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BIOMD0000000175 - Birtwistle2007_ErbB_Signalling

 

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Reference Publication
Publication ID: 18004277
Birtwistle MR, Hatakeyama M, Yumoto N, Ogunnaike BA, Hoek JB, Kholodenko BN.
Ligand-dependent responses of the ErbB signaling network: experimental and modeling analyses.
Mol. Syst. Biol. 2007; 3: 144
Department of Chemical Engineering, University of Delaware, Newark, DE, USA.  [more]
Model
Original Model: BIOMD0000000175.xml.origin
Submitter: Molecular Systems Biology
Submission ID: MODEL5563731079
Submission Date: 18 Jul 2008 13:45:02 UTC
Last Modification Date: 07 Apr 2014 00:23:04 UTC
Creation Date: 17 Jul 2008 13:46:08 UTC
Encoders:  Lukas Endler
set #1
bqbiol:hasTaxon Taxonomy Homo sapiens
bqbiol:hasVersion Reactome REACT_12058.1
Gene Ontology MAPK cascade
set #2
bqbiol:isVersionOf Gene Ontology ERBB signaling pathway
Notes

This model originates from BioModels Database: A Database of Annotated Published Models. It is copyright (c) 2005-2009 The BioModels Team.
For more information see the terms of use.
To cite BioModels Database, please use Le Novère N., Bornstein B., Broicher A., Courtot M., Donizelli M., Dharuri H., Li L., Sauro H., Schilstra M., Shapiro B., Snoep J.L., Hucka M. (2006) BioModels Database: A Free, Centralized Database of Curated, Published, Quantitative Kinetic Models of Biochemical and Cellular Systems Nucleic Acids Res., 34: D689-D691.

