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BIOMD0000000049 - Sasagawa2005_MAPK

 

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Reference Publication
Publication ID: 15793571
Sasagawa S, Ozaki Y, Fujita K, Kuroda S.
Prediction and validation of the distinct dynamics of transient and sustained ERK activation.
Nat. Cell Biol. 2005 Apr; 7(4): 365-373
Undergraduate Program for Bioinformatics and Systems Biology, Graduate School of Information Science and Technology, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.  [more]
Model
Original Model: BIOMD0000000049.origin
Submitter: Shinya Kuroda
Submission ID: MODEL6624243033
Submission Date: 12 Jan 2006 13:42:52 UTC
Last Modification Date: 04 Apr 2014 13:27:04 UTC
Creation Date: 21 Dec 2005 10:59:39 UTC
Encoders:  Lu Li
   Shinya Kuroda
set #1
bqmodel:isDerivedFrom BioModels Database Bhalla2002_MAPK-bistability-fig1c
BioModels Database Bhalla2002_mkp1_feedback_effects
BioModels Database Schoeberl2002_EGF_MAPK
BioModels Database Bhalla1999_3d_fold_model
BioModels Database Hatakeyama2003_MAPK
PubMed 14751248
PubMed 11832340
PubMed 11024454
set #2
bqbiol:isVersionOf Gene Ontology ERK1 and ERK2 cascade
set #3
bqbiol:hasProperty Mathematical Modelling Ontology MAMO_0000046
set #4
bqbiol:hasPart Gene Ontology MAPK cascade
Gene Ontology neurotrophin TRK receptor signaling pathway
Gene Ontology Ras protein signal transduction
Gene Ontology epidermal growth factor receptor signaling pathway
bqbiol:hasTaxon Taxonomy Rattus
Notes

This a model from the article:
Prediction and validation of the distinct dynamics of transient and sustained ERK activation.
Sasagawa S, Ozaki Y, Fujita K, Kuroda S Nat. Cell Biol.[2005 Apr; Volume: 7 (Issue: 4 )]: 365-73 15793571,
Abstract:
To elucidate the hidden dynamics of extracellular-signal-regulated kinase (ERK) signalling networks, we developed a simulation model of ERK signalling networks by constraining in silico dynamics based on in vivo dynamics in PC12 cells. We predicted and validated that transient ERK activation depends on rapid increases of epidermal growth factor and nerve growth factor (NGF) but not on their final concentrations, whereas sustained ERK activation depends on the final concentration of NGF but not on the temporal rate of increase. These ERK dynamics depend on Ras and Rap1 dynamics, the inactivation processes of which are growth-factor-dependent and -independent, respectively. Therefore, the Ras and Rap1 systems capture the temporal rate and concentration of growth factors, and encode these distinct physical properties into transient and sustained ERK activation, respectively.

Dynamics of active Ras, active Rap1 and phosphorylated ERK were correctly reproduced with CellDesigner 3.0

This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2012 The BioModels.net Team.
For more information see the terms of use.
To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.

Model
Publication ID: 15793571 Submission Date: 12 Jan 2006 13:42:52 UTC Last Modification Date: 04 Apr 2014 13:27:04 UTC Creation Date: 21 Dec 2005 10:59:39 UTC
Mathematical expressions
Reactions
form_EGFreceptor EGFbinding dimerization binding_SOS_Grb2
binding_pSOS_Grb2 EGFRphosphorylation binding_cCbI_dpEGFR binding_pShc_LdpEGFR
pDOKdephosphorylation binding_cCbl_pShc_dpEGFR SOSdephosphorylation pSOS_Grb2_dephosphorylation
binding_Shc_LdpEGFR Shc_dpEGFR_phosphorylation dpEGFR_c_Cbl_ubiquitination dpEGFR_cCbl_degrad
binding_cCbl_Shc_dpEGFR Shc_dpEGFR_c_CBl_Ubiquitination Shc_dpEGFR_c_Cbl_ubiq_Degradation pShc_dpEGFR_c_Cbl_ubiquitination
pShc_dpEGFR_c_Cbl_ubiq_degradation Shc_dpEGFR_c_Cblphosphorylation binding_Grb2_SOS_pShc binding_Grb2_SOS_pShc_dpEGFR
binding_Grb2_SOS_pShc_dpEGFR binding_c_Cbl_Grb2_SOS_pShc_dpEGFR binding_Grb2_SOS_pShc_to_dpEGFR_c_Cbl Grb2_SOS_pShc_dpEGFR_c_Cbl_ubiquitination
Grb2_SOS_pShc_dpEGFR_c_Cbl_ubiq_degradation Grb2_SOS_pShc_Dissociation J31 pShc_dephosphorylation
pFRS2_dephosphorylation binding_Crk_to_C3G binding_L_dpEGFR_to_FRS2 binding_pFRS2_to_L_dpEGFR
FRS2_dpEGFRphsphorylation binding_Crk_C3G_to_pFRS2_pRTK binding_c_Cbl_to_FRS2_dpEGFR binding_c_Cbl_to_pFRS2_dpEGFR
pFRS2_dpEGFR_c_Cbl_ubiquitiation FRS2_dpEGFR_c_Cbl_ubiquitination FRS2_dpEGFR_c_Cbl_phosphorylation binding_Crk_C3G_to_pFRS2_pFRS2_dpEGFR_c_Cbl
Crk_C3G_pFRS2_dpEGFR_c_Cbl_ubiquitination FRS2_dpEGFR_c_Cbl_ubiq_dissociation pFRS2_dpEGFR_c_Cbl_ubiq_dissociation binding_RasGAP_to_pDOK
SOS_Grb2_phosphorylation SOS_phosphorylation binding_c_Raf_to_Ras_GTP binding_B_Raf_to_Rap1_GTP
binding_B_Raf_to_Ras_GTP ppMEK_dephosphorylation pMEK_dephosphorylation ppMEK_ERK
pMEK_ERK_dephosphorylation ppERK_dimerization Ras_GTP_dephosphorylation Rap1_GTP_dephosphorylation
Rap1_GTP_phosphorylation Ras_GDP_phosphorylation binding_NGF_to_NGFR TrkA_phosphorylation
pTrkA_intermalization pTrkA_endo_degradation pTrkA_degradation binding_Shc_to_pTrkA
binding_pShc_to_pTrkA binding_FRS2_to_pTrkA binding_pFRS2_to_pTrkA binding_Shc_to_pTrkA_endo
binding_pShc_to_pTrkA_endo Shc_pTrkA_endo_phosphorylation Shc_pTrkA_phosphorylation pFRS2_pTrkA_phosphorylation
binding_FRS2_to_pTrkA_endo binding_pFRS2_to_pTrkA_endo FRS2_pTrkA_endo_phosphorylation FRS2_pTrkA_degradation
pFRS2_pTrkA_degradation Shc_pTrkA_degradation pShc_pTrkA_degradation FRS2_pTrkA_endo_degradation
Shc_pTrkA_endo_degradation pShc_pTrkA_endo_degradation binding_Grb2_SOS_to_pShc_pTrkA_endo binding_Grb2_SOS_to_pShc_pTrkA
Grb2_SOS_pShc_pTrkA_ubiquitination Crk_C3G_pFRS2_pTrkA_ubiquitination pFRS2_pTrkA_ubiquitination FRS2_pTrkA_ubiquitination
pShc_pTrkA_ubiquitination Shc_pTrkA_ubiquitination binding_Crk_C3G_to_pFRS2_pTrkA binding_Crk_C3G_to_pFRS2_pTrkA_endo
binding_Grb2_SOS_pShc_to_pTrkA binding_Grb2_SOS_pShc_to_pTrkA_endo Crk_C3G_pFRS2_pTrkA_degradation Crk_C3G_pFRS2_pTrkA_endo_degradation
Grb2_SOS_pShc_pTrkA_degradation Grb2_SOS_pShc_pTrkA_endo_degradation pFRS2_pTrkA_endo_degradation form_NGFreceptor
binding_Shc_to_dpEGFR_c_Cbl binding_pShc_to_dpEGFR_c_Cbl binding_SOS_Grb2_to_pShc_dpEGFR_c_Cbl binding_c_Cbl_to_Crk_C3G_pFRS2_dpEGFR
binding_FRS2_to_dpEGFR_c_Cbl binding_pFRS2_to_dpEGFR_c_Cbl Ras_GTP_dephosphorylation RAP1_GTP_dephosphorylation
Dok_phosphorylation Grb1_SOS_pShc_dissociation binding_MEK_to_ERK binding_ERK_to_pMEK
binding_ERK_to_ppMEK ppMEK_ERK_dissociation c_Raf_Ras_GTP_dissociation B_Raf_Ras_GTP_dissociation
B_Raf_Rap1_GTP_dissociation J140 J141 J142
J143 J144 J145 J146
J147 J148 J149 J150
J151 J152 J153 J154
J155 J156 J157 J158
J159 J160 J161 J162
J163 J164 J165 J166
J167 J168    
Physical entities
Compartments Species
compartment EGFR L_EGFR L_EGFR_dimer
L_dpEGFR NGFR pTrkA
L_NGFR NGF EGF
     
