoichiometry: 1.0
species: 439754
type: SpeciesReference

441434
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.166666666666667
initial amount: NaN
in compartment: 439494
type: Species

467614
stoichiometry: 1.0
species: 440674
type: SpeciesReference

466900
stoichiometry: 1.0
species: 440094
type: SpeciesReference

469477
stoichiometry: 1.0
species: 441514
type: SpeciesReference

468762
stoichiometry: 1.0
species: 441134
type: SpeciesReference

471433
local parameters: 353321
local parameters: 353318
notes: k1*cAMP*AC_slash_cAMP_minus_PDE-k2*AC_slash_cAMP_minus_PDE_slash_PDE_slash_PDE_cplx
type: KineticLaw

469719
stoichiometry: 1.0
species: 441874
type: SpeciesReference

447173
kinetic law: 471529
product: 471517
reactant: 471505
reactant: 471493
notes: This form has about twice the activity of the unphosphorylated form. See Sette et al JBC 269:28 18271-18274 1994. We\'ll ignore cGMP effects for now.
fast: false
reversible: true
type: Reaction

462298
stoichiometry: 1.0
species: 439594
type: SpeciesReference

469380
stoichiometry: 1.0
species: 441714
type: SpeciesReference

443094
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

352793
units: 462115
value: 9.000045E-15
type: LocalParameter

462248
stoichiometry: 1.0
species: 439534
type: SpeciesReference

443014
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

462518
local parameters: 352772
local parameters: 352771
notes: kf*AA*PKC_slash_PKC_minus_cytosolic-kb*PKC_slash_PKC_minus_AA_star_
type: KineticLaw

471154
stoichiometry: 1.0
species: 443274
type: SpeciesReference

468281
stoichiometry: 1.0
species: 440554
type: SpeciesReference

467907
stoichiometry: 1.0
species: 440814
type: SpeciesReference

467292
stoichiometry: 1.0
species: 440234
type: SpeciesReference

353035
units: 462115
value: 7.199955E-14
type: LocalParameter

441854
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

443694
kinetic law: 462809
product: 462797
reactant: 462785
reactant: 462773
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

445953
kinetic law: 468545
product: 468533
reactant: 468521
reactant: 468509
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

352796
units: 462030
value: 1.5E-16
type: LocalParameter

467760
stoichiometry: 1.0
species: 440794
type: SpeciesReference

353249
units: 462030
value: 5.1E-16
type: LocalParameter

467192
stoichiometry: 1.0
species: 440154
type: SpeciesReference

469502
stoichiometry: 1.0
species: 441494
type: SpeciesReference

465223
stoichiometry: 1.0
species: 442714
type: SpeciesReference

470411
local parameters: 353219
local parameters: 353216
notes: k1*CaMKII_slash_CaMKII_star__star__star_*PP1_minus_active-k2*PP1_minus_active_slash_Deph_minus_thr286c_slash_Deph_minus_thr286c_cplx
type: KineticLaw

446393
reversible: false
modifier: 469611
fast: false
kinetic law: 469623
product: 469598
reactant: 469574
type: Reaction
notes: Mainly Homma et al JBC 263:14 1988 pp 6592, but these parms are the Ca-stimulated form. It is not clear whether the enzyme is activated by tyrosine phosphorylation at this point or not. Wahl et al JBC 267:15 10447-10456 1992 say that the Ca_stim and phosph form has 7X higher affinity for substrate than control. This is close to Wahl\'s figure 7, which I am using as reference.
product: 469586

466792
stoichiometry: 1.0
species: 439774
type: SpeciesReference

468075
stoichiometry: 1.0
species: 440894
type: SpeciesReference

445993
kinetic law: 468641
product: 468629
reactant: 468617
reactant: 468605
notes: Kinetics based on the activation of Gq by the receptor complex in the Gq model (in turn based on the Mahama and Linderman model) k1 = 2e-5, k2 = 1e-10, k3 = 10 (I do not know why they even bother with k2). Lets put k1 at 2e-6 to get a reasonable equilibrium More specific values from, eg.g: Orita et al JBC 268(34) 25542-25546 from rasGRF and smgGDS: k1=3.3e-7; k2 = 0.08, k3 = 0.02
fast: false
reversible: true
type: Reaction

468123
stoichiometry: 1.0
species: 440154
type: SpeciesReference

468425
stoichiometry: 1.0
species: 440934
type: SpeciesReference

471685
stoichiometry: 1.0
species: 442714
type: SpeciesReference

444313
kinetic law: 464583
product: 464571
reactant: 464559
reactant: 464547
notes: Lets use the fast rate consts here. Since the rates are so different, I am not sure whether the order is relevant. These correspond to the TR2C fragment. We use the Martin et al rates here, plus the Drabicowski binding consts. All are scaled by 3X to cell temp. kf = 2e-10 kb = 72 Stemmer & Klee: K1=.9, K2=1.1. Assume 1.0uM for both. kb/kf=3.6e11. If kb=72, kf = 2e-10 (Exactly the same !)....
fast: false
reversible: true
type: Reaction

441794
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

463062
stoichiometry: 1.0
species: 440394
type: SpeciesReference

443693
kinetic law: 462761
product: 462749
reactant: 462737
reactant: 462725
fast: false
reversible: true
type: Reaction

444393
kinetic law: 464764
product: 464752
reactant: 464740
notes: This is put in to keep the basal levels of neurogranin* experimentally reasonable. From various papers, specially Ramakers et al JBC 270:23 1995 13892-13898, it looks like the basal level of phosph is between 20 and 40%. I est around 25 % The kf of 0.005 gives around this level at basal PKC activity levels of 0.1 uM active PKC.
fast: false
reversible: true
type: Reaction

462809
local parameters: 352790
local parameters: 352787
notes: kf*DAG*PLA2_slash_PLA2_minus_Ca_star_-kb*PLA2_slash_DAG_minus_Ca_minus_PLA2_star_
type: KineticLaw

467434
local parameters: 353039
notes: k3*PLCbeta_slash_PLC_minus_Ca_minus_Gq_slash_PLCb_minus_Ca_minus_Gq_slash_PLCb_minus_Ca_minus_Gq_cplx
type: KineticLaw

441494
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

352798
units: 462030
value: 0.0
type: LocalParameter

353033
units: 462030
value: 1.5E-14
type: LocalParameter

462628
stoichiometry: 1.0
species: 439914
type: SpeciesReference

468533
stoichiometry: 1.0
species: 441014
type: SpeciesReference

462140
exponent: -1.0
scale: -6
multipler: 1.0
kind: MOLE
type: SBMLUnit

444893
kinetic law: 465935
product: 465923
product: 465910
reactant: 465898
fast: false
reversible: false
type: Reaction

352970
units: 462030
value: 0.0
type: LocalParameter

447013
kinetic law: 471142
product: 471130
product: 471117
reactant: 471104
fast: false
reversible: false
type: Reaction

463761
stoichiometry: 1.0
species: 441034
type: SpeciesReference

465331
stoichiometry: 1.0
species: 442634
type: SpeciesReference

469124
local parameters: 353110
local parameters: 353107
notes: k1*PP1_slash_I1*PKA_minus_active-k2*PKA_minus_active_slash_PKA_minus_phosph_minus_I1_slash_PKA_minus_phosph_minus_I1_cplx
type: KineticLaw

352797
units: 462030
value: 2.55E-16
type: LocalParameter

443274
notes: ATP is present in all cells between 2 and 10 mM. See Lehninger.
constant: true
boundary condition: true
has only substance units: false
initial concentration: 5000.0
initial amount: NaN
in compartment: 439494
type: Species

353032
units: 462030
value: 6.0E-14
type: LocalParameter

468932
local parameters: 353101
local parameters: 353100
notes: k1*Ras_slash_GDP_minus_Ras*Ras_slash_CaM_minus_GEF-k2*Ras_slash_CaM_minus_GEF_slash_CaM_minus_GEF_minus_act_minus_ras_slash_CaM_minus_GEF_minus_act_minus_ras_cplx
type: KineticLaw

466380
local parameters: 352996
local parameters: 352995
notes: k1*AC_slash_AC2*PKC_minus_active-k2*PKC_minus_active_slash_phosph_minus_AC2_slash_phosph_minus_AC2_cplx
type: KineticLaw

353324
units: 462030
value: 1.5E-14
type: LocalParameter

463448
stoichiometry: 1.0
species: 440474
type: SpeciesReference

467143
stoichiometry: 1.0
species: 440214
type: SpeciesReference

352759
units: 462030
value: 1.5E-15
type: LocalParameter

468654
stoichiometry: 1.0
species: 441054
type: SpeciesReference

463388
local parameters: 352826
local parameters: 352825
notes: kf*G_star_GDP*BetaGamma-kb*Gq_slash_G_minus_GDP
type: KineticLaw

445213
kinetic law: 466720
product: 466708
product: 466696
reactant: 466684
fast: false
reversible: false
type: Reaction

441214
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

465959
stoichiometry: 1.0
species: 443294
type: SpeciesReference

445253
kinetic law: 466816
product: 466804
product: 466792
reactant: 466780
fast: false
reversible: false
type: Reaction

471361
stoichiometry: 1.0
species: 442714
type: SpeciesReference

442234
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

353031
units: 462115
value: 3.78E-15
type: LocalParameter

439483
constant: true
size: 1.0E-18
spatial dimensions: 3.0
type: Compartment

353030
units: 462030
value: 1.5E-14
type: LocalParameter

470740
stoichiometry: 1.0
species: 443354
type: SpeciesReference

440234
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.73
initial amount: NaN
in compartment: 439494
type: Species

353321
units: 462030
value: 6.0E-14
type: LocalParameter

352758
units: 462030
value: 5.2539E-15
type: LocalParameter

443913
kinetic law: 463677
product: 463665
reactant: 463653
reactant: 463641
notes: The rate consts give a total binding affinity of only
fast: false
reversible: true
type: Reaction

464752
stoichiometry: 1.0
species: 442134
type: SpeciesReference

352799
units: 462115
value: 4.499955E-15
type: LocalParameter

466684
stoichiometry: 1.0
species: 440034
type: SpeciesReference

443953
kinetic law: 463809
product: 463797
reactant: 463785
fast: false
reversible: true
type: Reaction

446853
kinetic law: 470752
product: 470740
product: 470728
reactant: 470716
fast: false
reversible: false
type: Reaction

466151
stoichiometry: 1.0
species: 443294
type: SpeciesReference

441254
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

445773
kinetic law: 468111
product: 468099
product: 468087
reactant: 468075
fast: false
reversible: false
type: Reaction

352757
units: 462030
value: 1.90575E-15
type: LocalParameter

463508
stoichiometry: 1.0
species: 440514
type: SpeciesReference

444533
kinetic law: 465102
product: 465090
reactant: 465078
reactant: 465066
fast: false
reversible: true
type: Reaction

352919
units: 462030
value: 1.5E-15
type: LocalParameter

470375
stoichiometry: 1.0
species: 441814
type: SpeciesReference

465006
local parameters: 352930
local parameters: 352929
notes: kf*CaNAB_minus_Ca4*CaM_minus_TR2_minus_Ca2-kb*PP2B_slash_CaMCa2_minus_CANAB
type: KineticLaw

352868
units: 462030
value: 3.75E-16
type: LocalParameter

353180
units: 462115
value: 2.142855E-17
type: LocalParameter

466127
local parameters: 352985
notes: k3*PKC_minus_active_slash_PKC_minus_act_minus_GEF_slash_PKC_minus_act_minus_GEF_cplx
type: KineticLaw

466575
local parameters: 353005
local parameters: 353004
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

467870
local parameters: 353056
local parameters: 353055
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

352961
units: 462115
value: 7.499925E-13
type: LocalParameter

353100
units: 462115
value: 2.97E-16
type: LocalParameter

468341
stoichiometry: 1.0
species: 440974
type: SpeciesReference

353327
units: 462115
value: 7.56E-15
type: LocalParameter

442554
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

467542
stoichiometry: 1.0
species: 440654
type: SpeciesReference

462200
stoichiometry: 1.0
species: 443074
type: SpeciesReference

352974
units: 462030
value: 1.5E-15
type: LocalParameter

439994
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

462881
stoichiometry: 1.0
species: 440094
type: SpeciesReference

468617
stoichiometry: 1.0
species: 441034
type: SpeciesReference

352869
units: 462030
value: 2.50005E-18
type: LocalParameter

466199
stoichiometry: 1.0
species: 442114
type: SpeciesReference

446113
kinetic law: 468932
product: 468920
reactant: 468908
reactant: 468896
notes: Kinetics same as GEF-bg_act-ras
fast: false
reversible: true
type: Reaction

442594
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

462018
exponent: 1.0
scale: -6
multipler: 1.0
kind: MOLE
type: SBMLUnit

443914
kinetic law: 463725
product: 463713
reactant: 463701
reactant: 463689
notes: Assume the binding is fast and limited only by the amount of Ras* available. So kf=kb/[craf-1] If kb is 1/sec, then kf = 1/0.2 uM = 1/(0.2 * 6e5) = 8.3e-6 Later: Raise it by 10 X to 4e-5 From Hallberg et al JBC 269:6 3913-3916 1994, 3% of cellular Raf is complexed with Ras. So we raise kb 4x to 4 This step needed to memb-anchor and activate Raf: Leevers et al Nature 369 411-414 May 16, 2003 Changed Ras and Raf to synaptic levels, an increase of about 2x for each. To maintain the percentage of complexed Raf, reduced the kf by 2.4 fold to 10.
fast: false
reversible: true
type: Reaction

439674
constant: false
boundary condition: false
has only substance units: false
initial concentration: 8.46311111111111E-23
initial amount: NaN
in compartment: 439494
type: Species

445553
kinetic law: 467578
product: 467566
reactant: 467554
reactant: 467542
notes: Rate consts same as for MAPKKtyr.
fast: false
reversible: true
type: Reaction

352973
units: 462115
value: 9.000045E-15
type: LocalParameter

447093
kinetic law: 471337
modifier: 471325
product: 471312
reactant: 471300
fast: false
reversible: false
type: Reaction

464075
stoichiometry: 1.0
species: 441554
type: SpeciesReference

467834
stoichiometry: 1.0
species: 440594
type: SpeciesReference

352866
units: 462030
value: 0.0
type: LocalParameter

471264
stoichiometry: 1.0
species: 442714
type: SpeciesReference

352972
units: 462030
value: 7.5E-15
type: LocalParameter

466648
stoichiometry: 1.0
species: 440014
type: SpeciesReference

446533
kinetic law: 469974
product: 469962
product: 469950
reactant: 469938
fast: false
reversible: false
type: Reaction