Model
Publication ID: 18004277 Submission Date: 18 Jul 2008 13:45:02 UTC Last Modification Date: 07 Apr 2014 00:23:04 UTC Creation Date: 17 Jul 2008 13:46:08 UTC
Mathematical expressions
Reactions
EGF Binding to ErbB1 HRG Binding to ErbB3 HRG Binding to ErbB4 ErbB1 Dimerization
ErbB1/ErbB2 Heterodimerization ErbB2/ErbB3 Heterodimerization ErbB3/ErbB4 Heterodimerization ErbB2/ErbB4 Heterodimerization
ErbB4 Homodimerization Net E11 Phosphorylation Net E12 Phosphorylation Net E23 Phosphorylation
Net E34 Phosphorylation Net E24 Phosphorylation Net E44 Phosphorylation Net E11P/Grb2 binding
Net E11P/Shc binding Net E11P/RasGAP binding Net E12P/Grb2 binding Net E12P/Shc binding
Net E12P/RasGAP binding Net E23P/Grb2 binding Net E23P/Shc binding Net E23P/PI3K binding
Net E23P/RasGAP binding Net E34P/Grb2 binding Net E34P/Shc binding Net E34P/PI3K binding
Net E34P/RasGAP binding Net E24P/Grb2 binding Net E24P/Shc binding Net E24P/PI3K binding
Net E24P/RasGAP binding Net E44P/RasGAP binding Net E44P/Shc binding Net E44P/PI3K binding
Net E44P/RasGAP binding Net Shc Phosphorylation Net Gab1 Phosphorylation Net Grb2/SOS binding
Net Grb2/Gab1 binding Net Shc/Grb2 binding Net Gab1/Shc binding Net Gab1/PI3K binding
Net Gab1/RasGAP binding Net Gab1/PIP3 binding Net Akt Activation Net PIP3 Production
Net RasGTP Production Net RasGAP Phosphorylation Net Raf Activation Net MEK Activation
Net SOS S/T Phosphorylation Net Gab1 S/T Phosphorylation Grb2 binding to P3_A SOS binding to SigA-G
Gab1 binding to SigG-O SOS binding to SigG-A ErbB1/ErbB3 Heterodimerization ErbB1/ErbB4 Heterodimerization
Net E13 Phosphorylation Net E14 Phosphorylation Net E13/Grb2 Binding Net E13/Shc Binding
Net E13/PI3K Binding Net E13/RasGAP Binding Net E14/Grb2 Binding Net E14/Shc Binding
Net E14/PI3K Binding Net E14/RasGAP Binding Net E11/PTP1B Binding Net E12/PTP1B Binding
Net E23/PTP1B Binding Net E34/PTP1B Binding Net E24/PTP1B Binding Net E44/PTP1B Binding
Net E13/PTP1B Binding Net E14/PTP1B Binding Net E1 S/T Phosphorylation Net E2 S/T Phosphorylation
Net E4 S/T Phosphorylation Net E_E1 S/T Phosphorylation Net H_E4 S/T Phosphorylation EGF binding to E1-PT
HRG binding to E4-PT PTP1B binding to SigAP E11P Degradation E11G Degradation
E11S Degradation E11R Degradation E11T Degradation 1-1 Dimer Internalization Fraction
EGF in EC compartment HRG in EC compartment ERK binding to MEKstar pERK production
ERK binding to MEKstar ERKstar production ERKstar binding to Phosphatase ERKstar dephosphorylation
pERK binding to Phosphatase pERK dephosphorylation    
Rules
Assignment Rule (variable: normalized Akt*) Assignment Rule (variable: normalized Erk*)    
Physical entities
Compartments Species
membrane ErbB1 ErbB2 ErbB3
ErbB4 EGF-ErbB1 HRG-ErbB3
HRG-ErbB4 (EGF-ErbB1)2 EGF-ErbB1-ErbB2
HRG-ErbB3-ErbB2 (HRG-ErbB3/4)2 HRG-Erb4-ErbB2
(HRG-Erb4)2 E11_p E12_p
E23_p E34_p E24_p
E44_p Grb2 Shc
PI-3K RasGAP SOS
Gab1 E11-Grb2 E11-Shc
E11-RasGAP E12-Grb2 E12-Shc
E12-RasGAP E23-Grb2 E23-Shc
E23-PI-3K E23-RasGAP E34-Grb2
E34-Shc E34-PI-3K E34-RasGAP
E24-Grb2 E24-Shc E24-PI-3K
E24-RasGAP E44-Grb2 E44-Shc
E44-PI-3K E44-RasGAP Sum Grb2
Sum Shc Sum PI-3K Sum RasGAP
Sum Gab1 Sum Shc_p Sum Gab1_p
Sum Grb2-SOS Sum Grb2-Gab1 Sum Shc_p-Grb2
Sum Gab1_p-Shc Sum Gab1_p-PI-3K Sum Gab1_p-RasGAP
Empty PIP3-Gab1 PIP2
PIP3 Akt RasGDP
RasGTP Sum RasGAP_p Raf
Raf* MEK MEK*
ERK ERK* SOS_p
Gab1_p Gab1_SumGrb2-SOS Sum PIP3-Gab1-Grb2
Sum PIP3-Gab1-Grb2_SOS Sum SOS ErbB1-ErbB3
ErbB1-ErbB4 ErbB1-ErbB3_p ErbB1-ErbB3_p
E13-Grb2 E13-Shc E13-PI-3K
E13-RasGAP E14-Grb2 E14-Shc
E14-PI-3K E14-RasGAP PTP-1B
E11-PTP-1B E12-PTP-1B E23-PTP-1B
E34-PTP-1B E24-PTP-1B E44-PTP-1B
E13-PTP-1B E14-PTP-1B Sig-PTP-1B
E1_p-PTP-1B E2_p-PTP-1B E4_p-PTP-1B
E_E1_p-PTP-1B H_E4_p-PTP-1B Aktstar
SumGab1_p-PTP-1B EGF HRG
fint p_ERK ERK-MEK*
p_ERK-MEK* p_ERK-ERKpase ERKpase
ERK*-ERKpase normalized Akt* normalized Erk*
Global parameters
ErbB1_Abund ErbB2_Abund ErbB3_Abund ErbB4_Abund
Grb2_Abund Shc_Abund PI3K_Abund RasGAP_Abund
SOS_Abund Gab1_Abund PIP2_Abund Akt_Abund
Ras_Abund Raf_Abund MEK_Abund ERK_Abund
VmaxPY KmPY kdeg kf47
Vmaxr47 Kmf47 Kmr47 kf48
Kmf48 Kmr48 PTEN kf49
kr49 Kmf49 Kmr49 Kmr49b
kr49b kf51 kr51 Vmaxr51
Kmf51 Kmr51 Kmrb51 kf52
Vmaxr52 Kmf52 Kmr52 kf53
Vmaxr53 Kmf53 Kmr53 kf54
Vmaxr54 Kmf54 Kmr54 kf55
Vmaxr55 Kmf55 Kmr55 kf38
kf39 kf50 a98 b98
koff46 EGF_off HRGoff_3 HRGoff_4
koff4 koff5 koff6 koff7
koff8 koff9 koff57 koff16
koff17 koff18 koff19 koff20
koff21 koff22 koff23 koff24
koff25 koff26 koff27 koff28
koff29 koff30 koff31 koff32
koff33 koff34 koff35 koff36
koff37 koff65 koff66 koff67
koff40 koff41 koff42 koff43
koff44 koff45 koff58 koff59
koff68 PTP1B_Abund kPTP10 kPTP11
kPTP12 kPTP13 kPTP14 kPTP15
kPTP63 kPTP64 koff73 koff74
koff75 koff76 koff77 koff78
koff79 koff80 kPTP38 kPTP39
koff88 kPTP50 kf81 Vmaxr81
Kmf81 Kmr81 kf82 Vmaxr82
Kmf82 Kmr82 kf83 Vmaxr83
Kmf83 Kmr83 kf84 Vmaxr84
Kmf84 Kmr84 kf85 Vmaxr85
Kmf85 Kmr85 kcon49 kon1
kon86 kon2 kon3 kon87
kon4 kon5 kon6 kon7
kon8 kon9 kon57 kf10
kf11 kf12 kf13 kf14
kf15 kf63 kf64 kon16
kon17 kon18 kon73 kon19
kon20 kon21 kon74 kon22
kon23 kon24 kon25 kon75
kon26 kon27 kon28 kon29
kon76 kon30 kon31 kon32
kon33 kon77 kon34 kon35
kon36 kon37 kon78 kon79
kon65 kon66 kon67 kon80
kon40 kon41 kon42 kon43
kon44 kon45 kon88 kon46
kon58 kon59 kon60 VeVc
koff60 koff61 kon61 kon62
koff62 kon68 kon69 koff69
kon70 koff70 kon71 koff71
kon72 koff72 eps kon89
koff89 kcat90 kon91 koff91
kcat92 kon93 koff93 kcat94
kon95 koff95 kcat96 ERKPpase_Abund
Reactions (102)
 