c1 SOS pSOS SOS_Grb2
Grb2 Dok pDok
Crk FRS2 Shc
pSOS_Grb2 Rap1_GDP MEK
MKP3 pShc_dpEGFR dpEGFR_c_Cbl
B_Raf_Rap1_GTP pShc_dpEGFR_c_Cbl pFRS2_dpEGFR_c_Cbl
Shc_dpEGFR c_Cbl RasGAP
c_Raf B_Raf ERK
PP2A Ras_GDP Rap1GAP
C3G pShc pFRS2_dpEGFR
pTrkA_endo MEK_ERK pMEK_ERK
FRS2_dpEGFR_c_Cbl_ubiq Crk_C3G_pFRS2_dpEGFR_c_Cbl pShc_dpEGFR_c_Cbl_ubiq
Crk_C3G_pFRS2_dpEGFR Grb2_SOS_pShc_dpEGFR_c_Cbl_ubiq Grb2_SOS_pShc_dpEGFR_c_Cbl
Shc_dpEGFR_c_Cbl_ubiq dpEGFR_c_Cbl_ubiq proteasome
Grb2_SOS_pShc Shc_dpEGFR_c_Cbl Grb2_SOS_pShc_dpEGFR
pFRS2 FRS2_dpEGFR pDok_RasGAP
pMEK FRS2_dpEGFR_c_Cbl pFRS2_dpEGFR_c_Cbl_ubiq
Ras_GTP Crk_C3G_pFRS2_dpEGFR_c_Cbl_ubiq c_Raf_Ras_GTP
B_Raf_Ras_GTP ppMEK ppERK
Crk_C3G Rap1_GTP ppMEK_ERK
dppERK Shc_pTrkA Shc_pTrkA_endo
pShc_pTrkA pFRS2_pTrkA FRS2_pTrkA
pShc_pTrkA_endo FRS2_pTrkA_endo pFRS2_pTrkA_endo
Crk_C3G_pFRS2_pTrkA_endo Grb2_SOS_pShc_pTrkA Crk_C3G_pFRS2_pTrkA
Grb2_SOS_pShc_pTrkA_endo c_Raf_Ras_GTP_MEK c_Raf_Ras_GTP_pMEK
c_Raf_Ras_GTP_MEK_ERK c_Raf_Ras_GTP_pMEK_ERK B_Raf_Ras_GTP_MEK
B_Raf_Ras_GTP_pMEK B_Raf_Ras_GTP_MEK_ERK B_Raf_Ras_GTP_pMEK_ERK
B_Raf_Rap1_GTP_MEK B_Raf_Rap1_GTP_pMEK B_Raf_Rap1_GTP_MEK_ERK
B_Raf_Rap1_GTP_pMEK_ERK ppERK_MKP3 dppERK_MKP3
pro_TrkA pro_EGFR degradation
Reactions (150)
 
 form_EGFreceptor [pro_EGFR] ↔ [EGFR];  
 
 EGFbinding [EGF] + [EGFR] ↔ [L_EGFR];  
 
 dimerization 2.0 × [L_EGFR] ↔ [L_EGFR_dimer];  
 
 binding_SOS_Grb2 [SOS] + [Grb2] ↔ [SOS_Grb2];  
 
 binding_pSOS_Grb2 [Grb2] + [pSOS] ↔ [pSOS_Grb2];  
 
 EGFRphosphorylation [L_EGFR_dimer] ↔ [L_dpEGFR];  
 
 binding_cCbI_dpEGFR [L_dpEGFR] + [c_Cbl] ↔ [dpEGFR_c_Cbl];  
 
 binding_pShc_LdpEGFR [L_dpEGFR] + [pShc] ↔ [pShc_dpEGFR];  
 
 pDOKdephosphorylation [pDok] ↔ [Dok];  
 
 binding_cCbl_pShc_dpEGFR [c_Cbl] + [pShc_dpEGFR] ↔ [pShc_dpEGFR_c_Cbl];  
 
 SOSdephosphorylation [pSOS] → [SOS];  
 
 pSOS_Grb2_dephosphorylation [pSOS_Grb2] → [SOS_Grb2];  
 
 binding_Shc_LdpEGFR [L_dpEGFR] + [Shc] ↔ [Shc_dpEGFR];  
 
 Shc_dpEGFR_phosphorylation [Shc_dpEGFR] → [pShc_dpEGFR];  
 
 dpEGFR_c_Cbl_ubiquitination [dpEGFR_c_Cbl] → [dpEGFR_c_Cbl_ubiq];  
 
 dpEGFR_cCbl_degrad [dpEGFR_c_Cbl_ubiq] → [proteasome] + [c_Cbl];  
 
 binding_cCbl_Shc_dpEGFR [c_Cbl] + [Shc_dpEGFR] ↔ [Shc_dpEGFR_c_Cbl];  
 
 Shc_dpEGFR_c_CBl_Ubiquitination [Shc_dpEGFR_c_Cbl] → [Shc_dpEGFR_c_Cbl_ubiq];  
 
 Shc_dpEGFR_c_Cbl_ubiq_Degradation [Shc_dpEGFR_c_Cbl_ubiq] → [proteasome] + [c_Cbl] + [Shc];  
 
 pShc_dpEGFR_c_Cbl_ubiquitination [pShc_dpEGFR_c_Cbl] → [pShc_dpEGFR_c_Cbl_ubiq];  
 
 pShc_dpEGFR_c_Cbl_ubiq_degradation [pShc_dpEGFR_c_Cbl_ubiq] → [proteasome] + [c_Cbl] + [pShc];  
 
 Shc_dpEGFR_c_Cblphosphorylation [Shc_dpEGFR_c_Cbl] → [pShc_dpEGFR_c_Cbl];  
 
 binding_Grb2_SOS_pShc [pShc] + [SOS_Grb2] ↔ [Grb2_SOS_pShc];  
 
 binding_Grb2_SOS_pShc_dpEGFR [L_dpEGFR] + [Grb2_SOS_pShc] ↔ [Grb2_SOS_pShc_dpEGFR];  
 
 binding_Grb2_SOS_pShc_dpEGFR [pShc_dpEGFR] + [SOS_Grb2] ↔ [Grb2_SOS_pShc_dpEGFR];  
 
 binding_c_Cbl_Grb2_SOS_pShc_dpEGFR [c_Cbl] + [Grb2_SOS_pShc_dpEGFR] ↔ [Grb2_SOS_pShc_dpEGFR_c_Cbl];  
 
 binding_Grb2_SOS_pShc_to_dpEGFR_c_Cbl [dpEGFR_c_Cbl] + [Grb2_SOS_pShc] ↔ [Grb2_SOS_pShc_dpEGFR_c_Cbl];  
 