353102
units: 462030
value: 3.0E-17
type: LocalParameter

465090
stoichiometry: 1.0
species: 442514
type: SpeciesReference

440394
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

464861
local parameters: 352922
local parameters: 352919
notes: kf*PP1_slash_PP1_minus_I1-kb*PP1_minus_active*PP1_slash_I1
type: KineticLaw

440594
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.5
initial amount: NaN
in compartment: 439494
type: Species

463496
stoichiometry: 1.0
species: 440494
type: SpeciesReference

462737
stoichiometry: 1.0
species: 439934
type: SpeciesReference

464716
stoichiometry: 1.0
species: 442094
type: SpeciesReference

470631
stoichiometry: 1.0
species: 442134
type: SpeciesReference

352867
units: 462115
value: 6.300045E-15
type: LocalParameter

352971
units: 462115
value: 1.08E-12
type: LocalParameter

466043
stoichiometry: 1.0
species: 441074
type: SpeciesReference

353101
units: 462030
value: 1.2E-16
type: LocalParameter

352960
units: 462030
value: 0.0
type: LocalParameter

469889
stoichiometry: 1.0
species: 441834
type: SpeciesReference

352977
units: 462115
value: 4.499955E-16
type: LocalParameter

463593
stoichiometry: 1.0
species: 440434
type: SpeciesReference

352966
units: 462030
value: 1.5E-15
type: LocalParameter

353186
units: 462030
value: 7.5E-16
type: LocalParameter

467651
stoichiometry: 1.0
species: 440754
type: SpeciesReference

352925
units: 462067
value: 1.501254E-11
type: LocalParameter

471709
stoichiometry: 1.0
species: 443034
type: SpeciesReference

352965
units: 462115
value: 1.89E-13
type: LocalParameter

466235
stoichiometry: 1.0
species: 442094
type: SpeciesReference

352978
units: 462030
value: 2.4E-14
type: LocalParameter

439514
constant: true
size: 2.5E-21
spatial dimensions: 3.0
type: Compartment

445593
kinetic law: 467676
product: 467664
reactant: 467651
reactant: 467638
notes: Kinetics are the same as for the craf_1* activity, ie., k1=5.5e-6, k2=0.42, k3 = 0.105 These are basedo n Force et al PNAS USA 91 1270-1274, 1994., but k1 is scaled up 5x (ie., Km is scaled down 5x to the value used here and for craf_1* activity: Km = 0.1591).
fast: false
reversible: true
type: Reaction

441074
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.1
initial amount: NaN
in compartment: 439494
type: Species

470958
stoichiometry: 1.0
species: 442294
type: SpeciesReference

441974
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

471044
local parameters: 353276
notes: k3*PP2A_slash_PP2A_minus_dephosph_minus_PP1_minus_I_star__slash_PP2A_minus_dephosph_minus_PP1_minus_I_star__cplx
type: KineticLaw

467033
stoichiometry: 1.0
species: 440154
type: SpeciesReference

442014
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

439914
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.4
initial amount: NaN
in compartment: 439494
type: Species

446273
kinetic law: 469319
product: 469307
reactant: 469295
reactant: 469283
fast: false
reversible: true
type: Reaction

464608
stoichiometry: 1.0
species: 443074
type: SpeciesReference

465790
stoichiometry: 1.0
species: 440754
type: SpeciesReference

352975
units: 462030
value: 1.5E-13
type: LocalParameter

463653
stoichiometry: 1.0
species: 443234
type: SpeciesReference

465379
stoichiometry: 1.0
species: 442654
type: SpeciesReference

443834
kinetic law: 463388
product: 463376
reactant: 463364
reactant: 463351
notes: kf == kg3 = 1e-5 /cell/sec. As usual, there is no back-reaction kb = 0
fast: false
reversible: true
type: Reaction

352964
units: 462030
value: 1.5E-15
type: LocalParameter

442754
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.02
initial amount: NaN
in compartment: 439494
type: Species

439894
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

353183
units: 462030
value: 3.0E-15
type: LocalParameter

352923
units: 462067
value: 5.399946E-15
type: LocalParameter

442654
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

469853
stoichiometry: 1.0
species: 441794
type: SpeciesReference

464436
stoichiometry: 1.0
species: 441774
type: SpeciesReference

352863
units: 462030
value: 1.5E-15
type: LocalParameter

466744
stoichiometry: 1.0
species: 440054
type: SpeciesReference

463809
local parameters: 352854
local parameters: 352851
notes: kf*Ras_slash_GEF_star_-kb*Ras_slash_inact_minus_GEF
type: KineticLaw

352819
units: 462115
value: 2.520045E-14
type: LocalParameter

352976
units: 462030
value: 1.5E-13
type: LocalParameter

470277
stoichiometry: 1.0
species: 441854
type: SpeciesReference

470522
stoichiometry: 1.0
species: 442054
type: SpeciesReference

443833
kinetic law: 463339
product: 463327
product: 463314
reactant: 463302
notes: kf = kg1 = 0.01/sec, kb = 0. This is the basal exchange of GTP for GDP.
fast: false
reversible: true
type: Reaction

465560
stoichiometry: 1.0
species: 442794
type: SpeciesReference

471117
stoichiometry: 1.0
species: 442254
type: SpeciesReference

352924
units: 462030
value: 1.5E-15
type: LocalParameter

465814
stoichiometry: 1.0
species: 443094
type: SpeciesReference

469659
stoichiometry: 1.0
species: 440234
type: SpeciesReference

352862
units: 462030
value: 1.5E-15
type: LocalParameter

442714
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

353144
units: 461994
value: 97.2222222222222
type: LocalParameter

352818
units: 462030
value: 1.5E-15
type: LocalParameter

471008
stoichiometry: 1.0
species: 442374
type: SpeciesReference

445153
kinetic law: 466575
product: 466563
reactant: 466551
reactant: 466539
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

352929
units: 462115
value: 3.600045E-16
type: LocalParameter

469816
stoichiometry: 1.0
species: 441894
type: SpeciesReference

352755
units: 462115
value: 1.1999745E-17
type: LocalParameter

443854
kinetic law: 463472
product: 463460
reactant: 463448
reactant: 463436
notes: This is the k1-k2 equivalent for enzyme complex formation in the binding of Rec-Glu to Gq. See Fay et al Biochem 30 5066-5075 1991. kf = 5e-5 which is nearly the same as calculated by Fay et al. (4.67e-5) kb = .04 June 1996: Closer reading of Fay et al suggests that kb <= 0.0001, so kf = 1e-8 by detailed balance. This reaction appears to be neglible.
fast: false
reversible: true
type: Reaction

352817
units: 462115
value: 4.499955E-14
type: LocalParameter

465150
local parameters: 352938
local parameters: 352935
notes: kf*PKA_slash_R2C2*cAMP-kb*PKA_slash_R2C2_minus_cAMP
type: KineticLaw

352861
units: 462115
value: 9.000045E-14
type: LocalParameter

440134
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

446493
kinetic law: 469877
product: 469865
product: 469853
reactant: 469840
fast: false
reversible: false
type: Reaction

466428
local parameters: 352997
notes: k3*PKC_minus_active_slash_phosph_minus_AC2_slash_phosph_minus_AC2_cplx
type: KineticLaw

464255
stoichiometry: 1.0
species: 441614
type: SpeciesReference

353189
units: 462115
value: 5.147955E-16
type: LocalParameter

443654
kinetic law: 462665
product: 462653
reactant: 462640
reactant: 462628
notes: Leslie and Channon BBA 1045 (1990) 261-270 fig6 pp267.
fast: false
reversible: true
type: Reaction

440174
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

469767
stoichiometry: 1.0
species: 443314
type: SpeciesReference

440874
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.024
initial amount: NaN
in compartment: 439494
type: Species

352756
units: 462030
value: 1.29522E-14
type: LocalParameter

441894
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

352969
units: 462030
value: 1.5E-16
type: LocalParameter

443853
kinetic law: 463424
product: 463412
reactant: 463400
notes: From Berstein et al JBC 267:12 8081-8088 1992, kcat for GTPase activity of Gq is only 0.8/min
fast: false
reversible: true
type: Reaction

352816
units: 462030
value: 1.5E-15
type: LocalParameter

470861
stoichiometry: 1.0
species: 442274
type: SpeciesReference

469016
stoichiometry: 1.0
species: 441314
type: SpeciesReference

352860
units: 462030
value: 0.0
type: LocalParameter

471421
stoichiometry: 1.0
species: 442914
type: SpeciesReference

441814
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

465524
local parameters: 352960
local parameters: 352959
notes: kf*AC_slash_AC2_star_-kb*AC_slash_AC2
type: KineticLaw

352968
units: 462030
value: 1.5E-15
type: LocalParameter

353330
units: 462030
value: 1.2E-13
type: LocalParameter

352753
units: 462115
value: 9.000045E-16
type: LocalParameter

352979
units: 462030
value: 6.0E-15
type: LocalParameter

353147
units: 462030
value: 8.55E-14
type: LocalParameter

463278
stoichiometry: 1.0
species: 440474
type: SpeciesReference

443054
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

471697
stoichiometry: 1.0
species: 443014
type: SpeciesReference

439814
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

471757
stoichiometry: 1.0
species: 443014
type: SpeciesReference

441294
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

352928
units: 462030
value: 1.5E-15
type: LocalParameter

465499
stoichiometry: 1.0
species: 442774
type: SpeciesReference

352967
units: 462115
value: 1.2499245E-12
type: LocalParameter

439854
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

352754
units: 462030
value: 7.5E-16
type: LocalParameter

470228
stoichiometry: 1.0
species: 441994
type: SpeciesReference

464644
stoichiometry: 1.0
species: 442154
type: SpeciesReference

466343
stoichiometry: 1.0
species: 442814
type: SpeciesReference

462941
stoichiometry: 1.0
species: 443074
type: SpeciesReference

463544
stoichiometry: 1.0
species: 440394
type: SpeciesReference

467254
local parameters: 353032
local parameters: 353031
notes: k1*PIP2*PLCbeta_slash_PLC_minus_Ca-k2*PLCbeta_slash_PLC_minus_Ca_slash_PLC_minus_Ca_slash_PLC_minus_Ca_cplx
type: KineticLaw

462310
local parameters: 352758
local parameters: 352757
notes: kf*PKC_slash_PKC_minus_Ca-kb*PKC_slash_PKC_minus_Ca_minus_memb_star_
type: KineticLaw

444353
kinetic law: 464680
product: 464668
reactant: 464656
reactant: 464644
notes: Use K3 = 21.5 uM here from Stemmer and Klee table 3. kb/kf =21.5 * 6e5 so kf = 7.75e-7, kb = 10
fast: false
reversible: true
type: Reaction

446913
kinetic law: 470897
product: 470885
reactant: 470873
reactant: 470861
notes: PP2A does most of the dephosph of I1 at basal Ca levels. See the review by Cohen in Ann Rev Biochem 1989. For now, lets halve Km. k1 was 3.3e-6, now 6.6e-6
fast: false
reversible: true
type: Reaction

462591
stoichiometry: 1.0
species: 439774
type: SpeciesReference

446053
kinetic law: 468786
product: 468774
product: 468762
reactant: 468750
fast: false
reversible: false
type: Reaction

471080
stoichiometry: 1.0
species: 442414
type: SpeciesReference

353258
units: 462030
value: 5.1E-16
type: LocalParameter

353204
units: 462030
value: 5.25E-16
type: LocalParameter

440114
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

352813
units: 462115
value: 3.78E-15
type: LocalParameter

468389
stoichiometry: 1.0
species: 440934
type: SpeciesReference

463882
local parameters: 352860
local parameters: 352857
notes: kf*Ras_slash_GAP_star_-kb*Ras_slash_GAP
type: KineticLaw

462555
stoichiometry: 1.0
species: 439694
type: SpeciesReference

463737
stoichiometry: 1.0
species: 440374
type: SpeciesReference

468798
stoichiometry: 1.0
species: 441134
type: SpeciesReference

471589
stoichiometry: 1.0
species: 442714
type: SpeciesReference

463122
stoichiometry: 1.0
species: 440414
type: SpeciesReference

462469
local parameters: 352770
local parameters: 352767
notes: kf*PKC_slash_PKC_minus_cytosolic-kb*PKC_slash_PKC_minus_basal_star_
type: KineticLaw

468509
stoichiometry: 1.0
species: 440634
type: SpeciesReference

470058
stoichiometry: 1.0
species: 443334
type: SpeciesReference

352812
units: 462115
value: 0.0
type: LocalParameter

446093
kinetic law: 468884
product: 468871
product: 468858
reactant: 468846
fast: false
reversible: false
type: Reaction

464364
local parameters: 352890
local parameters: 352889
notes: kf*Ca*PLC_g_slash_PLC_G_star_-kb*PLC_g_slash_Ca_dot_PLC_g_star_
type: KineticLaw

464692
stoichiometry: 1.0
species: 442134
type: SpeciesReference

446953
kinetic law: 470996
product: 470983
reactant: 470971
reactant: 470958
notes: k1 changed from 3.3e-6 to 6.6e-6
fast: false
reversible: true
type: Reaction

444133
kinetic law: 464183
product: 464171
reactant: 464159
reactant: 464147
notes: Same rates as Grb2_bind_Sos: Porfiri and McCormick JBC 271:10 pp 5871 1996 show that the binding is not affected by the phosph.
fast: false
reversible: true
type: Reaction

446893
kinetic law: 470848
product: 470836
product: 470824
reactant: 470812
fast: false
reversible: false
type: Reaction

469283
stoichiometry: 1.0
species: 441154
type: SpeciesReference

468172
stoichiometry: 1.0
species: 440914
type: SpeciesReference

463629
local parameters: 352842
local parameters: 352839
notes: kf*Gq_slash_G_minus_GDP*Gq_slash_mGluR-kb*Gq_slash_Rec_minus_Gq
type: KineticLaw

352811
units: 462030
value: 1.995E-17
type: LocalParameter

466007
stoichiometry: 1.0
species: 441174
type: SpeciesReference

470338
stoichiometry: 1.0
species: 441754
type: SpeciesReference

467107
local parameters: 353027
notes: k3*MAPK_star__slash_MAPK_star__minus_feedback_slash_MAPK_star__minus_feedback_cplx
type: KineticLaw

353297
units: 461994
value: 20.1152893440692
type: LocalParameter

465633
stoichiometry: 1.0
species: 443054
type: SpeciesReference

468461
stoichiometry: 1.0
species: 440994
type: SpeciesReference

442274
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.001
initial amount: NaN
in compartment: 439494
type: Species

446753
kinetic law: 470509
product: 470496
reactant: 470484
reactant: 470472
fast: false
reversible: true
type: Reaction