 EGF Binding to ErbB1 [ErbB1] ↔ [EGF-ErbB1];   {EGF}
 
 HRG Binding to ErbB3 [ErbB3] ↔ [HRG-ErbB3];   {HRG}
 
 HRG Binding to ErbB4 [ErbB4] ↔ [HRG-ErbB4];   {HRG}
 
 ErbB1 Dimerization [EGF-ErbB1] + [EGF-ErbB1] ↔ [(EGF-ErbB1)2];  
 
 ErbB1/ErbB2 Heterodimerization [EGF-ErbB1] + [ErbB2] ↔ [EGF-ErbB1-ErbB2];  
 
 ErbB2/ErbB3 Heterodimerization [HRG-ErbB3] + [ErbB2] ↔ [HRG-ErbB3-ErbB2];  
 
 ErbB3/ErbB4 Heterodimerization [HRG-ErbB3] + [HRG-ErbB4] ↔ [(HRG-ErbB3/4)2];  
 
 ErbB2/ErbB4 Heterodimerization [HRG-ErbB4] + [ErbB2] ↔ [HRG-Erb4-ErbB2];  
 
 ErbB4 Homodimerization [HRG-ErbB4] + [HRG-ErbB4] ↔ [(HRG-Erb4)2];  
 
 Net E11 Phosphorylation [(EGF-ErbB1)2] ↔ [E11_p];   {Sig-PTP-1B}
 
 Net E12 Phosphorylation [EGF-ErbB1-ErbB2] ↔ [E12_p];   {Sig-PTP-1B}
 
 Net E23 Phosphorylation [HRG-ErbB3-ErbB2] ↔ [E23_p];   {Sig-PTP-1B}
 
 Net E34 Phosphorylation [(HRG-ErbB3/4)2] ↔ [E34_p];   {Sig-PTP-1B}
 
 Net E24 Phosphorylation [HRG-Erb4-ErbB2] ↔ [E24_p];   {Sig-PTP-1B}
 
 Net E44 Phosphorylation [(HRG-Erb4)2] ↔ [E44_p];   {Sig-PTP-1B}
 
 Net E11P/Grb2 binding [E11_p] + [Grb2] ↔ [E11-Grb2] + [Sum Grb2];   {Sum Grb2-Gab1} , {Sum Grb2-SOS} , {Gab1_SumGrb2-SOS}
 