 Grb2_SOS_pShc_dpEGFR_c_Cbl_ubiquitination [Grb2_SOS_pShc_dpEGFR_c_Cbl] → [Grb2_SOS_pShc_dpEGFR_c_Cbl_ubiq];  
 
 Grb2_SOS_pShc_dpEGFR_c_Cbl_ubiq_degradation [Grb2_SOS_pShc_dpEGFR_c_Cbl_ubiq] → [proteasome] + [c_Cbl] + [Grb2_SOS_pShc];  
 
 Grb2_SOS_pShc_Dissociation [Grb2_SOS_pShc] → [Shc] + [SOS_Grb2];  
 
 J31 [Dok] → [pDok];   {L_dpEGFR} , {Shc_dpEGFR} , {pShc_dpEGFR} , {Grb2_SOS_pShc_dpEGFR_c_Cbl} , {Grb2_SOS_pShc_dpEGFR} , {dpEGFR_c_Cbl} , {Shc_dpEGFR_c_Cbl} , {pShc_dpEGFR_c_Cbl} , {FRS2_dpEGFR} , {pFRS2_dpEGFR} , {Crk_C3G_pFRS2_dpEGFR} , {FRS2_dpEGFR_c_Cbl} , {Crk_C3G_pFRS2_dpEGFR_c_Cbl}
 
 pShc_dephosphorylation [pShc] → [Shc];  
 
 pFRS2_dephosphorylation [pFRS2] → [FRS2];  
 
 binding_Crk_to_C3G [Crk] + [C3G] ↔ [Crk_C3G];  
 
 binding_L_dpEGFR_to_FRS2 [L_dpEGFR] + [FRS2] ↔ [FRS2_dpEGFR];  
 
 binding_pFRS2_to_L_dpEGFR [L_dpEGFR] + [pFRS2] ↔ [pFRS2_dpEGFR];  
 
 FRS2_dpEGFRphsphorylation [FRS2_dpEGFR] → [pFRS2_dpEGFR];  
 
 binding_Crk_C3G_to_pFRS2_pRTK [pFRS2_dpEGFR] + [Crk_C3G] ↔ [Crk_C3G_pFRS2_dpEGFR];  
 
 binding_c_Cbl_to_FRS2_dpEGFR [FRS2_dpEGFR] + [c_Cbl] ↔ [FRS2_dpEGFR_c_Cbl];  
 
 binding_c_Cbl_to_pFRS2_dpEGFR [c_Cbl] + [pFRS2_dpEGFR] ↔ [pFRS2_dpEGFR_c_Cbl];  
 
 pFRS2_dpEGFR_c_Cbl_ubiquitiation [pFRS2_dpEGFR_c_Cbl] → [pFRS2_dpEGFR_c_Cbl_ubiq];  
 
 FRS2_dpEGFR_c_Cbl_ubiquitination [FRS2_dpEGFR_c_Cbl] → [FRS2_dpEGFR_c_Cbl_ubiq];  
 
 FRS2_dpEGFR_c_Cbl_phosphorylation [FRS2_dpEGFR_c_Cbl] → [pFRS2_dpEGFR_c_Cbl];  
 
 binding_Crk_C3G_to_pFRS2_pFRS2_dpEGFR_c_Cbl [pFRS2_dpEGFR_c_Cbl] + [Crk_C3G] ↔ [Crk_C3G_pFRS2_dpEGFR_c_Cbl];  
 
 Crk_C3G_pFRS2_dpEGFR_c_Cbl_ubiquitination [Crk_C3G_pFRS2_dpEGFR_c_Cbl] → [Crk_C3G_pFRS2_dpEGFR_c_Cbl_ubiq];  
 
 FRS2_dpEGFR_c_Cbl_ubiq_dissociation [FRS2_dpEGFR_c_Cbl_ubiq] → [proteasome] + [c_Cbl] + [FRS2];  
 
 pFRS2_dpEGFR_c_Cbl_ubiq_dissociation [pFRS2_dpEGFR_c_Cbl_ubiq] → [proteasome] + [c_Cbl] + [pFRS2];  
 
 binding_RasGAP_to_pDOK [pDok] + [RasGAP] ↔ [pDok_RasGAP];  
 
 SOS_Grb2_phosphorylation [SOS_Grb2] → [pSOS_Grb2];   {dppERK}
 
 SOS_phosphorylation [SOS] → [pSOS];   {dppERK}
 
 binding_c_Raf_to_Ras_GTP [c_Raf] + [Ras_GTP] ↔ [c_Raf_Ras_GTP];  
 
 binding_B_Raf_to_Rap1_GTP [Rap1_GTP] + [B_Raf] ↔ [B_Raf_Rap1_GTP];  
 
 binding_B_Raf_to_Ras_GTP [Ras_GTP] + [B_Raf] ↔ [B_Raf_Ras_GTP];  
 
 ppMEK_dephosphorylation [ppMEK] → [pMEK];   {PP2A}
 
 pMEK_dephosphorylation [pMEK] → [MEK];   {PP2A}
 
 ppMEK_ERK [ppMEK_ERK] → [pMEK_ERK];   {PP2A}
 
 pMEK_ERK_dephosphorylation [pMEK_ERK] → [MEK_ERK];   {PP2A}
 
 ppERK_dimerization 2.0 × [ppERK] ↔ [dppERK];  
 
 Ras_GTP_dephosphorylation [Ras_GTP] → [Ras_GDP];  
 
 Rap1_GTP_dephosphorylation [Rap1_GTP] → [Rap1_GDP];  
 
 Rap1_GTP_phosphorylation [Rap1_GDP] → [Rap1_GTP];   {Crk_C3G_pFRS2_dpEGFR_c_Cbl} , {Crk_C3G_pFRS2_dpEGFR} , {Crk_C3G_pFRS2_pTrkA_endo}
 
 Ras_GDP_phosphorylation [Ras_GDP] → [Ras_GTP];   {Grb2_SOS_pShc_dpEGFR_c_Cbl} , {Grb2_SOS_pShc_dpEGFR} , {Grb2_SOS_pShc_pTrkA}
 
 binding_NGF_to_NGFR [NGF] + [NGFR] ↔ [L_NGFR];  
 
 TrkA_phosphorylation [L_NGFR] → [pTrkA];  
 
 pTrkA_intermalization [pTrkA] → [pTrkA_endo];  
 
 pTrkA_endo_degradation [pTrkA_endo] → [degradation];  
 
 pTrkA_degradation [pTrkA] → [degradation];  
 
 binding_Shc_to_pTrkA [Shc] + [pTrkA] ↔ [Shc_pTrkA];  
 
 binding_pShc_to_pTrkA [pShc] + [pTrkA] ↔ [pShc_pTrkA];  
 
 binding_FRS2_to_pTrkA [FRS2] + [pTrkA] ↔ [FRS2_pTrkA];  
 
 binding_pFRS2_to_pTrkA [pFRS2] + [pTrkA] ↔ [pFRS2_pTrkA];  
 
 binding_Shc_to_pTrkA_endo [pTrkA_endo] + [Shc] ↔ [Shc_pTrkA_endo];  
 
 binding_pShc_to_pTrkA_endo [pTrkA_endo] + [pShc] ↔ [pShc_pTrkA_endo];  
 
 Shc_pTrkA_endo_phosphorylation [Shc_pTrkA_endo] → [pShc_pTrkA_endo];  
 
 Shc_pTrkA_phosphorylation [Shc_pTrkA] → [pShc_pTrkA];  
 
 pFRS2_pTrkA_phosphorylation [FRS2_pTrkA] → [pFRS2_pTrkA];  
 
 binding_FRS2_to_pTrkA_endo [pTrkA_endo] + [FRS2] ↔ [FRS2_pTrkA_endo];  
 
 binding_pFRS2_to_pTrkA_endo [pTrkA_endo] + [pFRS2] ↔ [pFRS2_pTrkA_endo];  
 
 FRS2_pTrkA_endo_phosphorylation [FRS2_pTrkA_endo] → [pFRS2_pTrkA_endo];  
 