467506
stoichiometry: 1.0
species: 440654
type: SpeciesReference

468184
stoichiometry: 1.0
species: 440654
type: SpeciesReference

446713
kinetic law: 470411
product: 470399
reactant: 470387
reactant: 470375
fast: false
reversible: true
type: Reaction

468232
stoichiometry: 1.0
species: 440934
type: SpeciesReference

469356
stoichiometry: 1.0
species: 441394
type: SpeciesReference

444853
kinetic law: 465838
product: 465826
reactant: 465814
fast: false
reversible: true
type: Reaction

446793
kinetic law: 470607
product: 470594
reactant: 470582
reactant: 470570
notes: From Seki et al ABB 316(2):673-679
fast: false
reversible: true
type: Reaction

352810
units: 462030
value: 1.5E-15
type: LocalParameter

353207
units: 462115
value: 5.147955E-16
type: LocalParameter

462665
local parameters: 352780
local parameters: 352779
notes: kf*PLA2_slash_PLA2_minus_cytosolic*Ca-kb*PLA2_slash_PLA2_minus_Ca_star_
type: KineticLaw

471649
stoichiometry: 1.0
species: 442854
type: SpeciesReference

469926
local parameters: 353174
local parameters: 353171
notes: k1*CaMKII_slash_CaMKII_minus_thr286*CaMKII_slash_tot_autonomous_CaMKII-k2*CaMKII_slash_tot_autonomous_CaMKII_slash_auton_305_slash_auton_305_cplx
type: KineticLaw

466539
stoichiometry: 1.0
species: 443114
type: SpeciesReference

463845
local parameters: 352856
local parameters: 352855
notes: kf*Ras_slash_GTP_minus_Ras-kb*Ras_slash_GDP_minus_Ras
type: KineticLaw

353141
units: 462030
value: 2.1E-14
type: LocalParameter

444173
kinetic law: 464267
product: 464255
reactant: 464243
reactant: 464231
notes: As there are 2 SH3 domains, this reaction could be 2nd order. I have a Kd of 22 uM from peptide binding (Lemmon et al JBC 269:50 pg 31653). However, Chook et al JBC 271:48 pg30472 say it is 0.4uM with purified proteins, so we believe them. They say it is 1:1 binding.
fast: false
reversible: true
type: Reaction

464583
local parameters: 352904
local parameters: 352903
notes: kf*CaM_slash_CaM*Ca^2-kb*CaM_minus_TR2_minus_Ca2
type: KineticLaw

469695
stoichiometry: 1.0
species: 441834
type: SpeciesReference

440494
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

353294
units: 462030
value: 1.05E-14
type: LocalParameter

463170
stoichiometry: 1.0
species: 440394
type: SpeciesReference

444753
kinetic law: 465621
product: 465609
reactant: 465597
reactant: 465584
notes: Half-max 8nM from Tang et al JBC266:13 8595-8603 kb/kf = 8 nM = 4800#/cell so kf = kb * 2.08e-4
fast: false
reversible: true
type: Reaction

470800
local parameters: 353255
local parameters: 353252
notes: k1*PP1_slash_PP1_minus_I1_star_*CaM_po_Ca_pc_n_minus_CaNAB-k2*CaM_po_Ca_pc_n_minus_CaNAB_slash_dephosph_minus_PP1_minus_I_star__slash_dephosph_minus_PP1_minus_I_star__cplx
type: KineticLaw

441574
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

467318
local parameters: 353033
notes: k3*PLCbeta_slash_PLC_minus_Ca_slash_PLC_minus_Ca_slash_PLC_minus_Ca_cplx
type: KineticLaw

353140
units: 462030
value: 3.0E-16
type: LocalParameter

353255
units: 462030
value: 2.04E-15
type: LocalParameter

444793
kinetic law: 465705
product: 465693
reactant: 465681
notes: The rates for this are poorly constrained. In adipocytes (probably a different PDE) the dephosphorylation is complete within 15 min, but there are no intermediate time points so it could be much faster. Identity of phosphatase etc is still unknown.
fast: false
reversible: true
type: Reaction

443474
kinetic law: 462274
product: 462261
reactant: 462248
reactant: 462236
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

442194
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

445513
kinetic law: 467482
product: 467470
reactant: 467458
reactant: 467446
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

466852
stoichiometry: 1.0
species: 440114
type: SpeciesReference

352922
units: 462115
value: 0.0
type: LocalParameter

445633
kinetic law: 467772
product: 467760
reactant: 467748
reactant: 467736
notes: Kinetics are the same as for the craf_1* activity, ie., k1=5.5e-6, k2=0.42, k3 = 0.105 These are basedo n Force et al PNAS USA 91 1270-1274, 1994., but k1 is scaled up 5x (ie., Km is scaled down 5x to the value used here and for craf_1* activity: Km = 0.1591).
fast: false
reversible: true
type: Reaction

445093
kinetic law: 466428
product: 466416
product: 466404
reactant: 466392
fast: false
reversible: false
type: Reaction

353201
units: 462030
value: 2.1E-15
type: LocalParameter

465862
stoichiometry: 1.0
species: 443294
type: SpeciesReference

446213
kinetic law: 469173
product: 469160
product: 469148
reactant: 469136
fast: false
reversible: false
type: Reaction

464812
local parameters: 352918
local parameters: 352917
notes: kf*PP1_slash_I1_star_*PP1_minus_active-kb*PP1_slash_PP1_minus_I1_star_
type: KineticLaw

465451
stoichiometry: 1.0
species: 441374
type: SpeciesReference

353252
units: 462115
value: 5.13E-16
type: LocalParameter

469962
stoichiometry: 1.0
species: 443334
type: SpeciesReference

463339
local parameters: 352824
local parameters: 352823
notes: kf*Gq_slash_G_minus_GDP-kb*G_star_GTP*BetaGamma
type: KineticLaw

464327
stoichiometry: 1.0
species: 443074
type: SpeciesReference

462989
stoichiometry: 1.0
species: 440234
type: SpeciesReference

470167
local parameters: 353195
notes: k3*PP1_minus_active_slash_Deph_minus_thr286_slash_Deph_minus_thr286_cplx
type: KineticLaw

469173
local parameters: 353111
notes: k3*PKA_minus_active_slash_PKA_minus_phosph_minus_I1_slash_PKA_minus_phosph_minus_I1_cplx
type: KineticLaw

465042
stoichiometry: 1.0
species: 442474
type: SpeciesReference

353291
units: 461994
value: 20.0
type: LocalParameter

465705
local parameters: 352970
local parameters: 352969
notes: kf*AC_slash_cAMP_minus_PDE_star_-kb*AC_slash_cAMP_minus_PDE
type: KineticLaw

466948
stoichiometry: 1.0
species: 440174
type: SpeciesReference

462359
stoichiometry: 1.0
species: 439534
type: SpeciesReference

464969
stoichiometry: 1.0
species: 442394
type: SpeciesReference

463230
stoichiometry: 1.0
species: 440314
type: SpeciesReference

470447
stoichiometry: 1.0
species: 441954
type: SpeciesReference

465778
stoichiometry: 1.0
species: 441134
type: SpeciesReference

465211
stoichiometry: 1.0
species: 442574
type: SpeciesReference

466031
local parameters: 352982
notes: k3*PKC_minus_active_slash_PKC_minus_inact_minus_GAP_slash_PKC_minus_inact_minus_GAP_cplx
type: KineticLaw

465850
stoichiometry: 1.0
species: 440554
type: SpeciesReference

441374
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

353243
units: 462115
value: 5.13E-16
type: LocalParameter

439554
constant: false
boundary condition: false
has only substance units: false
initial concentration: 4.91366666666667E-18
initial amount: NaN
in compartment: 439494
type: Species

469247
stoichiometry: 1.0
species: 442934
type: SpeciesReference

464873
stoichiometry: 2.0
species: 443074
type: SpeciesReference

468293
stoichiometry: 1.0
species: 440934
type: SpeciesReference

441334
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

470509
local parameters: 353228
local parameters: 353225
notes: k1*CaMKII_slash_CaMKII_minus_thr286*PP1_minus_active-k2*PP1_minus_active_slash_Deph_thr286b_slash_Deph_thr286b_cplx
type: KineticLaw

442354
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

445373
kinetic law: 467107
product: 467094
product: 467082
reactant: 467070
fast: false
reversible: false
type: Reaction

466708
stoichiometry: 1.0
species: 440014
type: SpeciesReference

447253
kinetic law: 471721
product: 471709
reactant: 471697
reactant: 471685
notes: Max activity ~10umol/min/mg in presence of lots of CaM. Affinity is low, 40 uM. k3 = 10, k2 = 40, k1 = (50/40) / 6e5.
fast: false
reversible: true
type: Reaction

468413
stoichiometry: 1.0
species: 440734
type: SpeciesReference

468063
local parameters: 353065
local parameters: 353064
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

442974
constant: false
boundary condition: false
has only substance units: false
initial concentration: 2.0
initial amount: NaN
in compartment: 439494
type: Species

469707
stoichiometry: 1.0
species: 443314
type: SpeciesReference

464473
stoichiometry: 1.0
species: 441374
type: SpeciesReference

471505
stoichiometry: 1.0
species: 442934
type: SpeciesReference

471469
stoichiometry: 1.0
species: 442894
type: SpeciesReference

462261
stoichiometry: 1.0
species: 439674
type: SpeciesReference

445653
kinetic law: 467821
product: 467809
product: 467797
reactant: 467784
fast: false
reversible: false
type: Reaction

468774
stoichiometry: 1.0
species: 441094
type: SpeciesReference

469489
stoichiometry: 1.0
species: 441454
type: SpeciesReference

469307
stoichiometry: 1.0
species: 441414
type: SpeciesReference

468629
stoichiometry: 1.0
species: 441054
type: SpeciesReference

467626
local parameters: 353045
notes: k3*MAPK_slash_MAPKK_star__slash_MAPKKthr_slash_MAPKKthr_cplx
type: KineticLaw

463302
stoichiometry: 1.0
species: 440434
type: SpeciesReference

445333
kinetic law: 467009
product: 466997
product: 466985
reactant: 466972
fast: false
reversible: false
type: Reaction

467554
stoichiometry: 1.0
species: 440674
type: SpeciesReference

462212
stoichiometry: 1.0
species: 439534
type: SpeciesReference

443614
kinetic law: 462567
product: 462555
reactant: 462542
reactant: 462530
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

465066
stoichiometry: 1.0
species: 441374
type: SpeciesReference

462579
stoichiometry: 1.0
species: 439694
type: SpeciesReference

353339
units: 462030
value: 1.0005E-14
type: LocalParameter

463991
stoichiometry: 1.0
species: 443254
type: SpeciesReference

464087
local parameters: 352874
local parameters: 352873
notes: kf*EGFR_slash_L_dot_EGFR-kb*EGFR_slash_Internal_L_dot_EGFR
type: KineticLaw

353240
units: 462030
value: 1.005E-15
type: LocalParameter

446253
kinetic law: 469271
product: 469259
product: 469247
reactant: 469235
fast: false
reversible: false
type: Reaction

467955
stoichiometry: 1.0
species: 440854
type: SpeciesReference

462857
stoichiometry: 1.0
species: 440134
type: SpeciesReference

464945
stoichiometry: 1.0
species: 442454
type: SpeciesReference

468810
stoichiometry: 1.0
species: 441194
type: SpeciesReference

470046
stoichiometry: 1.0
species: 441794
type: SpeciesReference

466187
stoichiometry: 1.0
species: 439854
type: SpeciesReference

466985
stoichiometry: 1.0
species: 440134
type: SpeciesReference

464003
stoichiometry: 1.0
species: 441454
type: SpeciesReference

468027
stoichiometry: 1.0
species: 440654
type: SpeciesReference

467094
stoichiometry: 1.0
species: 440154
type: SpeciesReference

462371
stoichiometry: 1.0
species: 439774
type: SpeciesReference

463351
stoichiometry: 1.0
species: 440414
type: SpeciesReference

353333
units: 462030
value: 3.0E-14
type: LocalParameter

470776
stoichiometry: 1.0
species: 443354
type: SpeciesReference

353246
units: 462030
value: 2.04E-15
type: LocalParameter

465923
stoichiometry: 1.0
species: 443294
type: SpeciesReference

440274
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

441514
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.5
initial amount: NaN
in compartment: 439494
type: Species

463013
local parameters: 352804
local parameters: 352803
notes: kf*IP3-kb*PLCbeta_slash_Inositol
type: KineticLaw

446973
kinetic law: 471044
product: 471032
product: 471020
reactant: 471008
fast: false
reversible: false
type: Reaction

470496
stoichiometry: 1.0
species: 442054
type: SpeciesReference

353336
units: 462115
value: 3.149955E-16
type: LocalParameter

470668
stoichiometry: 1.0
species: 442274
type: SpeciesReference

467991
stoichiometry: 1.0
species: 440674
type: SpeciesReference

464836
stoichiometry: 1.0
species: 441954
type: SpeciesReference

442474
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

469550
stoichiometry: 1.0
species: 441454
type: SpeciesReference

439494
constant: true
size: 1.5E-15
spatial dimensions: 3.0
type: Compartment

353020
units: 462030
value: 6.0E-14
type: LocalParameter

468920
stoichiometry: 1.0
species: 441274
type: SpeciesReference

467518
stoichiometry: 1.0
species: 440674
type: SpeciesReference

469404
stoichiometry: 1.0
species: 441474
type: SpeciesReference

440954
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

464219
local parameters: 352882
local parameters: 352881
notes: kf*Sos_slash_Sos_star_-kb*Sos_slash_Sos
type: KineticLaw

464195
stoichiometry: 1.0
species: 441634
type: SpeciesReference

464547
stoichiometry: 1.0
species: 442074
type: SpeciesReference

468738
local parameters: 353092
local parameters: 353091
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

467229
stoichiometry: 1.0
species: 440274
type: SpeciesReference

463954
stoichiometry: 1.0
species: 441074
type: SpeciesReference

466453
stoichiometry: 1.0
species: 439934
type: SpeciesReference

446193
kinetic law: 469124
product: 469112
reactant: 469100
reactant: 469088
notes: #s from Bramson et al CRC crit rev Biochem 15:2 93-124. They have a huge list of peptide substrates and I have chosen high-ish rates. These consts give too much PKA activity, so lower Vmax 1/3. Now, k1 = 3e-5, k2 = 36, k3 = 9 (still pretty fast). Also lower Km 1/3 so k1 = 1e-5 Cohen et al FEBS Lett 76:182-86 1977 say rate =30% PKA act on phosphokinase beta.
fast: false
reversible: true
type: Reaction

353021
units: 462030
value: 1.5E-14
type: LocalParameter

464159
stoichiometry: 1.0
species: 441594
type: SpeciesReference

466816
local parameters: 353015
notes: k3*PLA2_slash_DAG_minus_Ca_minus_PLA2_star__slash_kenz_slash_kenz_cplx
type: KineticLaw