 Net E11P/Shc binding [E11_p] + [Shc] ↔ [E11-Shc] + [Sum Shc];   {Sum Shc_p} , {Sum Shc_p-Grb2}
 
 Net E11P/RasGAP binding [E11_p] + [RasGAP] ↔ [E11-RasGAP] + [Sum RasGAP];   {Sum RasGAP_p}
 
 Net E12P/Grb2 binding [E12_p] + [Grb2] ↔ [E12-Grb2] + [Sum Grb2];   {Sum Grb2-Gab1} , {Sum Grb2-SOS} , {Gab1_SumGrb2-SOS}
 
 Net E12P/Shc binding [E12_p] + [Shc] ↔ [E12-Shc] + [Sum Shc];   {Sum Shc_p} , {Sum Shc_p-Grb2}
 
 Net E12P/RasGAP binding [E12_p] + [RasGAP] ↔ [E12-RasGAP] + [Sum RasGAP];   {Sum RasGAP_p}
 
 Net E23P/Grb2 binding [E23_p] + [Grb2] ↔ [E23-Grb2] + [Sum Grb2];   {Sum Grb2-Gab1} , {Sum Grb2-SOS} , {Gab1_SumGrb2-SOS}
 
 Net E23P/Shc binding [E23_p] + [Shc] ↔ [E23-Shc] + [Sum Shc];   {Sum Shc_p} , {Sum Shc_p-Grb2}
 
 Net E23P/PI3K binding [E23_p] + [PI-3K] ↔ [E23-PI-3K] + [Sum PI-3K];  
 
 Net E23P/RasGAP binding [E23_p] + [RasGAP] ↔ [E23-RasGAP] + [Sum RasGAP];   {Sum RasGAP_p}
 
 Net E34P/Grb2 binding [E34_p] + [Grb2] ↔ [E34-Grb2] + [Sum Grb2];   {Sum Grb2-Gab1} , {Sum Grb2-SOS} , {Gab1_SumGrb2-SOS}
 
 Net E34P/Shc binding [E34_p] + [Shc] ↔ [E34-Shc] + [Sum Shc];   {Sum Shc_p} , {Sum Shc_p-Grb2}
 
 Net E34P/PI3K binding [E34_p] + [PI-3K] ↔ [E34-PI-3K] + [Sum PI-3K];  
 
 Net E34P/RasGAP binding [E34_p] + [RasGAP] ↔ [E34-RasGAP] + [Sum RasGAP];   {Sum RasGAP_p}
 
 Net E24P/Grb2 binding [E24_p] + [Grb2] ↔ [E24-Grb2] + [Sum Grb2];   {Sum Grb2-Gab1} , {Sum Grb2-SOS} , {Gab1_SumGrb2-SOS}
 
 Net E24P/Shc binding [E24_p] + [Shc] ↔ [E24-Shc] + [Sum Shc];   {Sum Shc_p} , {Sum Shc_p-Grb2}
 
 Net E24P/PI3K binding [E24_p] + [PI-3K] ↔ [E24-PI-3K] + [Sum PI-3K];  
 
 Net E24P/RasGAP binding [E24_p] + [RasGAP] ↔ [E24-RasGAP] + [Sum RasGAP];   {Sum RasGAP_p}
 
 Net E44P/RasGAP binding [E44_p] + [Grb2] ↔ [E44-Grb2] + [Sum Grb2];   {Sum Grb2-Gab1} , {Sum Grb2-SOS} , {Gab1_SumGrb2-SOS}
 
 Net E44P/Shc binding [E44_p] + [Shc] ↔ [E44-Shc] + [Sum Shc];   {Sum Shc_p} , {Sum Shc_p-Grb2}
 
 Net E44P/PI3K binding [E44_p] + [PI-3K] ↔ [E44-PI-3K] + [Sum PI-3K];  
 
 Net E44P/RasGAP binding [E44_p] + [RasGAP] ↔ [E44-RasGAP] + [Sum RasGAP];   {Sum RasGAP_p}
 
 Net Shc Phosphorylation [Sum Shc] ↔ [Sum Shc_p];   {E11_p} , {E12_p} , {E23_p} , {E24_p} , {E34_p} , {E44_p} , {ErbB1-ErbB3_p} , {ErbB1-ErbB3_p} , {Sig-PTP-1B}
 