 FRS2_pTrkA_degradation [FRS2_pTrkA] → [degradation] + [FRS2];  
 
 pFRS2_pTrkA_degradation [pFRS2_pTrkA] → [degradation] + [pFRS2];  
 
 Shc_pTrkA_degradation [Shc_pTrkA] → [degradation] + [Shc];  
 
 pShc_pTrkA_degradation [pShc_pTrkA] → [degradation] + [pShc];  
 
 FRS2_pTrkA_endo_degradation [FRS2_pTrkA_endo] → [degradation] + [FRS2];  
 
 Shc_pTrkA_endo_degradation [Shc_pTrkA_endo] → [degradation] + [Shc];  
 
 pShc_pTrkA_endo_degradation [pShc_pTrkA_endo] → [degradation] + [pShc];  
 
 binding_Grb2_SOS_to_pShc_pTrkA_endo [SOS_Grb2] + [pShc_pTrkA_endo] ↔ [Grb2_SOS_pShc_pTrkA_endo];  
 
 binding_Grb2_SOS_to_pShc_pTrkA [SOS_Grb2] + [pShc_pTrkA] ↔ [Grb2_SOS_pShc_pTrkA];  
 
 Grb2_SOS_pShc_pTrkA_ubiquitination [Grb2_SOS_pShc_pTrkA] → [Grb2_SOS_pShc_pTrkA_endo];  
 
 Crk_C3G_pFRS2_pTrkA_ubiquitination [Crk_C3G_pFRS2_pTrkA] → [Crk_C3G_pFRS2_pTrkA_endo];  
 
 pFRS2_pTrkA_ubiquitination [pFRS2_pTrkA] → [pFRS2_pTrkA_endo];  
 
 FRS2_pTrkA_ubiquitination [FRS2_pTrkA] → [FRS2_pTrkA_endo];  
 
 pShc_pTrkA_ubiquitination [pShc_pTrkA] → [pShc_pTrkA_endo];  
 
 Shc_pTrkA_ubiquitination [Shc_pTrkA] → [Shc_pTrkA_endo];  
 
 binding_Crk_C3G_to_pFRS2_pTrkA [Crk_C3G] + [pFRS2_pTrkA] ↔ [Crk_C3G_pFRS2_pTrkA];  
 
 binding_Crk_C3G_to_pFRS2_pTrkA_endo [Crk_C3G] + [pFRS2_pTrkA_endo] ↔ [Crk_C3G_pFRS2_pTrkA_endo];  
 
 binding_Grb2_SOS_pShc_to_pTrkA [Grb2_SOS_pShc] + [pTrkA] ↔ [Grb2_SOS_pShc_pTrkA];  
 
 binding_Grb2_SOS_pShc_to_pTrkA_endo [Grb2_SOS_pShc] + [pTrkA_endo] ↔ [Grb2_SOS_pShc_pTrkA_endo];  
 
 Crk_C3G_pFRS2_pTrkA_degradation [Crk_C3G_pFRS2_pTrkA] → [degradation] + [pFRS2] + [Crk_C3G];  
 
 Crk_C3G_pFRS2_pTrkA_endo_degradation [Crk_C3G_pFRS2_pTrkA_endo] → [degradation] + [Crk_C3G] + [pFRS2];  
 
 Grb2_SOS_pShc_pTrkA_degradation [Grb2_SOS_pShc_pTrkA] → [degradation] + [Grb2_SOS_pShc];  
 
 Grb2_SOS_pShc_pTrkA_endo_degradation [Grb2_SOS_pShc_pTrkA_endo] → [degradation] + [Grb2_SOS_pShc];  
 
 pFRS2_pTrkA_endo_degradation [pFRS2_pTrkA_endo] → [degradation] + [pFRS2];  
 
 form_NGFreceptor [pro_TrkA] ↔ [NGFR];  
 
 binding_Shc_to_dpEGFR_c_Cbl [Shc] + [dpEGFR_c_Cbl] ↔ [Shc_dpEGFR_c_Cbl];  
 
 binding_pShc_to_dpEGFR_c_Cbl [dpEGFR_c_Cbl] + [pShc] ↔ [pShc_dpEGFR_c_Cbl];  
 
 binding_SOS_Grb2_to_pShc_dpEGFR_c_Cbl [pShc_dpEGFR_c_Cbl] + [SOS_Grb2] ↔ [Grb2_SOS_pShc_dpEGFR_c_Cbl];  
 
 binding_c_Cbl_to_Crk_C3G_pFRS2_dpEGFR [c_Cbl] + [Crk_C3G_pFRS2_dpEGFR] ↔ [Crk_C3G_pFRS2_dpEGFR_c_Cbl];  
 
 binding_FRS2_to_dpEGFR_c_Cbl [dpEGFR_c_Cbl] + [FRS2] ↔ [FRS2_dpEGFR_c_Cbl];  
 
 binding_pFRS2_to_dpEGFR_c_Cbl [dpEGFR_c_Cbl] + [pFRS2] ↔ [pFRS2_dpEGFR_c_Cbl];  
 
 Ras_GTP_dephosphorylation [Ras_GTP] → [Ras_GDP];   {pDok_RasGAP}
 
 RAP1_GTP_dephosphorylation [Rap1_GTP] → [Rap1_GDP];   {Rap1GAP}
 
 Dok_phosphorylation [Dok] → [pDok];   {pTrkA} , {Shc_pTrkA} , {pShc_pTrkA} , {Grb2_SOS_pShc_pTrkA} , {FRS2_pTrkA} , {pFRS2_pTrkA} , {Crk_C3G_pFRS2_pTrkA}
 
 Grb1_SOS_pShc_dissociation [Grb2_SOS_pShc] → [pShc] + [pSOS_Grb2];   {dppERK}
 
 binding_MEK_to_ERK [ERK] + [MEK] ↔ [MEK_ERK];  
 
 binding_ERK_to_pMEK [ERK] + [pMEK] ↔ [pMEK_ERK];  
 
 binding_ERK_to_ppMEK [ERK] + [ppMEK] ↔ [ppMEK_ERK];  
 
 ppMEK_ERK_dissociation [ppMEK_ERK] → [ppERK] + [ppMEK];  
 
 c_Raf_Ras_GTP_dissociation [c_Raf_Ras_GTP] → [c_Raf] + [Ras_GDP];   {pDok_RasGAP}
 
 B_Raf_Ras_GTP_dissociation [B_Raf_Ras_GTP] → [B_Raf] + [Ras_GDP];   {pDok_RasGAP}
 
 B_Raf_Rap1_GTP_dissociation [B_Raf_Rap1_GTP] → [B_Raf] + [Rap1_GDP];   {Rap1GAP}
 
 J140 [c_Raf_Ras_GTP] + [MEK] → [c_Raf_Ras_GTP_MEK];  
 
 J141 [c_Raf_Ras_GTP] + [pMEK] ↔ [c_Raf_Ras_GTP_pMEK];  
 
 J142 [c_Raf_Ras_GTP] + [MEK_ERK] ↔ [c_Raf_Ras_GTP_MEK_ERK];  
 
 J143 [c_Raf_Ras_GTP] + [pMEK_ERK] ↔ [c_Raf_Ras_GTP_pMEK_ERK];  
 
 J144 [B_Raf_Ras_GTP] + [MEK] ↔ [B_Raf_Ras_GTP_MEK];  
 
 J145 [B_Raf_Ras_GTP] + [pMEK] ↔ [B_Raf_Ras_GTP_pMEK];  
 
 J146 [B_Raf_Ras_GTP] + [MEK_ERK] ↔ [B_Raf_Ras_GTP_MEK_ERK];  
 
 J147 [B_Raf_Ras_GTP] + [pMEK_ERK] ↔ [B_Raf_Ras_GTP_pMEK_ERK];  
 
 J148 [B_Raf_Rap1_GTP] + [MEK] ↔ [B_Raf_Rap1_GTP_MEK];  
 