440534
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

442434
constant: false
boundary condition: false
has only substance units: false
initial concentration: 1.0
initial amount: NaN
in compartment: 439494
type: Species

464207
stoichiometry: 1.0
species: 441654
type: SpeciesReference

441554
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

468135
stoichiometry: 1.0
species: 440874
type: SpeciesReference

353062
units: 462030
value: 1.8E-15
type: LocalParameter

466636
stoichiometry: 1.0
species: 443114
type: SpeciesReference

352854
units: 462030
value: 0.0
type: LocalParameter

467846
stoichiometry: 1.0
species: 440814
type: SpeciesReference

466079
local parameters: 352984
local parameters: 352983
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

466780
stoichiometry: 1.0
species: 440074
type: SpeciesReference

443214
constant: true
boundary condition: true
has only substance units: false
initial concentration: 10.0
initial amount: NaN
in compartment: 439494
type: Species

442774
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

469877
local parameters: 353168
notes: k3*CaMKII_slash_tot_CaM_CaMKII_slash_CaM_act_286_slash_CaM_act_286_cplx
type: KineticLaw

469514
local parameters: 353137
local parameters: 353134
notes: k1*EGFR_slash_SHC*EGFR_slash_L_dot_EGFR-k2*EGFR_slash_L_dot_EGFR_slash_phosph_Shc_slash_phosph_Shc_cplx
type: KineticLaw

353074
units: 462030
value: 3.6E-14
type: LocalParameter

441154
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.5
initial amount: NaN
in compartment: 439494
type: Species

466600
stoichiometry: 1.0
species: 439774
type: SpeciesReference

353023
units: 462115
value: 2.925045E-15
type: LocalParameter

463918
stoichiometry: 1.0
species: 441254
type: SpeciesReference

352855
units: 462030
value: 1.5E-19
type: LocalParameter

464728
local parameters: 352912
local parameters: 352911
notes: kf*CaM_slash_neurogranin*CaM_slash_CaM-kb*CaM_slash_neurogranin_minus_CaM
type: KineticLaw

465681
stoichiometry: 1.0
species: 442934
type: SpeciesReference

353075
units: 462030
value: 9.0E-15
type: LocalParameter

462701
stoichiometry: 1.0
species: 439974
type: SpeciesReference

467494
stoichiometry: 1.0
species: 440694
type: SpeciesReference

463460
stoichiometry: 1.0
species: 440514
type: SpeciesReference

444593
kinetic law: 465247
product: 465235
reactant: 465223
reactant: 465211
fast: false
reversible: true
type: Reaction

462893
local parameters: 352796
local parameters: 352793
notes: kf*PLA2_slash_PLA2_star_*Ca-kb*PLA2_slash_PLA2_star__minus_Ca
type: KineticLaw

471166
stoichiometry: 1.0
species: 442714
type: SpeciesReference

462482
stoichiometry: 1.0
species: 439774
type: SpeciesReference

443893
kinetic law: 463629
product: 463617
reactant: 463605
reactant: 463593
notes: Lets try out the same kinetics as the Rec-Glu-bind-Gq This is much too forward. We know that the steady-state amount of Rec-Gq should be 40% of the total amount of receptor. This is for a different receptor, still we can try to match the value. kf = 1e-6 and kb = 1 give 0.333:0.8 which is pretty close.
fast: false
reversible: true
type: Reaction

464656
stoichiometry: 1.0
species: 443074
type: SpeciesReference

440454
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.3
initial amount: NaN
in compartment: 439494
type: Species

469441
stoichiometry: 1.0
species: 441734
type: SpeciesReference

467409
stoichiometry: 1.0
species: 440234
type: SpeciesReference

467883
stoichiometry: 1.0
species: 440834
type: SpeciesReference

470094
stoichiometry: 1.0
species: 441954
type: SpeciesReference

445873
kinetic law: 468353
product: 468341
reactant: 468329
reactant: 468317
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

352856
units: 462030
value: 0.0
type: LocalParameter

470387
stoichiometry: 1.0
species: 441954
type: SpeciesReference

440854
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

353065
units: 462030
value: 2.4E-14
type: LocalParameter

353076
units: 462115
value: 2.87415E-15
type: LocalParameter

471721
local parameters: 353348
local parameters: 353345
notes: k1*cAMP*AC_slash_CaM_dot_PDE1-k2*AC_slash_CaM_dot_PDE1_slash_CaM_dot_PDE1_slash_CaM_dot_PDE1_cplx
type: KineticLaw

446453
kinetic law: 469779
product: 469767
product: 469755
reactant: 469743
fast: false
reversible: false
type: Reaction

353063
units: 462030
value: 4.5E-16
type: LocalParameter

445193
kinetic law: 466672
product: 466660
reactant: 466648
reactant: 466636
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

352857
units: 462030
value: 1.5E-16
type: LocalParameter

462006
exponent: -1.0
scale: 0
multipler: 1.0
kind: LITRE
type: SBMLUnit

470118
local parameters: 353192
local parameters: 353189
notes: k1*CaMKII_slash_CaMKII_minus_thr286_star__minus_CaM*PP1_minus_active-k2*PP1_minus_active_slash_Deph_minus_thr286_slash_Deph_minus_thr286_cplx
type: KineticLaw

445833
kinetic law: 468256
product: 468244
reactant: 468232
reactant: 468220
notes: See parent PPhosphatase2A for parms
fast: false
reversible: true
type: Reaction

353064
units: 462115
value: 2.250045E-13
type: LocalParameter

353077
units: 462030
value: 3.6E-14
type: LocalParameter

464764
local parameters: 352916
local parameters: 352913
notes: kf*CaM_slash_neurogranin_star_-kb*CaM_slash_neurogranin
type: KineticLaw

353026
units: 462030
value: 6.0E-14
type: LocalParameter

353078
units: 462030
value: 9.0E-15
type: LocalParameter

353067
units: 462115
value: 2.250045E-13
type: LocalParameter

445034
kinetic law: 466271
product: 466259
reactant: 466247
reactant: 466235
notes: Rates are 60% those of PKC-phosph-neurogranin. See Huang et al ABB 305:2 570-580 1993
fast: false
reversible: true
type: Reaction

444273
kinetic law: 464498
product: 464486
reactant: 464473
reactant: 464460
notes: Affinity is up 1000X. Time to release is about 20 sec, so the kb is OK at 0.1 This makes Kf around 1.6666e-3
fast: false
reversible: true
type: Reaction

353128
units: 462030
value: 1.2E-15
type: LocalParameter

467736
stoichiometry: 1.0
species: 440734
type: SpeciesReference

441314
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

353027
units: 462030
value: 1.5E-14
type: LocalParameter

444813
kinetic law: 465754
product: 465741
reactant: 465729
reactant: 465717
notes: For olf epi PDE1, affinity is 7 nM. Assume same for brain. Reaction should be pretty fast. Assume kb = 5/sec. Then kf = 5 / (0.007 * 6e5) = 1.2e-3
fast: false
reversible: true
type: Reaction

442614
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

353079
units: 462115
value: 2.87415E-15
type: LocalParameter

353066
units: 462030
value: 6.0E-15
type: LocalParameter

465415
stoichiometry: 1.0
species: 442674
type: SpeciesReference

466672
local parameters: 353008
local parameters: 353007
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

463581
local parameters: 352838
local parameters: 352837
notes: kf*Gq_slash_Rec_minus_Glu_minus_Gq-kb*G_star_GTP*BetaGamma*Gq_slash_Rec_minus_Glu
type: KineticLaw

444413
kinetic law: 464812
product: 464800
reactant: 464788
reactant: 464776
notes: K inhib = 1nM from Cohen Ann Rev Bioch 1989, 4 nM from Foukes et al Assume 2 nM. kf /kb = 8.333e-4
fast: false
reversible: true
type: Reaction

465295
local parameters: 352946
local parameters: 352943
notes: kf*cAMP*PKA_slash_R2C2_minus_cAMP3-kb*PKA_slash_R2C2_minus_cAMP4
type: KineticLaw

469136
stoichiometry: 1.0
species: 441334
type: SpeciesReference

353028
units: 462115
value: 2.925045E-14
type: LocalParameter

469598
stoichiometry: 1.0
species: 440234
type: SpeciesReference

468569
stoichiometry: 1.0
species: 440574
type: SpeciesReference

471312
stoichiometry: 1.0
species: 442714
type: SpeciesReference

462152
exponent: -1.0
scale: 0
multipler: 1.0
kind: SECOND
type: SBMLUnit

464111
stoichiometry: 1.0
species: 441534
type: SpeciesReference

353069
units: 462030
value: 6.0E-15
type: LocalParameter

443134
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: 439494
type: Species

462785
stoichiometry: 1.0
species: 439934
type: SpeciesReference

467446
stoichiometry: 1.0
species: 440614
type: SpeciesReference

470558
local parameters: 353231
notes: k3*PP1_minus_active_slash_Deph_thr286b_slash_Deph_thr286b_cplx
type: KineticLaw

463412
stoichiometry: 1.0
species: 440414
type: SpeciesReference

353029
units: 462030
value: 6.0E-14
type: LocalParameter

441734
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

353068
units: 462030
value: 2.4E-14
type: LocalParameter

462103
exponent: -1.0
scale: 0
multipler: 1.0
kind: SECOND
type: SBMLUnit

463797
stoichiometry: 1.0
species: 441074
type: SpeciesReference

465367
stoichiometry: 1.0
species: 441294
type: SpeciesReference

468968
stoichiometry: 1.0
species: 441254
type: SpeciesReference

442394
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

443973
kinetic law: 463845
product: 463833
reactant: 463821
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

468317
stoichiometry: 1.0
species: 440674
type: SpeciesReference

463242
local parameters: 352818
local parameters: 352817
notes: kf*Ca*PLCbeta_slash_PLC_minus_Gq-kb*PLCbeta_slash_PLC_minus_Ca_minus_Gq
type: KineticLaw

470983
stoichiometry: 1.0
species: 442374
type: SpeciesReference

352827
units: 462030
value: 1.995E-17
type: LocalParameter

353019
units: 462115
value: 2.925045E-15
type: LocalParameter

446673
kinetic law: 470313
product: 470301
reactant: 470289
reactant: 470277
notes: See Cohen et al
fast: false
reversible: true
type: Reaction

467331
stoichiometry: 1.0
species: 443214
type: SpeciesReference

439714
constant: false
boundary condition: false
has only substance units: false
initial concentration: 2.51888888888889E-19
initial amount: NaN
in compartment: 439494
type: Species

352932
units: 462030
value: 1.5E-15
type: LocalParameter

462322
stoichiometry: 1.0
species: 439674
type: SpeciesReference

440354
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

469235
stoichiometry: 1.0
species: 441354
type: SpeciesReference

353018
units: 462030
value: 1.8E-13
type: LocalParameter

352826
units: 462030
value: 0.0
type: LocalParameter

352931
units: 462115
value: 3.357045E-15
type: LocalParameter

466563
stoichiometry: 1.0
species: 439994
type: SpeciesReference

465463
stoichiometry: 1.0
species: 442754
type: SpeciesReference

467267
stoichiometry: 1.0
species: 440294
type: SpeciesReference

442934
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

467370
local parameters: 353038
local parameters: 353035
notes: k1*PIP2*PLCbeta_slash_PLC_minus_Ca_minus_Gq-k2*PLCbeta_slash_PLC_minus_Ca_minus_Gq_slash_PLCb_minus_Ca_minus_Gq_slash_PLCb_minus_Ca_minus_Gq_cplx
type: KineticLaw

468678
stoichiometry: 1.0
species: 441034
type: SpeciesReference

353137
units: 462030
value: 1.2E-15
type: LocalParameter

465187
stoichiometry: 1.0
species: 442574
type: SpeciesReference

352934
units: 462030
value: 1.5E-15
type: LocalParameter

442314
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

462749
stoichiometry: 1.0
species: 440014
type: SpeciesReference

444913
kinetic law: 465983
product: 465971
reactant: 465959
reactant: 465947
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

470873
stoichiometry: 1.0
species: 442334
type: SpeciesReference

439594
constant: false
boundary condition: false
has only substance units: false
initial concentration: 1.38955555555556E-17
initial amount: NaN
in compartment: 439494
type: Species

447133
kinetic law: 471433
product: 471421
reactant: 471409
reactant: 471397
notes: Best rates are from Conti et al Biochem 34 7979-7987 1995. Though these are for the Sertoli cell form, it looks like they carry nicely into alternatively spliced brain form. See Sette et al JBC 269:28 18271-18274 Km ~2 uM, Vmax est ~ 10 umol/min/mg for pure form. Brain protein is 93 kD but this was 67. So k3 ~10, k2 ~40, k1 ~4.2e-6
fast: false
reversible: true
type: Reaction

353282
units: 462030
value: 2.04E-16
type: LocalParameter

352933
units: 462115
value: 9.000045E-13
type: LocalParameter

469731
local parameters: 353156
local parameters: 353153
notes: k1*CaMKII_slash_CaMKII_minus_thr286*CaMKII_slash_tot_CaM_CaMKII-k2*CaMKII_slash_tot_CaM_CaMKII_slash_CaM_act_305_slash_CaM_act_305_cplx
type: KineticLaw

466416
stoichiometry: 1.0
species: 443294
type: SpeciesReference

446633
kinetic law: 470216
product: 470203
reactant: 470191
reactant: 470179
fast: false
reversible: true
type: Reaction

470909
stoichiometry: 1.0
species: 442354
type: SpeciesReference

353177
units: 462030
value: 9.0E-15
type: LocalParameter

463857
stoichiometry: 1.0
species: 441174
type: SpeciesReference

445693
kinetic law: 467919
product: 467907
product: 467895
reactant: 467883
fast: false
reversible: false
type: Reaction

465319
stoichiometry: 1.0
species: 441294
type: SpeciesReference

465572
local parameters: 352964
local parameters: 352961
notes: kf*AC_slash_AC2*Gs_minus_alpha-kb*AC_slash_AC2_minus_Gs
type: KineticLaw

352851
units: 462030
value: 1.5E-15
type: LocalParameter

444673
kinetic law: 465439
product: 465427
reactant: 465415
reactant: 465403
notes: This has to be set to zero for matching the expts in vitro. In vivo we need to consider the inhibition though. kf = 1e-5 kb = 1
fast: false
reversible: true
type: Reaction

466527
local parameters: 353003
notes: k3*PLA2_slash_PLA2_minus_Ca_star__slash_kenz_slash_kenz_cplx
type: KineticLaw

440574
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

353131
units: 462030
value: 3.0E-16
type: LocalParameter

470301
stoichiometry: 1.0
species: 442014
type: SpeciesReference

353171
units: 462115
value: 2.571345E-16
type: LocalParameter

467155
local parameters: 353029
local parameters: 353028
notes: k1*Sos_slash_Sos*MAPK_star_-k2*MAPK_star__slash_phosph_Sos_slash_phosph_Sos_cplx
type: KineticLaw

442074
constant: false
boundary condition: false
has only substance units: false
initial concentration: 20.0
initial amount: NaN
in compartment: 439494
type: Species

445753
kinetic law: 468063
product: 468051
reactant: 468039
reactant: 468027
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

352785
units: 462115
value: 1.799955E-17
type: LocalParameter

462408
stoichiometry: 1.0
species: 439714
type: SpeciesReference

352890
units: 462030
value: 1.5E-14
type: LocalParameter

446333
kinetic law: 469465
product: 469453
product: 469441
reactant: 469429
fast: false
reversible: false
type: Reaction

463641
stoichiometry: 1.0
species: 440494
type: SpeciesReference

352850
units: 462030
value: 1.5E-15
type: LocalParameter

467119
stoichiometry: 1.0
species: 441654
type: SpeciesReference

470619
stoichiometry: 1.0
species: 442194
type: SpeciesReference

464596
stoichiometry: 1.0
species: 442174
type: SpeciesReference

465621
local parameters: 352966
local parameters: 352965
notes: kf*Gs_minus_alpha*AC_slash_AC1-kb*AC_slash_AC1_minus_Gs
type: KineticLaw

353285
units: 462030
value: 5.1E-17
type: LocalParameter

466490
stoichiometry: 1.0
species: 439954
type: SpeciesReference

440914
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

444633
kinetic law: 465343
product: 465331
product: 465319
reactant: 465307
notes: This has to be fast, as the activation of PKA by cAMP is also fast. kf was 10
fast: false
reversible: true
type: Reaction

467943
stoichiometry: 1.0
species: 440814
type: SpeciesReference

352891
units: 462030
value: 7.5E-17
type: LocalParameter

467305
stoichiometry: 1.0
species: 440274
type: SpeciesReference

445713
kinetic law: 467967
product: 467955
reactant: 467943
reactant: 467931
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

352786
units: 462030
value: 1.5E-16
type: LocalParameter

469295
stoichiometry: 1.0
species: 441394
type: SpeciesReference

464993
stoichiometry: 1.0
species: 442494
type: SpeciesReference

444973
kinetic law: 466127
product: 466115
product: 466103
reactant: 466091
fast: false
reversible: false
type: Reaction

443594
kinetic law: 462518
product: 462506
reactant: 462494
reactant: 462482
notes: Raise kf from 1.667e-10 to 2e-10 to get better match to data.
fast: false
reversible: true
type: Reaction

440994
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

470945
local parameters: 353267
notes: k3*PP2A_slash_PP2A_minus_dephosph_minus_I1_slash_PP2A_minus_dephosph_minus_I1_cplx
type: KineticLaw

353174
units: 462030
value: 3.6E-14
type: LocalParameter

352892
units: 462030
value: 0.0
type: LocalParameter

352930
units: 462030
value: 1.5E-15
type: LocalParameter

352787
units: 462115
value: 4.499955E-18
type: LocalParameter

444053
kinetic law: 464015
product: 464003
reactant: 463991
reactant: 463979
notes: Affinity of EGFR for EGF is complex: depends on [EGFR]. We\'ll assume fixed [EGFR] and use exptal affinity ~20 nM (see Sherrill and Kyte Biochem 1996 35 5705-5718, Berkers et al JBC 266:2 922-927 1991, Sorokin et al JBC 269:13 9752-9759 1994). Tau =~2 min (Davis et al JBC 263:11 5373-5379 1988) or Berkers Kass = 6.2e5/M/sec, Kdiss=3.5e-4/sec. Sherrill and Kyte have Hill Coeff=1.7
fast: false
reversible: true
type: Reaction

463701
stoichiometry: 1.0
species: 441134
type: SpeciesReference

353134
units: 462115
value: 1.799955E-15
type: LocalParameter

471056
stoichiometry: 1.0
species: 442274
type: SpeciesReference

467664
stoichiometry: 1.0
species: 440774
type: SpeciesReference

444013
kinetic law: 463930
product: 463918
reactant: 463906
reactant: 463894
notes: We have no numbers for this. It is probably between the two extremes represented by the CaMKII phosph states, and I have used guesses based on this. kf=1e-4 kb=1 The reaction is based on Farnsworth et al Nature 376 524-527 1995
fast: false
reversible: true
type: Reaction

467045
stoichiometry: 1.0
species: 440194
type: SpeciesReference

470484
stoichiometry: 1.0
species: 441954
type: SpeciesReference

443554
kinetic law: 462432
product: 462420
reactant: 462408
notes: Assume slowish too. Schaechter and Benowitz
fast: false
reversible: true
type: Reaction

471397
stoichiometry: 1.0
species: 442714
type: SpeciesReference

465741
stoichiometry: 1.0
species: 443014
type: SpeciesReference

352893
units: 462115
value: 7.499925E-14
type: LocalParameter

353071
units: 462115
value: 2.87415E-15
type: LocalParameter

442534
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.5
initial amount: NaN
in compartment: 439494
type: Species

466247
stoichiometry: 1.0
species: 443294
type: SpeciesReference

441914
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

462977
local parameters: 352802
local parameters: 352799
notes: kf*Ca*PLCbeta_slash_PLC-kb*PLCbeta_slash_PLC_minus_Ca
type: KineticLaw

463532
stoichiometry: 1.0
species: 440514
type: SpeciesReference

443713
kinetic law: 462845
product: 462833
reactant: 462821
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

469185
stoichiometry: 1.0
species: 442894
type: SpeciesReference

446033
kinetic law: 468738
product: 468726
reactant: 468714
reactant: 468702
notes: Kinetics same as GEF-bg-act-ras
fast: false
reversible: true
type: Reaction

470155
stoichiometry: 1.0
species: 441954
type: SpeciesReference

441194
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.01
initial amount: NaN
in compartment: 439494
type: Species

352781
units: 462115
value: 1.799955E-18
type: LocalParameter

462055
exponent: -1.0
scale: 0
multipler: 1.0
kind: SECOND
type: SBMLUnit

464909
local parameters: 352924
local parameters: 352923
notes: kf*Ca^2*PP2B_slash_CaNAB_minus_Ca2-kb*CaNAB_minus_Ca4
type: KineticLaw

469974
local parameters: 353177
notes: k3*CaMKII_slash_tot_autonomous_CaMKII_slash_auton_305_slash_auton_305_cplx
type: KineticLaw

464315
local parameters: 352888
local parameters: 352885
notes: kf*PLC_g_slash_PLC_g*Ca-kb*PLC_g_slash_Ca_dot_PLC_g
type: KineticLaw

353288
units: 462030
value: 2.7E-14
type: LocalParameter

467009
local parameters: 353021
notes: k3*MAPK_star__slash_MAPK_star__slash_MAPK_star__cplx
type: KineticLaw

445433
kinetic law: 467254
product: 467242
reactant: 467229
reactant: 467217
notes: From Sternweis et al Phil Trans R Soc Lond 1992, also matched by Homma et al. k1 = 1.5e-5, now 4.2e-6 k2 = 70/sec; now 40/sec k3 = 17.5/sec; now 10/sec Note that the wording in Sternweis et al is ambiguous re the Km.
fast: false
reversible: true
type: Reaction

466936
stoichiometry: 1.0
species: 440154
type: SpeciesReference

446353
kinetic law: 469514
product: 469502
reactant: 469489
reactant: 469477
notes: Rates from Okada et al JBC 270:35 pp 20737 1995 Km = 0.70 to 0.85 uM, Vmax = 4.4 to 5.0 pmol/min. Unfortunately the amount of enzyme is not known, the prep is only partially purified. Time course of phosph is max within 30 sec, falls back within 20 min. Ref: Sasaoka et al JBC 269:51 32621 1994. Use k3 = 0.1 based on this tau.
fast: false
reversible: true
type: Reaction

353342
units: 462030
value: 2.5005E-15
type: LocalParameter

440414
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

465030
stoichiometry: 1.0
species: 442394
type: SpeciesReference

466888
stoichiometry: 1.0
species: 439774
type: SpeciesReference

465971
stoichiometry: 1.0
species: 439814
type: SpeciesReference

470728
stoichiometry: 1.0
species: 442254
type: SpeciesReference

352939
units: 462115
value: 8.1E-14
type: LocalParameter

352896
units: 462030
value: 7.5E-15
type: LocalParameter

440814
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

445473
kinetic law: 467370
product: 467357
reactant: 467344
reactant: 467331
notes: From Sternweis et al, Phil Trans R Soc Lond 1992, and the values from other refs eg Homma et al JBC 263(14) pp6592 1988 match. k1 = 5e-5/sec k2 = 240/sec; now 120/sec k3 = 60/sec; now 30/sec Note that the wording in Sternweis et al is ambiguous wr. to the Km for Gq vs non-Gq states of PLC. K1 is still a bit too low. Raise to 7e-5 9 Jun 1996: k1 was 0.0002, changed to 5e-5
fast: false
reversible: true
type: Reaction

470594
stoichiometry: 1.0
species: 442194
type: SpeciesReference

446413
product: 469659
fast: false
product: 469647
reversible: false
modifier: 469671
type: Reaction
reactant: 469635
kinetic law: 469683
notes: Mainly Homma et al JBC 263:14 1988 pp 6592, but these parms are the Ca-stimulated form. It is not clear whether the enzyme is activated by tyrosine phosphorylation at this point or not. Wahl et al JBC 267:15 10447-10456 1992 say that this has 7X higher affinity for substrate than control.

469028
local parameters: 353104
local parameters: 353103
notes: k1*Ras_slash_inact_minus_GEF*PKA_minus_active-k2*PKA_minus_active_slash_PKA_minus_phosph_minus_GEF_slash_PKA_minus_phosph_minus_GEF_cplx
type: KineticLaw

467772
local parameters: 353053
local parameters: 353052
notes: k1*MAPK_slash_MAPKK_minus_ser*MAPK_slash_Raf_minus_GTP_minus_Ras-k2*MAPK_slash_Raf_minus_GTP_minus_Ras_slash_Raf_minus_GTP_minus_Ras_dot_2_slash_Raf_minus_GTP_minus_Ras_dot_2_cplx
type: KineticLaw

470836
stoichiometry: 1.0
species: 443354
type: SpeciesReference

469779
local parameters: 353159
notes: k3*CaMKII_slash_tot_CaM_CaMKII_slash_CaM_act_305_slash_CaM_act_305_cplx
type: KineticLaw

441114
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

447033
kinetic law: 471191
modifier: 471178
product: 471166
reactant: 471154
fast: false
reversible: false
type: Reaction

464267
local parameters: 352884
local parameters: 352883
notes: kf*Sos_slash_Grb2*Sos_slash_Sos-kb*Sos_slash_Sos_dot_Grb2
type: KineticLaw

442134
constant: false
boundary condition: false
has only substance units: false
initial concentration: 10.0
initial amount: NaN
in compartment: 439494
type: Species

442834
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

442874
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

352897
units: 462115
value: 1.500255E-12
type: LocalParameter

466356
stoichiometry: 1.0
species: 443294
type: SpeciesReference

353237
units: 462030
value: 4.005E-15
type: LocalParameter

443714
kinetic law: 462893
product: 462881
reactant: 462869
reactant: 462857
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

465259
stoichiometry: 1.0
species: 442714
type: SpeciesReference

464800
stoichiometry: 1.0
species: 442294
type: SpeciesReference

465898
stoichiometry: 1.0
species: 439794
type: SpeciesReference

352784
units: 462030
value: 7.5E-16
type: LocalParameter

439774
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

466864
local parameters: 353017
local parameters: 353016
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

469828
local parameters: 353165
local parameters: 353162
notes: k1*CaMKII_slash_CaMKII_minus_CaM*CaMKII_slash_tot_CaM_CaMKII-k2*CaMKII_slash_tot_CaM_CaMKII_slash_CaM_act_286_slash_CaM_act_286_cplx
type: KineticLaw

446833
kinetic law: 470704
product: 470692
reactant: 470680
reactant: 470668
fast: false
reversible: true
type: Reaction

352823
units: 462030
value: 1.5E-19
type: LocalParameter

441774
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

469344
stoichiometry: 1.0
species: 441134
type: SpeciesReference

469623
local parameters: 353144
local parameters: 353141
notes: kcat*PLC_g_slash_Ca_dot_PLC_g*PIP2/(Km+PIP2)
type: KineticLaw

465669
local parameters: 352968
local parameters: 352967
notes: kf*Gs_minus_alpha*AC_slash_AC2_star_-kb*AC_slash_AC2_star__minus_Gs
type: KineticLaw

465102
local parameters: 352934
local parameters: 352933
notes: kf*CaM_minus_Ca4*CaNAB_minus_Ca4-kb*PP2B_slash_CaMCa4_minus_CaNAB
type: KineticLaw

440754
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

352898
units: 462030
value: 1.5E-16
type: LocalParameter

465802
local parameters: 352974
local parameters: 352973
notes: kf*MAPK_slash_craf_minus_1*Ras_slash_GTP_minus_Ras-kb*MAPK_slash_Raf_minus_GTP_minus_Ras
type: KineticLaw

468896
stoichiometry: 1.0
species: 441154
type: SpeciesReference

470265
local parameters: 353204
notes: k3*PP1_minus_active_slash_Deph_minus_thr305_slash_Deph_minus_thr305_cplx
type: KineticLaw

445113
kinetic law: 466478
product: 466465
reactant: 466453
reactant: 466441
notes: 10 x raise oct22 12 x oct 24, set k2 = 4 * k3
fast: false
reversible: true
type: Reaction

462432
local parameters: 352766
local parameters: 352765
notes: kf*PKC_slash_PKC_minus_DAG_minus_AA-kb*PKC_slash_PKC_minus_DAG_minus_AA_star_
type: KineticLaw

468208
local parameters: 353069
notes: k3*MKP_minus_1_slash_MKP1_minus_thr_minus_deph_slash_MKP1_minus_thr_minus_deph_cplx
type: KineticLaw

441674
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.82
initial amount: NaN
in compartment: 439494
type: Species

469938
stoichiometry: 1.0
species: 441914
type: SpeciesReference

462677
stoichiometry: 1.0
species: 443134
type: SpeciesReference

464424
stoichiometry: 1.0
species: 441754
type: SpeciesReference

443773
kinetic law: 463049
product: 463037
reactant: 463025
notes: These rates are the same as for degrading IP3, but I am sure that they could be improved. Lets double kf to 0.2, since the amount of DAG in the cell should be <= 1uM. Need to double it again, for the same reason. kf now 0.5 27 June 1996 kf is now 0.02 to get 50 sec time course 30 Aug 1997: Raised kf to 0.11 to accomodate PLC_gamma 27 Mar 1998: kf now 0.15 for PLC_gamma
fast: false
reversible: true
type: Reaction