 J149 [B_Raf_Rap1_GTP] + [pMEK] ↔ [B_Raf_Rap1_GTP_pMEK];  
 
 J150 [B_Raf_Rap1_GTP] + [MEK_ERK] ↔ [B_Raf_Rap1_GTP_MEK_ERK];  
 
 J151 [B_Raf_Rap1_GTP] + [pMEK_ERK] ↔ [B_Raf_Rap1_GTP_pMEK_ERK];  
 
 J152 [c_Raf_Ras_GTP_MEK] → [c_Raf_Ras_GTP] + [pMEK];  
 
 J153 [c_Raf_Ras_GTP_pMEK] → [c_Raf_Ras_GTP] + [ppMEK];  
 
 J154 [c_Raf_Ras_GTP_MEK_ERK] → [c_Raf_Ras_GTP] + [pMEK_ERK];  
 
 J155 [c_Raf_Ras_GTP_pMEK_ERK] → [c_Raf_Ras_GTP] + [ppMEK_ERK];  
 
 J156 [B_Raf_Ras_GTP_MEK] → [B_Raf_Ras_GTP] + [pMEK];  
 
 J157 [B_Raf_Ras_GTP_pMEK] → [B_Raf_Ras_GTP] + [ppMEK];  
 
 J158 [B_Raf_Ras_GTP_MEK_ERK] → [B_Raf_Ras_GTP] + [pMEK_ERK];  
 
 J159 [B_Raf_Ras_GTP_pMEK_ERK] → [B_Raf_Ras_GTP] + [ppMEK_ERK];  
 
 J160 [B_Raf_Rap1_GTP_MEK] → [B_Raf_Rap1_GTP] + [pMEK];  
 
 J161 [B_Raf_Rap1_GTP_pMEK] → [B_Raf_Rap1_GTP] + [ppMEK];  
 
 J162 [B_Raf_Rap1_GTP_MEK_ERK] → [B_Raf_Rap1_GTP] + [pMEK_ERK];  
 
 J163 [B_Raf_Rap1_GTP_pMEK_ERK] → [B_Raf_Rap1_GTP] + [ppMEK_ERK];  
 
 J164 [Crk_C3G_pFRS2_dpEGFR_c_Cbl_ubiq] → [c_Cbl] + [pFRS2] + [Crk_C3G];  
 
 J165 [MKP3] + [dppERK] → [dppERK_MKP3];  
 
 J166 [MKP3] + [ppERK] ↔ [ppERK_MKP3];  
 
 J167 [ppERK_MKP3] → [ERK] + [MKP3];  
 
 J168 [dppERK_MKP3] → [ppERK] + [ERK] + [MKP3];  
 