440694
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

352935
units: 462115
value: 8.1E-14
type: LocalParameter

352822
units: 462030
value: 1.5E-14
type: LocalParameter

352899
units: 462030
value: 4.5E-18
type: LocalParameter

463689
stoichiometry: 1.0
species: 440574
type: SpeciesReference

440794
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

466319
stoichiometry: 1.0
species: 443294
type: SpeciesReference

468244
stoichiometry: 1.0
species: 440954
type: SpeciesReference

442694
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

471613
stoichiometry: 1.0
species: 442994
type: SpeciesReference

443774
kinetic law: 463098
product: 463086
reactant: 463074
reactant: 463062
notes: Affinity for Gq is > 20 nM (Smrcka et al Science251 804-807 1991) so [Gq].kf = kb so 40nM * 6e5 = kb/kf = 24e3 so kf = 4.2e-5, kb =1
fast: false
reversible: true
type: Reaction

463749
stoichiometry: 1.0
species: 441074
type: SpeciesReference

466295
stoichiometry: 1.0
species: 442074
type: SpeciesReference

440054
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

352825
units: 462115
value: 9.000045E-15
type: LocalParameter

352938
units: 462030
value: 4.95E-14
type: LocalParameter

471541
stoichiometry: 1.0
species: 442954
type: SpeciesReference

444233
kinetic law: 464400
product: 464388
reactant: 464376
fast: false
reversible: true
type: Reaction

352780
units: 462030
value: 1.5E-16
type: LocalParameter

464376
stoichiometry: 1.0
species: 441734
type: SpeciesReference

440094
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

462917
stoichiometry: 1.0
species: 439914
type: SpeciesReference

468858
stoichiometry: 1.0
species: 441154
type: SpeciesReference

469076
local parameters: 353105
notes: k3*PKA_minus_active_slash_PKA_minus_phosph_minus_GEF_slash_PKA_minus_phosph_minus_GEF_cplx
type: KineticLaw

352824
units: 462115
value: 0.0
type: LocalParameter

463098
local parameters: 352810
local parameters: 352807
notes: kf*G_star_GTP*PLCbeta_slash_PLC_minus_Ca-kb*PLCbeta_slash_PLC_minus_Ca_minus_Gq
type: KineticLaw

463134
stoichiometry: 1.0
species: 440274
type: SpeciesReference

440014
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

443174
constant: true
boundary condition: true
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

471577
local parameters: 353333
notes: k3*AC_slash_cAMP_minus_PDE_star__slash_PDE_star__slash_PDE_star__cplx
type: KineticLaw

442514
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

471517
stoichiometry: 1.0
species: 442954
type: SpeciesReference

441474
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

447213
kinetic law: 471625
product: 471613
reactant: 471601
reactant: 471589
notes: Rate is 1/6 of the CaM stim form. We\'ll just reduce all lf k1, k2, k3 so that the Vmax goes down 1/6.
fast: false
reversible: true
type: Reaction

463049
local parameters: 352806
local parameters: 352805
notes: kf*DAG-kb*PLCbeta_slash_PC
type: KineticLaw

352990
units: 462030
value: 3.51E-15
type: LocalParameter

470351
stoichiometry: 1.0
species: 441954
type: SpeciesReference

467638
stoichiometry: 1.0
species: 440594
type: SpeciesReference

463314
stoichiometry: 1.0
species: 440394
type: SpeciesReference

465729
stoichiometry: 1.0
species: 441374
type: SpeciesReference

464460
stoichiometry: 1.0
species: 441834
type: SpeciesReference

471457
stoichiometry: 1.0
species: 442854
type: SpeciesReference

468786
local parameters: 353093
notes: k3*Ras_slash_GEF_star__slash_GEF_star__minus_act_minus_ras_slash_GEF_star__minus_act_minus_ras_cplx
type: KineticLaw

443294
constant: false
boundary condition: true
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

462567
local parameters: 352776
local parameters: 352773
notes: kf*PKC_slash_PKC_minus_cytosolic*DAG-kb*PKC_slash_PKC_minus_DAG
type: KineticLaw

463894
stoichiometry: 1.0
species: 441074
type: SpeciesReference

462224
local parameters: 352754
local parameters: 352753
notes: kf*PKC_slash_PKC_minus_cytosolic*Ca-kb*PKC_slash_PKC_minus_Ca
type: KineticLaw

467566
stoichiometry: 1.0
species: 440714
type: SpeciesReference

465078
stoichiometry: 1.0
species: 442394
type: SpeciesReference

471130
stoichiometry: 1.0
species: 442394
type: SpeciesReference

464099
stoichiometry: 1.0
species: 441614
type: SpeciesReference

444113
kinetic law: 464135
product: 464123
reactant: 464111
reactant: 464099
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

462274
local parameters: 352756
local parameters: 352755
notes: kf*DAG*PKC_slash_PKC_minus_Ca-kb*PKC_slash_PKC_minus_Ca_minus_DAG
type: KineticLaw

353059
units: 462115
value: 1.41426E-14
type: LocalParameter

465766
stoichiometry: 1.0
species: 440554
type: SpeciesReference

470435
stoichiometry: 1.0
species: 441854
type: SpeciesReference

469259
stoichiometry: 1.0
species: 441294
type: SpeciesReference

464885
stoichiometry: 1.0
species: 442454
type: SpeciesReference

353231
units: 462030
value: 5.25E-16
type: LocalParameter

443933
kinetic law: 463773
product: 463761
reactant: 463749
reactant: 463737
notes: SoS/GEF is present at 50 nM ie 3e4/cell. BetaGamma maxes out at 9e4. Assume we have 1/3 of the GEF active when the BetaGamma is 1.5e4. so 1e4 * kb = 2e4 * 1.5e4 * kf, so kf/kb = 3e-5. The rate of this equil should be reasonably fast, say 1/sec
fast: false
reversible: true
type: Reaction

443314
constant: false
boundary condition: true
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

440674
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

353309
units: 461994
value: 20.0
type: LocalParameter

441054
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

446133
kinetic law: 468980
product: 468968
product: 468956
reactant: 468944
fast: false
reversible: false
type: Reaction

443354
constant: false
boundary condition: true
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

441654
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.1
initial amount: NaN
in compartment: 439494
type: Species

440634
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

468051
stoichiometry: 1.0
species: 440894
type: SpeciesReference

446773
kinetic law: 470558
product: 470546
product: 470534
reactant: 470522
fast: false
reversible: false
type: Reaction

471661
stoichiometry: 1.0
species: 442974
type: SpeciesReference

440314
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

463364
stoichiometry: 1.0
species: 440374
type: SpeciesReference

463001
stoichiometry: 1.0
species: 443174
type: SpeciesReference

439654
constant: false
boundary condition: false
has only substance units: false
initial concentration: 1.81333333333333E-17
initial amount: NaN
in compartment: 439494
type: Species

353348
units: 462030
value: 6.0E-14
type: LocalParameter

444933
kinetic law: 466031
product: 466019
product: 466007
reactant: 465995
fast: false
reversible: false
type: Reaction

469416
local parameters: 353128
local parameters: 353125
notes: k1*PLC_g_slash_Ca_dot_PLC_g*EGFR_slash_L_dot_EGFR-k2*EGFR_slash_L_dot_EGFR_slash_phosph_PLC_g_slash_phosph_PLC_g_cplx
type: KineticLaw

464559
stoichiometry: 2.0
species: 443074
type: SpeciesReference

442894
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.45
initial amount: NaN
in compartment: 439494
type: Species

439754
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

469562
local parameters: 353140
notes: k3*EGFR_slash_L_dot_EGFR_slash_phosph_Shc_slash_phosph_Shc_cplx
type: KineticLaw

441414
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

471409
stoichiometry: 1.0
species: 442894
type: SpeciesReference

465138
stoichiometry: 1.0
species: 442554
type: SpeciesReference

442574
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

466441
stoichiometry: 1.0
species: 443114
type: SpeciesReference

463942
stoichiometry: 1.0
species: 441234
type: SpeciesReference

468485
stoichiometry: 1.0
species: 440934
type: SpeciesReference

471493
stoichiometry: 1.0
species: 442714
type: SpeciesReference

443074
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.08
initial amount: NaN
in compartment: 439494
type: Species

439694
constant: false
boundary condition: false
has only substance units: false
initial concentration: 1.161E-16
initial amount: NaN
in compartment: 439494
type: Species

466828
stoichiometry: 1.0
species: 443114
type: SpeciesReference

469040
stoichiometry: 1.0
species: 441314
type: SpeciesReference

467700
stoichiometry: 1.0
species: 440734
type: SpeciesReference

467967
local parameters: 353062
local parameters: 353059
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

471770
local parameters: 353351
notes: k3*AC_slash_CaM_dot_PDE1_slash_CaM_dot_PDE1_slash_CaM_dot_PDE1_cplx
type: KineticLaw

464957
local parameters: 352928
local parameters: 352925
notes: kf*PP2B_slash_CaNAB*Ca^2-kb*PP2B_slash_CaNAB_minus_Ca2
type: KineticLaw

470034
stoichiometry: 1.0
species: 441934
type: SpeciesReference

462869
stoichiometry: 1.0
species: 443074
type: SpeciesReference

468039
stoichiometry: 1.0
species: 440874
type: SpeciesReference

463206
stoichiometry: 1.0
species: 443074
type: SpeciesReference

462383
stoichiometry: 1.0
species: 439574
type: SpeciesReference

466175
local parameters: 352990
local parameters: 352987
notes: k1*CaM_slash_neurogranin*PKC_minus_active-k2*PKC_minus_active_slash_PKC_minus_phosph_minus_neurogranin_slash_PKC_minus_phosph_minus_neurogranin_cplx
type: KineticLaw

464015
local parameters: 352868
local parameters: 352867
notes: kf*EGFR_slash_EGFR*EGFR_slash_EGF-kb*EGFR_slash_L_dot_EGFR
type: KineticLaw

445293
kinetic law: 466912
product: 466900
product: 466888
reactant: 466876
fast: false
reversible: false
type: Reaction

470764
stoichiometry: 1.0
species: 442294
type: SpeciesReference

469901
stoichiometry: 1.0
species: 443334
type: SpeciesReference

464849
stoichiometry: 1.0
species: 442254
type: SpeciesReference

353345
units: 462115
value: 1.89E-15
type: LocalParameter

444733
kinetic law: 465572
product: 465560
reactant: 465548
reactant: 465536
notes: Half-max at around 3nM = kb/kf from fig 5 in Feinstein et al PNAS USA 88 10173-10177 1991 kf = kb/1800 = 5.56e-4 kb Ofer\'s thesis data indicates it is more like 2 nM. kf = kb/1200 = 8.33e-4
fast: false
reversible: true
type: Reaction

465935
local parameters: 352979
notes: k3*PKC_minus_active_slash_PKC_minus_act_minus_raf_slash_PKC_minus_act_minus_raf_cplx
type: KineticLaw

443494
kinetic law: 462310
product: 462298
reactant: 462286
fast: false
reversible: true
type: Reaction

443993
kinetic law: 463882
product: 463870
reactant: 463857
notes: Assume a reasonably good rate for dephosphorylating it, 1/sec
fast: false
reversible: true
type: Reaction

444333
kinetic law: 464632
product: 464620
reactant: 464608
reactant: 464596
notes: K3 = 21.5, K4 = 2.8. Assuming that the K4 step happens first, we get kb/kf = 2.8 uM = 1.68e6 so kf =6e-6 assuming kb = 10
fast: false
reversible: true
type: Reaction

353306
units: 462030
value: 2.7E-14
type: LocalParameter

353234
units: 462115
value: 5.004045E-16
type: LocalParameter

466972
stoichiometry: 1.0
species: 440174
type: SpeciesReference

469453
stoichiometry: 1.0
species: 441454
type: SpeciesReference

467895
stoichiometry: 1.0
species: 440734
type: SpeciesReference

353303
units: 461994
value: 20.0
type: LocalParameter

470082
stoichiometry: 1.0
species: 441794
type: SpeciesReference

466660
stoichiometry: 1.0
species: 440034
type: SpeciesReference

462494
stoichiometry: 1.0
species: 439734
type: SpeciesReference

446593
kinetic law: 470118
product: 470106
reactant: 470094
reactant: 470082
notes: The rates are from Stralfors et al Eur J Biochem 149 295-303 giving Vmax = 5.7 umol/min giving k3 = 3.5/sec and k2 = 14. Foulkes et al Eur J Biochem 132 309-313 1983 give Km = 5.1 uM so k1 becomes 5.72e-6 Simonelli 1984 (Grad Thesis, CUNY) showed that other substrates are about 1/10 rate of phosphorylase a, so we reduce k1,k2,k3 by 10 to 5.72e-7, 1.4, 0.35
fast: false
reversible: true
type: Reaction

353052
units: 462115
value: 1.41426E-14
type: LocalParameter

464668
stoichiometry: 1.0
species: 441374
type: SpeciesReference

465391
local parameters: 352952
local parameters: 352949
notes: kf*PKA_slash_R2C_minus_cAMP4-kb*PKA_minus_active*PKA_slash_R2_minus_cAMP4
type: KineticLaw

353053
units: 462030
value: 1.8E-15
type: LocalParameter

467590
stoichiometry: 1.0
species: 440714
type: SpeciesReference

353088
units: 462115
value: 2.97E-16
type: LocalParameter

444493
kinetic law: 465006
product: 464993
reactant: 464981
reactant: 464969
notes: Disabled. See notes for PP2B7.g
fast: false
reversible: true
type: Reaction

466103
stoichiometry: 1.0
species: 441094
type: SpeciesReference

470399
stoichiometry: 1.0
species: 442034
type: SpeciesReference

352844
units: 462030
value: 1.5E-17
type: LocalParameter

352997
units: 462030
value: 6.0E-15
type: LocalParameter

471733
stoichiometry: 1.0
species: 443034
type: SpeciesReference

464051
local parameters: 352872
local parameters: 352869
notes: kf*EGFR_slash_SHC_star_-kb*EGFR_slash_SHC
type: KineticLaw

353051
units: 462030
value: 4.5E-16
type: LocalParameter

353089
units: 462030
value: 1.2E-16
type: LocalParameter

352845
units: 462115
value: 1.499985E-14
type: LocalParameter

470106
stoichiometry: 1.0
species: 441974
type: SpeciesReference

439934
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

465693
stoichiometry: 1.0
species: 442894
type: SpeciesReference

470692
stoichiometry: 1.0
species: 442214
type: SpeciesReference

468148
stoichiometry: 1.0
species: 440914
type: SpeciesReference

353050
units: 462030
value: 1.8E-15
type: LocalParameter

466624
local parameters: 353006
notes: k3*PLA2_slash_PIP2_minus_PLA2_star__slash_kenz_slash_kenz_cplx
type: KineticLaw

352996
units: 462030
value: 2.4E-14
type: LocalParameter

440254
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.8
initial amount: NaN
in compartment: 439494
type: Species

445573
kinetic law: 467626
product: 467614
product: 467602
reactant: 467590
fast: false
reversible: false
type: Reaction

353086
units: 462030
value: 3.6E-14
type: LocalParameter

445273
kinetic law: 466864
product: 466852
reactant: 466840
reactant: 466828
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

442254
constant: false
boundary condition: false
has only substance units: false
initial concentration: 1.8
initial amount: NaN
in compartment: 439494
type: Species

444513
kinetic law: 465054
product: 465042
reactant: 465030
reactant: 465018
fast: false
reversible: true
type: Reaction

468099
stoichiometry: 1.0
species: 440874
type: SpeciesReference

352842
units: 462030
value: 1.5E-15
type: LocalParameter

471288
local parameters: 353303
local parameters: 353300
notes: kcat*AC_slash_AC2_minus_Gs*AC_slash_ATP/(Km+AC_slash_ATP)
type: KineticLaw

467858
stoichiometry: 1.0
species: 440834
type: SpeciesReference

441234
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

466067
stoichiometry: 1.0
species: 439834
type: SpeciesReference

445233
kinetic law: 466768
product: 466756
reactant: 466744
reactant: 466732
notes: 10 X raise oct 22 12 X raise oct 24 + conversion to k2 =4 * k3
fast: false
reversible: true
type: Reaction

444553
kinetic law: 465150
product: 465138
reactant: 465126
reactant: 465114
notes: Hasler et al FASEB J 6:2734-2741 1992 say Kd =1e-7M for type II, 5.6e-8 M for type I. Take mean which comes to 2e-13 #/cell Smith et al PNAS USA 78:3 1591-1595 1981 have better data. First kf/kb=2.1e7/M = 3.5e-5 (#/cell). Ogreid and Doskeland Febs Lett 129:2 287-292 1981 have figs suggesting time course of complete assoc is < 1 min.
fast: false
reversible: true
type: Reaction

353011
units: 462115
value: 2.250045E-14
type: LocalParameter

441274
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

466612
stoichiometry: 1.0
species: 439974
type: SpeciesReference

469526
stoichiometry: 1.0
species: 441494
type: SpeciesReference

469865
stoichiometry: 1.0
species: 443314
type: SpeciesReference

352995
units: 462115
value: 9.000045E-16
type: LocalParameter

467482
local parameters: 353041
local parameters: 353040
notes: k1*MAPK_slash_MAPK*MAPK_slash_MAPKK_star_-k2*MAPK_slash_MAPKK_star__slash_MAPKKtyr_slash_MAPKKtyr_cplx
type: KineticLaw

353087
units: 462030
value: 9.0E-15
type: LocalParameter

446873
kinetic law: 470800
product: 470788
reactant: 470776
reactant: 470764
fast: false
reversible: true
type: Reaction

462713
local parameters: 352784
local parameters: 352781
notes: kf*temp_minus_PIP2*PLA2_slash_PLA2_minus_cytosolic-kb*PLA2_slash_PIP2_minus_PLA2_star_
type: KineticLaw

463472
local parameters: 352832
local parameters: 352831
notes: kf*Gq_slash_G_minus_GDP*Gq_slash_Rec_minus_Glu-kb*Gq_slash_Rec_minus_Glu_minus_Gq
type: KineticLaw

352843
units: 462115
value: 9.000045E-14
type: LocalParameter

353119
units: 462030
value: 1.2E-16
type: LocalParameter

463906
stoichiometry: 1.0
species: 441374
type: SpeciesReference

470655
local parameters: 353240
notes: k3*CaM_po_Ca_pc_n_minus_CaNAB_slash_dephosph_neurogranin_slash_dephosph_neurogranin_cplx
type: KineticLaw

439974
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

471300
stoichiometry: 1.0
species: 443274
type: SpeciesReference

468557
stoichiometry: 1.0
species: 441014
type: SpeciesReference

463158
stoichiometry: 1.0
species: 440254
type: SpeciesReference

353016
units: 462115
value: 4.499955E-14
type: LocalParameter

465283
stoichiometry: 1.0
species: 442614
type: SpeciesReference

465511
stoichiometry: 1.0
species: 442814
type: SpeciesReference

352994
units: 462030
value: 5.25E-16
type: LocalParameter

469148
stoichiometry: 1.0
species: 442274
type: SpeciesReference

352848
units: 462030
value: 7.5E-16
type: LocalParameter

470546
stoichiometry: 1.0
species: 441954
type: SpeciesReference

443734
kinetic law: 462929
product: 462917
reactant: 462905
fast: false
reversible: true
type: Reaction

467458
stoichiometry: 1.0
species: 440674
type: SpeciesReference

464123
stoichiometry: 1.0
species: 441394
type: SpeciesReference

446513
kinetic law: 469926
product: 469914
reactant: 469901
reactant: 469889
notes: See Hanson and Schulman again, for afterburst rates of phosph.
fast: false
reversible: true
type: Reaction

462797
stoichiometry: 1.0
species: 440054
type: SpeciesReference

447153
kinetic law: 471481
product: 471469
product: 471457
reactant: 471445
fast: false
reversible: false
type: Reaction

353057
units: 462030
value: 4.5E-16
type: LocalParameter

353017
units: 462030
value: 7.2E-13
type: LocalParameter

447193
kinetic law: 471577
product: 471565
product: 471553
reactant: 471541
fast: false
reversible: false
type: Reaction

463424
local parameters: 352830
local parameters: 352827
notes: kf*G_star_GTP-kb*G_star_GDP
type: KineticLaw

353300
units: 462030
value: 2.7E-14
type: LocalParameter

447073
kinetic law: 471288
modifier: 471276
product: 471264
reactant: 471252
fast: false
reversible: false
type: Reaction

352993
units: 462030
value: 2.1E-15
type: LocalParameter

352849
units: 462115
value: 9.000045E-15
type: LocalParameter

463785
stoichiometry: 1.0
species: 441094
type: SpeciesReference

465355
stoichiometry: 1.0
species: 442634
type: SpeciesReference

439618
constant: false
boundary condition: false
has only substance units: false
initial concentration: 9.43511111111111E-21
initial amount: NaN
in compartment: 439494
type: Species

465403
stoichiometry: 1.0
species: 441294
type: SpeciesReference

468956
stoichiometry: 1.0
species: 441134
type: SpeciesReference

353056
units: 462030
value: 1.8E-15
type: LocalParameter

352992
units: 462115
value: 9.18E-17
type: LocalParameter

464776
stoichiometry: 1.0
species: 442274
type: SpeciesReference

353014
units: 462030
value: 3.6E-13
type: LocalParameter

443254
constant: true
boundary condition: true
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

446553
kinetic law: 470022
product: 470010
reactant: 469998
reactant: 469986
fast: false
reversible: true
type: Reaction

353116
units: 462115
value: 2.97E-16
type: LocalParameter

441874
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

445973
kinetic law: 468593
product: 468581
product: 468569
reactant: 468557
fast: false
reversible: false
type: Reaction

353055
units: 462115
value: 1.41426E-14
type: LocalParameter

467748
stoichiometry: 1.0
species: 440754
type: SpeciesReference

353015
units: 462030
value: 9.0E-14
type: LocalParameter

462821
stoichiometry: 1.0
species: 439774
type: SpeciesReference

441834
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

352991
units: 462030
value: 8.7E-16
type: LocalParameter

465427
stoichiometry: 1.0
species: 442694
type: SpeciesReference

353054
units: 462030
value: 4.5E-16
type: LocalParameter

353115
units: 462030
value: 1.35E-14
type: LocalParameter

353125
units: 462115
value: 4.499955E-15
type: LocalParameter

468666
stoichiometry: 1.0
species: 441134
type: SpeciesReference

466392
stoichiometry: 1.0
species: 439894
type: SpeciesReference

352905
units: 462115
value: 5.4E-15
type: LocalParameter

441994
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

441614
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

353080
units: 462030
value: 3.6E-14
type: LocalParameter

353009
units: 462030
value: 5.4E-14
type: LocalParameter

352946
units: 462030
value: 4.875E-14
type: LocalParameter

352779
units: 462115
value: 1.499985E-15
type: LocalParameter

470885
stoichiometry: 1.0
species: 442354
type: SpeciesReference

446293
kinetic law: 469368
product: 469356
product: 469344
reactant: 469332
fast: false
reversible: false
type: Reaction

445793
kinetic law: 468160
product: 468148
reactant: 468135
reactant: 468123
notes: See MKP1-tyr-deph
fast: false
reversible: true
type: Reaction

442034
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

441954
constant: false
boundary condition: false
has only substance units: false
initial concentration: 1.8
initial amount: NaN
in compartment: 439494
type: Species

441014
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

445013
kinetic law: 466223
product: 466211
product: 466199
reactant: 466187
fast: false
reversible: false
type: Reaction

468521
stoichiometry: 1.0
species: 440934
type: SpeciesReference

352906
units: 462030
value: 1.5E-14
type: LocalParameter

464231
stoichiometry: 1.0
species: 441594
type: SpeciesReference

441094
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

353165
units: 462030
value: 3.0E-15
type: LocalParameter

446933
kinetic law: 470945
product: 470933
product: 470921
reactant: 470909
fast: false
reversible: false
type: Reaction

465307
stoichiometry: 1.0
species: 442614
type: SpeciesReference

471240
local parameters: 353297
local parameters: 353294
notes: kcat*AC_slash_AC2_star_*AC_slash_ATP/(Km+AC_slash_ATP)
type: KineticLaw

469743
stoichiometry: 1.0
species: 441874
type: SpeciesReference

353270
units: 462115
value: 5.94E-15
type: LocalParameter

463194
local parameters: 352816
local parameters: 352813
notes: kf*PLCbeta_slash_PLC*G_star_GTP-kb*PLCbeta_slash_PLC_minus_Gq
type: KineticLaw

468908
stoichiometry: 1.0
species: 441254
type: SpeciesReference

353008
units: 462030
value: 2.16E-13
type: LocalParameter

466404
stoichiometry: 1.0
species: 442774
type: SpeciesReference

462335
stoichiometry: 1.0
species: 439618
type: SpeciesReference

467344
stoichiometry: 1.0
species: 440314
type: SpeciesReference

463569
stoichiometry: 1.0
species: 440474
type: SpeciesReference

463254
stoichiometry: 1.0
species: 440454
type: SpeciesReference

352839
units: 462115
value: 9.000045E-16
type: LocalParameter

352903
units: 462067
value: 1.08000135E-13
type: LocalParameter

MODEL9089914876
species: 439794
species: 443314
reaction: 444893
reaction: 447073
compartment: 439494
reaction: 446813
reaction: 445034
species: 441214
area units: area
reaction: 446533
species: 442994
reaction: 447093
species: 443054
species: 443194
species: 442694
reaction: 447133
reaction: 444453
species: 440614
species: 442874
species: 441354
reaction: 446713
species: 442014
reaction: 445613
species: 441094
reaction: 445573
reaction: 445073
species: 442774
reaction: 445113
reaction: 446933
compartment: 439514
reaction: 445513
species: 441814
species: 442054
reaction: 444053
species: 440554
reaction: 445533
reaction: 445313
species: 441554
species: 440034
species: 441734
species: 439994
reaction: 444073
species: 440194
species: 440374
reaction: 443474
species: 442234
reaction: 445833
reaction: 447213
reaction: 445793
reaction: 445293
reaction: 445333
species: 442914
units def: 462030
species: 439594
species: 440854
reaction: 444173
species: 443114
reaction: 444273
species: 439634
reaction: 444193
species: 441774
species: 443034
reaction: 443594
reaction: 446913
reaction: 444293
reaction: 443694
species: 441014
reaction: 443813
species: 439694
species: 441674
units def: 462115
reaction: 443913
species: 443214
species: 441754
species: 442834
species: 441294
species: 440894
reaction: 444393
species: 442134
species: 442554

468329
stoichiometry: 1.0
species: 440934
type: SpeciesReference

469223
local parameters: 353113
local parameters: 353112
notes: k1*AC_slash_cAMP_minus_PDE*PKA_minus_active-k2*PKA_minus_active_slash_phosph_minus_PDE_slash_phosph_minus_PDE_cplx
type: KineticLaw

353007
units: 462115
value: 1.35E-14
type: LocalParameter

352777
units: 462115
value: 2.7E-17
type: LocalParameter

464620
stoichiometry: 1.0
species: 442154
type: SpeciesReference

446733
kinetic law: 470460
product: 470447
product: 470435
reactant: 470423
fast: false
reversible: false
type: Reaction

470996
local parameters: 353273
local parameters: 353270
notes: k1*PP1_slash_PP1_minus_I1_star_*PP2A-k2*PP2A_slash_PP2A_minus_dephosph_minus_PP1_minus_I_star__slash_PP2A_minus_dephosph_minus_PP1_minus_I_star__cplx
type: KineticLaw

352838
units: 462067
value: 0.0
type: LocalParameter

468365
stoichiometry: 1.0
species: 440974
type: SpeciesReference

471203
stoichiometry: 1.0
species: 443274
type: SpeciesReference

353162
units: 462115
value: 3.30102E-17
type: LocalParameter

467383
stoichiometry: 1.0
species: 440334
type: SpeciesReference

467279
stoichiometry: 1.0
species: 439754
type: SpeciesReference

465475
stoichiometry: 1.0
species: 442734
type: SpeciesReference

352904
units: 462030
value: 1.08E-13
type: LocalParameter

353006
units: 462030
value: 1.656E-14
type: LocalParameter

352943
units: 462115
value: 1.1249955E-13
type: LocalParameter

352778
units: 462030
value: 3.0E-15
type: LocalParameter

466551
stoichiometry: 1.0
species: 439974
type: SpeciesReference

440154
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

445813
kinetic law: 468208
product: 468196
product: 468184
reactant: 468172
fast: false
reversible: false
type: Reaction

440194
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

352942
units: 462030
value: 1.65E-13
type: LocalParameter

470203
stoichiometry: 1.0
species: 441994
type: SpeciesReference

352880
units: 462030
value: 2.52E-17
type: LocalParameter

445173
kinetic law: 466624
product: 466612
product: 466600
reactant: 466587
fast: false
reversible: false
type: Reaction