  Spatial dimensions: 3.0  Compartment size: 1.0
 
 EGFR
Compartment: compartment
Initial concentration: 0.3
 
 L_EGFR
Compartment: compartment
Initial concentration: 0.0
 
 L_EGFR_dimer
Compartment: compartment
Initial concentration: 0.0
 
 L_dpEGFR
Compartment: compartment
Initial concentration: 0.0
 
 NGFR
Compartment: compartment
Initial concentration: 0.061894
 
 pTrkA
Compartment: compartment
Initial concentration: 0.0
 
 L_NGFR
Compartment: compartment
Initial concentration: 0.0
 
 NGF
Compartment: compartment
Initial concentration: 0.0
 
 EGF
Compartment: compartment
Initial concentration: 0.001613
 
  Spatial dimensions: 3.0  Compartment size: 1.0
 
 SOS
Compartment: c1
Initial concentration: 0.1
 
 pSOS
Compartment: c1
Initial concentration: 0.0
 
 SOS_Grb2
Compartment: c1
Initial concentration: 0.0
 
 Grb2
Compartment: c1
Initial concentration: 1.0
 
 Dok
Compartment: c1
Initial concentration: 0.3
 
 pDok
Compartment: c1
Initial concentration: 0.0
 
 Crk
Compartment: c1
Initial concentration: 1.0
 
 FRS2
Compartment: c1
Initial concentration: 1.0
 
 Shc
Compartment: c1
Initial concentration: 1.0
 
 pSOS_Grb2
Compartment: c1
Initial concentration: 0.0
 
 Rap1_GDP
Compartment: c1
Initial concentration: 0.2
 
 MEK
Compartment: c1
Initial concentration: 0.68
 
 MKP3
Compartment: c1
Initial concentration: 0.018
 
 pShc_dpEGFR
Compartment: c1
Initial concentration: 0.0
 
 dpEGFR_c_Cbl
Compartment: c1
Initial concentration: 0.0
 
 B_Raf_Rap1_GTP
Compartment: c1
Initial concentration: 0.0
 
 pShc_dpEGFR_c_Cbl
Compartment: c1
Initial concentration: 0.0
 
 pFRS2_dpEGFR_c_Cbl
Compartment: c1
Initial concentration: 0.0
 
 Shc_dpEGFR
Compartment: c1
Initial concentration: 0.0
 
 c_Cbl
Compartment: c1
Initial concentration: 0.5
 
 RasGAP
Compartment: c1
Initial concentration: 0.1
 
 c_Raf
Compartment: c1
Initial concentration: 0.5
 
 B_Raf
Compartment: c1
Initial concentration: 0.2
 
 ERK
Compartment: c1
Initial concentration: 0.26
 
 PP2A
Compartment: c1
Initial concentration: 0.24
 
 Ras_GDP
Compartment: c1
Initial concentration: 0.1
 
 Rap1GAP
Compartment: c1
Initial concentration: 0.012
 
 C3G
Compartment: c1
Initial concentration: 0.5
 
 pShc
Compartment: c1
Initial concentration: 0.0
 
 pFRS2_dpEGFR
Compartment: c1
Initial concentration: 0.0
 
 pTrkA_endo
Compartment: c1
Initial concentration: 0.0
 
 MEK_ERK
Compartment: c1
Initial concentration: 0.0
 
 pMEK_ERK
Compartment: c1
Initial concentration: 0.0
 
 FRS2_dpEGFR_c_Cbl_ubiq
Compartment: c1
Initial concentration: 0.0
 
 Crk_C3G_pFRS2_dpEGFR_c_Cbl
Compartment: c1
Initial concentration: 0.0
 
 pShc_dpEGFR_c_Cbl_ubiq
Compartment: c1
Initial concentration: 0.0
 
 Crk_C3G_pFRS2_dpEGFR
Compartment: c1
Initial concentration: 0.0
 
 Grb2_SOS_pShc_dpEGFR_c_Cbl_ubiq
Compartment: c1
Initial concentration: 0.0
 
 Grb2_SOS_pShc_dpEGFR_c_Cbl
Compartment: c1
Initial concentration: 0.0
 
 Shc_dpEGFR_c_Cbl_ubiq
Compartment: c1
Initial concentration: 0.0
 
 dpEGFR_c_Cbl_ubiq
Compartment: c1
Initial concentration: 0.0
 
 proteasome
Compartment: c1
Initial concentration: 0.0
 
 Grb2_SOS_pShc
Compartment: c1
Initial concentration: 0.0
 
 Shc_dpEGFR_c_Cbl
Compartment: c1
Initial concentration: 0.0
 
 Grb2_SOS_pShc_dpEGFR
Compartment: c1
Initial concentration: 0.0
 
 pFRS2
Compartment: c1
Initial concentration: 0.0
 
 FRS2_dpEGFR
Compartment: c1
Initial concentration: 0.0
 
 pDok_RasGAP
Compartment: c1
Initial concentration: 0.0
 
 pMEK
Compartment: c1
Initial concentration: 0.0
 
 FRS2_dpEGFR_c_Cbl
Compartment: c1
Initial concentration: 0.0
 
 pFRS2_dpEGFR_c_Cbl_ubiq
Compartment: c1
Initial concentration: 0.0
 
 Ras_GTP
Compartment: c1
Initial concentration: 0.0
 
 Crk_C3G_pFRS2_dpEGFR_c_Cbl_ubiq
Compartment: c1
Initial concentration: 0.0
 
 c_Raf_Ras_GTP
Compartment: c1
Initial concentration: 0.0
 
 B_Raf_Ras_GTP
Compartment: c1
Initial concentration: 0.0
 
 ppMEK
Compartment: c1
Initial concentration: 0.0
 
 ppERK
Compartment: c1
Initial concentration: 0.0
 
 Crk_C3G
Compartment: c1
Initial concentration: 0.0
 
 Rap1_GTP
Compartment: c1
Initial concentration: 0.0
 
 ppMEK_ERK
Compartment: c1
Initial concentration: 0.0
 
 dppERK
Compartment: c1
Initial concentration: 0.0
 
 Shc_pTrkA
Compartment: c1
Initial concentration: 0.0
 
 Shc_pTrkA_endo
Compartment: c1
Initial concentration: 0.0
 
 pShc_pTrkA
Compartment: c1
Initial concentration: 0.0
 
 pFRS2_pTrkA
Compartment: c1
Initial concentration: 0.0
 
 FRS2_pTrkA
Compartment: c1
Initial concentration: 0.0
 
 pShc_pTrkA_endo
Compartment: c1
Initial concentration: 0.0
 
 FRS2_pTrkA_endo
Compartment: c1
Initial concentration: 0.0
 
 pFRS2_pTrkA_endo
Compartment: c1
Initial concentration: 0.0
 
 Crk_C3G_pFRS2_pTrkA_endo
Compartment: c1
Initial concentration: 0.0
 
 Grb2_SOS_pShc_pTrkA
Compartment: c1
Initial concentration: 0.0
 
 Crk_C3G_pFRS2_pTrkA
Compartment: c1
Initial concentration: 0.0
 
 Grb2_SOS_pShc_pTrkA_endo
Compartment: c1
Initial concentration: 0.0
 
 c_Raf_Ras_GTP_MEK
Compartment: c1
Initial concentration: 0.0
 
 c_Raf_Ras_GTP_pMEK
Compartment: c1
Initial concentration: 0.0
 
 c_Raf_Ras_GTP_MEK_ERK
Compartment: c1
Initial concentration: 0.0
 
 c_Raf_Ras_GTP_pMEK_ERK
Compartment: c1
Initial concentration: 0.0
 
 B_Raf_Ras_GTP_MEK
Compartment: c1
Initial concentration: 0.0
 
 B_Raf_Ras_GTP_pMEK
Compartment: c1
Initial concentration: 0.0
 
 B_Raf_Ras_GTP_MEK_ERK
Compartment: c1
Initial concentration: 0.0
 
 B_Raf_Ras_GTP_pMEK_ERK
Compartment: c1
Initial concentration: 0.0
 
 B_Raf_Rap1_GTP_MEK
Compartment: c1
Initial concentration: 0.0
 
 B_Raf_Rap1_GTP_pMEK
Compartment: c1
Initial concentration: 0.0
 
 B_Raf_Rap1_GTP_MEK_ERK
Compartment: c1
Initial concentration: 0.0
 
 B_Raf_Rap1_GTP_pMEK_ERK
Compartment: c1
Initial concentration: 0.0
 
 ppERK_MKP3
Compartment: c1
Initial concentration: 0.0
 
 dppERK_MKP3
Compartment: c1
Initial concentration: 0.0
 
 pro_TrkA
Compartment: c1
Initial concentration: 0.020631
 
 pro_EGFR
Compartment: c1
Initial concentration: 0.3
 
 degradation
Compartment: c1
Initial concentration: 0.0
 
form_EGFreceptor (2)
 
   re1_k1
Value: 1.0E-4
Constant
 
   re1_k2
Value: 1.0E-4
Constant
 
EGFbinding (2)
 
   re2_k1
Value: 2.2833
Constant
 
   re2_k2
Value: 0.0029666
Constant
 
dimerization (2)
 
   re8_k1
Value: 10.0
Constant
 
   re8_k2
Value: 0.02
Constant
 
binding_SOS_Grb2 (2)
 
   J3_k1
Value: 0.03
Constant
 
   J3_k2
Value: 0.0168
Constant
 
binding_pSOS_Grb2 (2)
 
   J4_k1
Value: 0.03
Constant
 
   J4_k2
Value: 0.0168
Constant
 
EGFRphosphorylation (2)
 
   J5_k1
Value: 4.0
Constant
 
   J5_k2
Value: 0.0010
Constant
 
binding_cCbI_dpEGFR (2)
 
   J6_k1
Value: 0.5
Constant
 
   J6_k2
Value: 0.2
Constant
 
binding_pShc_LdpEGFR (2)
 
   J7_k1
Value: 10.0
Constant
 
   J7_k2
Value: 0.2
Constant
 
pDOKdephosphorylation (2)
 
   J8_k1
Value: 0.0020
Constant
 
   J8_k2
Value: 1.0E-5
Constant
 
binding_cCbl_pShc_dpEGFR (2)
 
   J9_k1
Value: 0.5
Constant
 
   J9_k2
Value: 0.2
Constant
 
SOSdephosphorylation (1)
 
   J10_k
Value: 0.0020
Constant
 
pSOS_Grb2_dephosphorylation (1)
 
   J11_k
Value: 0.0020
Constant
 
binding_Shc_LdpEGFR (2)
 
   J12_k1
Value: 10.0
Constant
 
   J12_k2
Value: 0.2
Constant
 
Shc_dpEGFR_phosphorylation (1)
 
   J13_k
Value: 1.0
Constant
 
dpEGFR_c_Cbl_ubiquitination (1)
 
   J14_k
Value: 0.05
Constant
 
dpEGFR_cCbl_degrad (1)
 
   J15_k
Value: 0.0010
Constant
 
binding_cCbl_Shc_dpEGFR (2)
 
   J16_k1
Value: 0.5
Constant
 
   J16_k2
Value: 0.2
Constant
 
Shc_dpEGFR_c_CBl_Ubiquitination (1)
 
   J17_k
Value: 0.05
Constant
 
Shc_dpEGFR_c_Cbl_ubiq_Degradation (1)
 
   J18_k
Value: 0.0010
Constant
 
pShc_dpEGFR_c_Cbl_ubiquitination (1)
 
   J19_k
Value: 0.05
Constant
 
pShc_dpEGFR_c_Cbl_ubiq_degradation (1)
 
   J20_k
Value: 0.0010
Constant
 
Shc_dpEGFR_c_Cblphosphorylation (1)
 
   J21_k
Value: 1.0
Constant
 
binding_Grb2_SOS_pShc (2)
 
   J22_k1
Value: 10.0
Constant
 
   J22_k2
Value: 0.2
Constant
 
binding_Grb2_SOS_pShc_dpEGFR (2)
 
   J23_k1
Value: 10.0
Constant
 
   J23_k2
Value: 0.2
Constant
 
binding_Grb2_SOS_pShc_dpEGFR (2)
 
   J24_k1
Value: 10.0
Constant
 
   J24_k2
Value: 0.2
Constant
 
binding_c_Cbl_Grb2_SOS_pShc_dpEGFR (2)
 
   J25_k1
Value: 0.5
Constant
 
   J25_k2
Value: 0.2
Constant
 
binding_Grb2_SOS_pShc_to_dpEGFR_c_Cbl (2)
 
   J27_k1
Value: 10.0
Constant
 
   J27_k2
Value: 0.2
Constant
 
Grb2_SOS_pShc_dpEGFR_c_Cbl_ubiquitination (1)
 
   J28_k
Value: 0.05
Constant
 
Grb2_SOS_pShc_dpEGFR_c_Cbl_ubiq_degradation (1)
 
   J29_k
Value: 0.0010
Constant
 
Grb2_SOS_pShc_Dissociation (1)
 
   J30_k
Value: 0.0050
Constant
 
J31 (2)
 
   J31_Vmax
Value: 0.2
Constant
 
   J31_Km1
Value: 0.1
Constant
 
pShc_dephosphorylation (1)
 
   J32_k
Value: 0.0050
Constant
 
pFRS2_dephosphorylation (1)
 
   J33_k
Value: 0.0050
Constant
 
binding_Crk_to_C3G (2)
 
   J34_k1
Value: 1.0
Constant
 
   J34_k2
Value: 0.0020
Constant
 
binding_L_dpEGFR_to_FRS2 (2)
 
   J35_k1
Value: 1.0
Constant
 
   J35_k2
Value: 0.2
Constant
 
binding_pFRS2_to_L_dpEGFR (2)
 
   J36_k1
Value: 1.0
Constant
 
   J36_k2
Value: 0.2
Constant
 
FRS2_dpEGFRphsphorylation (1)
 
   J37_k
Value: 1.0
Constant
 
binding_Crk_C3G_to_pFRS2_pRTK (2)
 
   J38_k1
Value: 1.0
Constant
 
   J38_k2
Value: 0.2
Constant
 
binding_c_Cbl_to_FRS2_dpEGFR (2)
 
   J39_k1
Value: 0.5
Constant
 
   J39_k2
Value: 0.2
Constant
 
binding_c_Cbl_to_pFRS2_dpEGFR (2)
 
   J40_k1
Value: 0.5
Constant
 
   J40_k2
Value: 0.2
Constant
 
pFRS2_dpEGFR_c_Cbl_ubiquitiation (1)
 
   J41_k
Value: 0.05
Constant
 
FRS2_dpEGFR_c_Cbl_ubiquitination (1)
 
   J42_k
Value: 0.05
Constant
 
FRS2_dpEGFR_c_Cbl_phosphorylation (1)
 
   J43_k
Value: 1.0
Constant
 
binding_Crk_C3G_to_pFRS2_pFRS2_dpEGFR_c_Cbl (2)
 
   J44_k1
Value: 1.0
Constant
 
   J44_k2
Value: 0.2
Constant
 
Crk_C3G_pFRS2_dpEGFR_c_Cbl_ubiquitination (1)
 
   J45_k
Value: 0.05
Constant
 
FRS2_dpEGFR_c_Cbl_ubiq_dissociation (1)
 
   J46_k
Value: 0.0010
Constant
 
pFRS2_dpEGFR_c_Cbl_ubiq_dissociation (1)
 
   J47_k
Value: 0.0010
Constant
 
binding_RasGAP_to_pDOK (2)
 
   J49_k1
Value: 0.12
Constant
 
   J49_k2
Value: 0.01
Constant
 
SOS_Grb2_phosphorylation (2)
 
   J50_Vmax
Value: 1.0
Constant
 
   J50_Km1
Value: 25.641
Constant
 
SOS_phosphorylation (2)
 
   J51_Vmax
Value: 1.0
Constant
 
   J51_Km1
Value: 25.641
Constant
 
binding_c_Raf_to_Ras_GTP (2)
 
   J52_k1
Value: 60.0
Constant
 
   J52_k2
Value: 0.5
Constant
 
binding_B_Raf_to_Rap1_GTP (2)
 
   J53_k1
Value: 60.0
Constant
 
   J53_k2
Value: 0.5
Constant
 
binding_B_Raf_to_Ras_GTP (2)
 
   J54_k1
Value: 60.0
Constant
 
   J54_k2
Value: 0.5
Constant
 
ppMEK_dephosphorylation (2)
 
   J57_Vmax
Value: 3.0
Constant
 
   J57_Km1
Value: 15.657
Constant
 
pMEK_dephosphorylation (2)
 
   J58_Vmax
Value: 3.0
Constant
 
   J58_Km1
Value: 15.657
Constant
 
ppMEK_ERK (2)
 
   J61_Vmax
Value: 3.0
Constant
 
   J61_Km1
Value: 15.657
Constant
 
pMEK_ERK_dephosphorylation (2)
 
   J62_Vmax
Value: 3.0
Constant
 
   J62_Km1
Value: 15.657
Constant
 
ppERK_dimerization (2)
 
   J63_k1
Value: 10.0
Constant
 
   J63_k2
Value: 0.075
Constant
 
Ras_GTP_dephosphorylation (1)
 
   J66_k
Value: 1.667E-4
Constant
 
Rap1_GTP_dephosphorylation (1)
 
   J67_k
Value: 1.166E-4
Constant
 
Rap1_GTP_phosphorylation (2)
 
   J68_Vmax
Value: 0.024
Constant
 
   J68_Km1
Value: 0.01
Constant
 
Ras_GDP_phosphorylation (2)
 
   J69_Vmax
Value: 2.0
Constant
 
   J69_Km1
Value: 0.02
Constant
 
binding_NGF_to_NGFR (2)
 
   J70_k1
Value: 6.2
Constant
 
   J70_k2
Value: 6.4E-5
Constant
 
TrkA_phosphorylation (1)
 
   J71_k
Value: 1.0
Constant
 
pTrkA_intermalization (1)
 
   J72_k
Value: 6.3E-4
Constant
 
pTrkA_endo_degradation (1)
 
   J73_k
Value: 4.2E-4
Constant
 
pTrkA_degradation (1)
 
   J74_k
Value: 0.0022
Constant
 
binding_Shc_to_pTrkA (2)
 
   J75_k1
Value: 10.0
Constant
 
   J75_k2
Value: 0.2
Constant
 
binding_pShc_to_pTrkA (2)
 
   J76_k1
Value: 10.0
Constant
 
   J76_k2
Value: 0.2
Constant
 
binding_FRS2_to_pTrkA (2)
 
   J77_k1
Value: 5.0
Constant
 
   J77_k2
Value: 0.1
Constant
 
binding_pFRS2_to_pTrkA (2)
 
   J78_k1
Value: 5.0
Constant
 
   J78_k2
Value: 0.1
Constant
 
binding_Shc_to_pTrkA_endo (2)
 
   J79_k1
Value: 10.0
Constant
 
   J79_k2
Value: 0.2
Constant
 
binding_pShc_to_pTrkA_endo (2)
 
   J80_k1
Value: 10.0
Constant
 
   J80_k2
Value: 0.2
Constant
 
Shc_pTrkA_endo_phosphorylation (1)
 
   J81_k
Value: 0.1
Constant
 
Shc_pTrkA_phosphorylation (1)
 
   J82_k
Value: 0.1
Constant
 
pFRS2_pTrkA_phosphorylation (1)
 
   J83_k
Value: 2.0
Constant
 
binding_FRS2_to_pTrkA_endo (2)
 
   J84_k1
Value: 5.0
Constant
 
   J84_k2
Value: 0.1
Constant
 
binding_pFRS2_to_pTrkA_endo (2)
 
   J85_k1
Value: 5.0
Constant
 
   J85_k2
Value: 0.1
Constant
 
FRS2_pTrkA_endo_phosphorylation (1)
 
   J86_k
Value: 2.0
Constant
 
FRS2_pTrkA_degradation (1)
 
   J87_k
Value: 0.0022
Constant
 
pFRS2_pTrkA_degradation (1)
 
   J88_k
Value: 0.0022
Constant
 
Shc_pTrkA_degradation (1)
 
   J89_k
Value: 0.0022
Constant
 
pShc_pTrkA_degradation (1)
 
   J90_k
Value: 0.0022
Constant
 
FRS2_pTrkA_endo_degradation (1)
 
   J92_k
Value: 4.2E-4
Constant
 
Shc_pTrkA_endo_degradation (1)
 
   J93_k
Value: 4.2E-4
Constant
 
pShc_pTrkA_endo_degradation (1)
 
   J94_k
Value: 4.2E-4
Constant
 
binding_Grb2_SOS_to_pShc_pTrkA_endo (2)
 
   J95_k1
Value: 10.0
Constant
 
   J95_k2
Value: 0.2
Constant
 
binding_Grb2_SOS_to_pShc_pTrkA (2)
 