443454
kinetic law: 462224
product: 462212
reactant: 462200
reactant: 462188
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

470933
stoichiometry: 1.0
species: 442334
type: SpeciesReference

444773
kinetic law: 465669
product: 465657
reactant: 465645
reactant: 465633
notes: kb/kf = 1.2 nM so kf = kb/720 = 1.3888 * kb.
fast: false
reversible: true
type: Reaction

444373
kinetic law: 464728
product: 464716
reactant: 464704
reactant: 464692
notes: Surprisingly, no direct info on rates from neurogranin at this time. These rates are based on GAP-43 binding studies. As GAP-43 and neurogranin share near identity in the CaM/PKC binding regions, and also similarity in phosph and dephosph rates, I am borrowing GAP-43 kinetic info. See Alexander et al JBC 262:13 6108-6113 1987
fast: false
reversible: true
type: Reaction

467676
local parameters: 353050
local parameters: 353047
notes: k1*MAPK_slash_MAPKK*MAPK_slash_Raf_minus_GTP_minus_Ras-k2*MAPK_slash_Raf_minus_GTP_minus_Ras_slash_Raf_minus_GTP_minus_Ras_dot_1_slash_Raf_minus_GTP_minus_Ras_dot_1_cplx
type: KineticLaw

471068
stoichiometry: 1.0
species: 442394
type: SpeciesReference

352902
units: 462030
value: 0.0
type: LocalParameter

445613
kinetic law: 467724
product: 467712
product: 467700
reactant: 467688
fast: false
reversible: false
type: Reaction

463713
stoichiometry: 1.0
species: 440814
type: SpeciesReference

353122
units: 462030
value: 3.0E-17
type: LocalParameter

470191
stoichiometry: 1.0
species: 441954
type: SpeciesReference

352776
units: 462030
value: 1.5E-16
type: LocalParameter

466139
stoichiometry: 1.0
species: 442134
type: SpeciesReference

440474
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

352941
units: 462115
value: 1.1249955E-13
type: LocalParameter

353083
units: 462115
value: 2.87415E-15
type: LocalParameter

466259
stoichiometry: 1.0
species: 439874
type: SpeciesReference

443034
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

470472
stoichiometry: 1.0
species: 441834
type: SpeciesReference

467058
local parameters: 353026
local parameters: 353023
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

470142
stoichiometry: 1.0
species: 441774
type: SpeciesReference

471385
local parameters: 353315
local parameters: 353312
notes: kcat*AC_slash_AC2_star__minus_Gs*AC_slash_ATP/(Km+AC_slash_ATP)
type: KineticLaw

352881
units: 462030
value: 1.5E-18
type: LocalParameter

470313
local parameters: 353210
local parameters: 353207
notes: k1*CaMKII_slash_CaMK_minus_thr306*PP1_minus_active-k2*PP1_minus_active_slash_Deph_minus_thr306_slash_Deph_minus_thr306_cplx
type: KineticLaw

439834
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

466720
local parameters: 353009
notes: k3*PLA2_slash_PIP2_minus_Ca_minus_PLA2_star__slash_kenz_slash_kenz_cplx
type: KineticLaw

439874
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

465584
stoichiometry: 1.0
species: 443054
type: SpeciesReference

466515
stoichiometry: 1.0
species: 439934
type: SpeciesReference

352940
units: 462030
value: 4.95E-14
type: LocalParameter

352999
units: 462115
value: 2.025E-15
type: LocalParameter

352773
units: 462115
value: 9.000045E-19
type: LocalParameter

462603
stoichiometry: 1.0
species: 439714
type: SpeciesReference

465838
local parameters: 352976
local parameters: 352975
notes: kf*Ca_input-kb*Ca
type: KineticLaw

443514
kinetic law: 462347
product: 462335
reactant: 462322
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

465175
stoichiometry: 1.0
species: 442714
type: SpeciesReference

470607
local parameters: 353237
local parameters: 353234
notes: k1*CaM_slash_neurogranin_star_*CaM_po_Ca_pc_n_minus_CaNAB-k2*CaM_po_Ca_pc_n_minus_CaNAB_slash_dephosph_neurogranin_slash_dephosph_neurogranin_cplx
type: KineticLaw

353273
units: 462030
value: 3.75E-14
type: LocalParameter

464981
stoichiometry: 1.0
species: 442174
type: SpeciesReference

353081
units: 462030
value: 9.0E-15
type: LocalParameter

467931
stoichiometry: 1.0
species: 440734
type: SpeciesReference

442414
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

470582
stoichiometry: 1.0
species: 443354
type: SpeciesReference

352884
units: 462030
value: 2.52E-17
type: LocalParameter

352771
units: 462115
value: 1.799955E-19
type: LocalParameter

352833
units: 462115
value: 2.520045E-14
type: LocalParameter

463821
stoichiometry: 1.0
species: 441134
type: SpeciesReference

446073
kinetic law: 468834
product: 468822
reactant: 468810
reactant: 468798
notes: From Eccleston et al JBC 268(36)pp27012-19 get Kd < 2uM, kcat - 10/sec From Martin et al Cell 63 843-849 1990 get Kd ~ 250 nM, kcat = 20/min I will go with the Eccleston figures as there are good error bars (10%). In general the values are reasonably close. k1 = 1.666e-3/sec, k2 = 1000/sec, k3 = 10/sec (note k3 is rate-limiting) 5 Nov 2002: Changed ratio term to 4 from 100. Now we have k1=8.25e-5; k2=40, k3=10. k3 is still rate-limiting.
fast: false
reversible: true
type: Reaction

464279
stoichiometry: 1.0
species: 441674
type: SpeciesReference

470824
stoichiometry: 1.0
species: 442314
type: SpeciesReference

467784
stoichiometry: 1.0
species: 440794
type: SpeciesReference

467167
stoichiometry: 1.0
species: 440214
type: SpeciesReference

465886
local parameters: 352978
local parameters: 352977
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

353225
units: 462115
value: 5.147955E-16
type: LocalParameter

442214
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

352772
units: 462030
value: 1.5E-16
type: LocalParameter

465247
local parameters: 352942
local parameters: 352941
notes: kf*PKA_slash_R2C2_minus_cAMP2*cAMP-kb*PKA_slash_R2C2_minus_cAMP3
type: KineticLaw

352832
units: 462030
value: 1.5E-19
type: LocalParameter

352885
units: 462115
value: 2.7E-13
type: LocalParameter

466368
stoichiometry: 1.0
species: 439894
type: SpeciesReference

444453
kinetic law: 464909
product: 464897
reactant: 464885
reactant: 464873
notes: This process is probably much more complicated and involves CaM. However, as I can\'t find detailed info I am bundling this into a single step. Based on Steemer and Klee pg 6863, the Kact is 0.5 uM. kf/kb = 1/(0.5 * 6e5)^2 = 1.11e-11
fast: false
reversible: true
type: Reaction

353279
units: 462115
value: 5.13E-17
type: LocalParameter

462640
stoichiometry: 1.0
species: 443074
type: SpeciesReference

466876
stoichiometry: 1.0
species: 440114
type: SpeciesReference

352882
units: 462030
value: 0.0
type: LocalParameter

462043
exponent: 1.0
scale: 0
multipler: 1.0
kind: LITRE
type: SBMLUnit

352831
units: 462115
value: 9.000045E-18
type: LocalParameter

443814
kinetic law: 463290
product: 463278
reactant: 463266
reactant: 463254
notes: kf = kf from text = 1e7 / M / sec = 10 /uM/sec = 10 / 6e5 / # / sec = 1.67e-5 kb = kr from text = 60 / sec Note that we continue to use uM here since [phenylephrine] is also in uM. From Martin et al FEBS Lett 316:2 191-196 1993 we have Kd = 600 nM Assuming kb = 10/sec, we get kf = 10/(0.6 uM * 6e5) = 2.8e-5 1/sec/#
fast: false
reversible: true
type: Reaction

463520
local parameters: 352836
local parameters: 352833
notes: kf*Glu*Gq_slash_Rec_minus_Gq-kb*Gq_slash_Rec_minus_Glu_minus_Gq
type: KineticLaw

462965
stoichiometry: 1.0
species: 440274
type: SpeciesReference

464303
stoichiometry: 1.0
species: 441714
type: SpeciesReference

353276
units: 462030
value: 9.0E-15
type: LocalParameter

440714
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

469986
stoichiometry: 1.0
species: 441774
type: SpeciesReference

352883
units: 462115
value: 3.75003E-17
type: LocalParameter

352770
units: 462030
value: 7.5E-14
type: LocalParameter

469198
stoichiometry: 1.0
species: 441294
type: SpeciesReference

443813
kinetic law: 463242
product: 463230
reactant: 463218
reactant: 463206
notes: this step has a high affinity for Ca, from Smrcka et al. 0.1uM so kf /kb = 1/6e4 = 1.666e-5:1. See the Act-PLC-by-Gq reac. 11 Jun 1996: Raised kf to 5e-5 based on match to conc-eff curves from Smrcka et al.
fast: false
reversible: true
type: Reaction

352830
units: 462030
value: 0.0
type: LocalParameter

442734
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

444873
kinetic law: 465886
product: 465874
reactant: 465862
reactant: 465850
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

465983
local parameters: 352981
local parameters: 352980
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

470716
stoichiometry: 1.0
species: 442214
type: SpeciesReference

466924
stoichiometry: 1.0
species: 439914
type: SpeciesReference

468992
stoichiometry: 1.0
species: 441074
type: SpeciesReference

471349
stoichiometry: 1.0
species: 443274
type: SpeciesReference

353228
units: 462030
value: 2.1E-15
type: LocalParameter

352888
units: 462030
value: 1.5E-14
type: LocalParameter

471020
stoichiometry: 1.0
species: 442314
type: SpeciesReference

352837
units: 462030
value: 1.5E-17
type: LocalParameter

466283
stoichiometry: 1.0
species: 439874
type: SpeciesReference

466211
stoichiometry: 1.0
species: 443294
type: SpeciesReference

471553
stoichiometry: 1.0
species: 442854
type: SpeciesReference

353351
units: 462030
value: 1.5E-14
type: LocalParameter

443634
kinetic law: 462615
product: 462603
reactant: 462591
reactant: 462579
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

444193
kinetic law: 464315
product: 464303
reactant: 464291
reactant: 464279
notes: Nice curves from Homma et al JBC 263:14 6592-6598 1988 Fig 5c. The activity falls above 10 uM, but that is too high to reach physiologically anyway, so we\'ll ignore the higher pts and match the lower ones only. Half-max at 1 uM. But Wahl et al JBC 267:15 10447-10456 1992 have half-max at 56 nM which is what I\'ll use.
fast: false
reversible: true
type: Reaction

462905
stoichiometry: 1.0
species: 440134
type: SpeciesReference

462530
stoichiometry: 1.0
species: 439734
type: SpeciesReference

469088
stoichiometry: 1.0
species: 442254
type: SpeciesReference

352889
units: 462115
value: 1.799955E-14
type: LocalParameter

352836
units: 462030
value: 1.5E-16
type: LocalParameter

444153
kinetic law: 464219
product: 464207
reactant: 464195
notes: The only clue I have to these rates is from the time courses of the EGF activation, which is around 1 to 5 min. The dephosph would be expected to be of the same order, perhaps a bit longer. Lets use 0.002 which is about 8 min. Sep 17: The transient activation curve matches better with kf = 0.001
fast: false
reversible: true
type: Reaction

445073
kinetic law: 466380
product: 466368
reactant: 466356
reactant: 466343
notes: Phorbol esters have little effect on AC1 or on the Gs-stimulation of AC2. So in this model we are only dealing with the increase in basal activation of AC2 induced by PKC k1 = 1.66e-6 k2 = 16 k3 =4
fast: false
reversible: true
type: Reaction

443674
kinetic law: 462713
product: 462701
reactant: 462689
reactant: 462677
fast: false
reversible: true
type: Reaction

445933
kinetic law: 468497
product: 468485
product: 468473
reactant: 468461
fast: false
reversible: false
type: Reaction

464388
stoichiometry: 1.0
species: 441714
type: SpeciesReference

440894
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

468846
stoichiometry: 1.0
species: 441214
type: SpeciesReference

442174
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

471565
stoichiometry: 1.0
species: 442934
type: SpeciesReference

445533
kinetic law: 467530
product: 467518
product: 467506
reactant: 467494
fast: false
reversible: false
type: Reaction

442294
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

463086
stoichiometry: 1.0
species: 440314
type: SpeciesReference

352949
units: 462030
value: 9.0E-14
type: LocalParameter

463146
local parameters: 352812
local parameters: 352811
notes: kf*PLCbeta_slash_PLC_minus_Ca_minus_Gq-kb*G_star_GDP*PLCbeta_slash_PLC_minus_Ca
type: KineticLaw

462445
stoichiometry: 1.0
species: 439734
type: SpeciesReference

469332
stoichiometry: 1.0
species: 441414
type: SpeciesReference

468702
stoichiometry: 1.0
species: 441154
type: SpeciesReference

465657
stoichiometry: 1.0
species: 442874
type: SpeciesReference

469635
stoichiometry: 1.0
species: 443214
type: SpeciesReference

353168
units: 462030
value: 7.5E-16
type: LocalParameter

442794
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 439494
type: Species

464510
stoichiometry: 1.0
species: 441754
type: SpeciesReference

463605
stoichiometry: 1.0
species: 440454
type: SpeciesReference

352948
units: 462115
value: 2.7E-14
type: LocalParameter

468884
local parameters: 353099
notes: k3*Ras_slash_GAP_slash_GAP_minus_inact_minus_ras_slash_GAP_minus_inact_minus_ras_cplx
type: KineticLaw

352947
units: 462030
value: 9.0E-14
type: LocalParameter

462689
stoichiometry: 1.0
species: 439914
type: SpeciesReference

464412
stoichiometry: 1.0
species: 441374
type: SpeciesReference

439534
constant: false
boundary condition: false
has only substance units: false
initial concentration: 3.72077777777778E-17
initial amount: NaN
in compartment: 439494
type: Species

462929
local parameters: 352798
local parameters: 352797
notes: kf*PLA2_slash_PLA2_star_-kb*PLA2_slash_PLA2_minus_cytosolic
type: KineticLaw

471625
local parameters: 353339
local parameters: 353336
notes: k1*cAMP*AC_slash_PDE1-k2*AC_slash_PDE1_slash_PDE1_slash_PDE1_cplx
type: KineticLaw

463677
local parameters: 352844
local parameters: 352843
notes: kf*Gq_slash_Rec_minus_Gq*Gq_slash_mGluRAntag-kb*Gq_slash_Blocked_minus_rec_minus_Gq
type: KineticLaw

470252
stoichiometry: 1.0
species: 441954
type: SpeciesReference