   J96_k1
Value: 10.0
Constant
 
   J96_k2
Value: 0.2
Constant
 
Grb2_SOS_pShc_pTrkA_ubiquitination (1)
 
   J97_k
Value: 6.3E-4
Constant
 
Crk_C3G_pFRS2_pTrkA_ubiquitination (1)
 
   J98_k
Value: 6.3E-4
Constant
 
pFRS2_pTrkA_ubiquitination (1)
 
   J99_k
Value: 6.3E-4
Constant
 
FRS2_pTrkA_ubiquitination (1)
 
   J100_k
Value: 6.3E-4
Constant
 
pShc_pTrkA_ubiquitination (1)
 
   J101_k
Value: 6.3E-4
Constant
 
Shc_pTrkA_ubiquitination (1)
 
   J102_k
Value: 6.3E-4
Constant
 
binding_Crk_C3G_to_pFRS2_pTrkA (2)
 
   J103_k1
Value: 1.0
Constant
 
   J103_k2
Value: 0.2
Constant
 
binding_Crk_C3G_to_pFRS2_pTrkA_endo (2)
 
   J104_k1
Value: 1.0
Constant
 
   J104_k2
Value: 0.2
Constant
 
binding_Grb2_SOS_pShc_to_pTrkA (2)
 
   J105_k1
Value: 10.0
Constant
 
   J105_k2
Value: 0.2
Constant
 
binding_Grb2_SOS_pShc_to_pTrkA_endo (2)
 
   J106_k1
Value: 10.0
Constant
 
   J106_k2
Value: 0.2
Constant
 
Crk_C3G_pFRS2_pTrkA_degradation (1)
 
   J107_k
Value: 0.0022
Constant
 
Crk_C3G_pFRS2_pTrkA_endo_degradation (1)
 
   J108_k
Value: 4.2E-4
Constant
 
Grb2_SOS_pShc_pTrkA_degradation (1)
 
   J109_k
Value: 0.0022
Constant
 
Grb2_SOS_pShc_pTrkA_endo_degradation (1)
 
   J110_k
Value: 4.2E-4
Constant
 
pFRS2_pTrkA_endo_degradation (1)
 
   J112_k
Value: 4.2E-4
Constant
 
form_NGFreceptor (2)
 
   J113_k1
Value: 8.333E-4
Constant
 
   J113_k2
Value: 2.7778E-4
Constant
 
binding_Shc_to_dpEGFR_c_Cbl (2)
 
   J115_k1
Value: 10.0
Constant
 
   J115_k2
Value: 0.2
Constant
 
binding_pShc_to_dpEGFR_c_Cbl (2)
 
   J116_k1
Value: 10.0
Constant
 
   J116_k2
Value: 0.2
Constant
 
binding_SOS_Grb2_to_pShc_dpEGFR_c_Cbl (2)
 
   J117_k1
Value: 10.0
Constant
 
   J117_k2
Value: 0.2
Constant
 
binding_c_Cbl_to_Crk_C3G_pFRS2_dpEGFR (2)
 
   J119_k1
Value: 0.5
Constant
 
   J119_k2
Value: 0.2
Constant
 
binding_FRS2_to_dpEGFR_c_Cbl (2)
 
   J118_k1
Value: 1.0
Constant
 
   J118_k2
Value: 0.2
Constant
 
binding_pFRS2_to_dpEGFR_c_Cbl (2)
 
   J120_k1
Value: 1.0
Constant
 
   J120_k2
Value: 0.2
Constant
 
Ras_GTP_dephosphorylation (2)
 
   J121_Vmax
Value: 10.0
Constant
 
   J121_Km1
Value: 1.0
Constant
 
RAP1_GTP_dephosphorylation (2)
 
   J122_Vmax
Value: 2.0
Constant
 
   J122_Km1
Value: 1.0
Constant
 
Dok_phosphorylation (2)
 
   J123_Vmax
Value: 0.02
Constant
 
   J123_Km1
Value: 0.1
Constant
 
Grb1_SOS_pShc_dissociation (2)
 
   J124_Vmax
Value: 1.0
Constant
 
   J124_Km1
Value: 25.641
Constant
 
binding_MEK_to_ERK (2)
 
   J133_k1
Value: 16.304
Constant
 
   J133_k2
Value: 0.6
Constant
 
binding_ERK_to_pMEK (2)
 
   J134_k1
Value: 16.304
Constant
 
   J134_k2
Value: 0.6
Constant
 
binding_ERK_to_ppMEK (2)
 
   J135_k1
Value: 16.304
Constant
 
   J135_k2
Value: 0.6
Constant
 
ppMEK_ERK_dissociation (1)
 
   J136_k
Value: 0.15
Constant
 
c_Raf_Ras_GTP_dissociation (2)
 
   J137_Vmax
Value: 10.0
Constant
 
   J137_Km1
Value: 1.0
Constant
 
B_Raf_Ras_GTP_dissociation (2)
 
   J138_Vmax
Value: 10.0
Constant
 
   J138_Km1
Value: 1.0
Constant
 
B_Raf_Rap1_GTP_dissociation (2)
 
   J139_Vmax
Value: 2.0
Constant
 
   J139_Km1
Value: 1.0
Constant
 
J140 (2)
 
   J140_k1
Value: 15.625
Constant
 
   J140_k2
Value: 2.0
Constant
 
J141 (2)
 
   J141_k1
Value: 15.625
Constant
 
   J141_k2
Value: 2.0
Constant
 
J142 (2)
 
   J142_k1
Value: 15.625
Constant
 
   J142_k2
Value: 2.0
Constant
 
J143 (2)
 
   J143_k1
Value: 15.625
Constant
 
   J143_k2
Value: 2.0
Constant
 
J144 (2)
 
   J144_k1
Value: 6.25
Constant
 
   J144_k2
Value: 0.8
Constant
 
J145 (2)
 
   J145_k1
Value: 6.25
Constant
 
   J145_k2
Value: 0.8
Constant
 
J146 (2)
 
   J146_k1
Value: 6.25
Constant
 
   J146_k2
Value: 0.8
Constant
 
J147 (2)
 
   J147_k1
Value: 6.25
Constant
 
   J147_k2
Value: 0.8
Constant
 
J148 (2)
 
   J148_k1
Value: 9.375
Constant
 
   J148_k2
Value: 1.2
Constant
 
J149 (2)
 
   J149_k1
Value: 9.375
Constant
 
   J149_k2
Value: 1.2
Constant
 
J150 (2)
 
   J150_k1
Value: 9.375
Constant
 
   J150_k2
Value: 1.2
Constant
 
J151 (2)
 
   J151_k1
Value: 9.375
Constant
 
   J151_k2
Value: 1.2
Constant
 
J152 (1)
 
   J152_k
Value: 0.5
Constant
 
J153 (1)
 
   J153_k
Value: 0.5
Constant
 
J154 (1)
 
   J154_k
Value: 0.5
Constant
 
J155 (1)
 
   J155_k
Value: 0.5
Constant
 
J156 (1)
 
   J156_k
Value: 0.2
Constant
 
J157 (1)
 
   J157_k
Value: 0.2
Constant
 
J158 (1)
 
   J158_k
Value: 0.2
Constant
 
J159 (1)
 
   J159_k
Value: 0.2
Constant
 
J160 (1)
 
   J160_k
Value: 0.3
Constant
 
J161 (1)
 
   J161_k
Value: 0.3
Constant
 
J162 (1)
 
   J162_k
Value: 0.3
Constant
 
J163 (1)
 
   J163_k
Value: 0.3
Constant
 
J164 (1)
 
   J164_k
Value: 0.0010
Constant
 
J165 (2)
 
   J165_k1
Value: 15.0
Constant
 
   J165_k2
Value: 0.24
Constant
 
J166 (2)
 
   J166_k1
Value: 15.0
Constant
 
   J166_k2
Value: 0.24
Constant
 
J167 (1)
 
   J167_k
Value: 0.06
Constant
 
J168 (1)
 
   J168_k
Value: 0.06
Constant
 
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