 Net Gab1 Phosphorylation [Sum Gab1] ↔ [Sum Gab1_p];   {E11_p} , {E12_p} , {E23_p} , {E24_p} , {E34_p} , {E44_p} , {ErbB1-ErbB3_p} , {ErbB1-ErbB3_p} , {Sig-PTP-1B}
 
 Net Grb2/SOS binding [Sum Grb2] + [SOS] ↔ [Sum Grb2-SOS] + [Sum SOS];  
 
 Net Grb2/Gab1 binding [Sum Grb2] + [Gab1] ↔ [Sum Grb2-Gab1] + [Sum Gab1];   {Sum Gab1_p} , {Sum Gab1_p-Shc} , {Sum Gab1_p-RasGAP} , {Sum Gab1_p-PI-3K} , {SumGab1_p-PTP-1B}
 
 Net Shc/Grb2 binding [Sum Shc_p] + [Grb2] ↔ [Sum Shc_p-Grb2] + [Sum Grb2];   {Sum Grb2-Gab1} , {Sum Grb2-SOS} , {Gab1_SumGrb2-SOS}
 
 Net Gab1/Shc binding [Sum Gab1_p] + [Shc] ↔ [Sum Gab1_p-Shc] + [Sum Shc];   {Sum Shc_p} , {Sum Shc_p-Grb2}
 
 Net Gab1/PI3K binding [Sum Gab1_p] + [PI-3K] ↔ [Sum Gab1_p-PI-3K] + [Sum PI-3K];  
 
 Net Gab1/RasGAP binding [Sum Gab1_p] + [RasGAP] ↔ [Sum Gab1_p-RasGAP] + [Sum RasGAP];   {Sum RasGAP_p}
 
 Net Gab1/PIP3 binding [PIP3] + [Gab1] ↔ [PIP3-Gab1] + [Sum Gab1];   {Sum Gab1_p} , {Sum Gab1_p-Shc} , {Sum Gab1_p-RasGAP} , {Sum Gab1_p-PI-3K} , {SumGab1_p-PTP-1B}
 
 Net Akt Activation [Akt] ↔ [Aktstar];   {PIP3}
 
 Net PIP3 Production [PIP2] ↔ [PIP3];   {fint} , {E11_p} , {E12_p} , {E23_p} , {E24_p} , {E34_p} , {E44_p} , {ErbB1-ErbB3_p} , {ErbB1-ErbB3_p} , {Sum PI-3K}
 
 Net RasGTP Production [RasGDP] ↔ [RasGTP];   {Sum SOS} , {Sum RasGAP} , {Sum RasGAP_p}
 
 Net RasGAP Phosphorylation [Sum RasGAP] ↔ [Sum RasGAP_p];   {E11_p} , {E12_p} , {E23_p} , {E24_p} , {E34_p} , {E44_p} , {ErbB1-ErbB3_p} , {ErbB1-ErbB3_p} , {Sig-PTP-1B}
 
 Net Raf Activation [Raf] ↔ [Raf*];   {RasGTP}
 
 Net MEK Activation [MEK] ↔ [MEK*];   {Raf*}
 
 Net SOS S/T Phosphorylation [SOS] ↔ [SOS_p];   {ERK*}
 
 Net Gab1 S/T Phosphorylation [Gab1] ↔ [Gab1_p];   {ERK*}
 
 Grb2 binding to P3_A [Grb2] + [PIP3-Gab1] ↔ [Sum PIP3-Gab1-Grb2];  
 
 SOS binding to SigA-G [Sum PIP3-Gab1-Grb2] + [SOS] ↔ [Sum PIP3-Gab1-Grb2_SOS] + [Sum SOS];  
 
 Gab1 binding to SigG-O [Sum Grb2-SOS] + [Gab1] ↔ [Gab1_SumGrb2-SOS] + [Sum Gab1];   {Sum Gab1_p} , {Sum Gab1_p-Shc} , {Sum Gab1_p-RasGAP} , {Sum Gab1_p-PI-3K} , {SumGab1_p-PTP-1B}
 
 SOS binding to SigG-A [Sum Grb2-Gab1] + [SOS] ↔ [Gab1_SumGrb2-SOS] + [Sum SOS];  
 
 ErbB1/ErbB3 Heterodimerization [HRG-ErbB3] + [EGF-ErbB1] ↔ [ErbB1-ErbB3];  
 
 ErbB1/ErbB4 Heterodimerization [HRG-ErbB4] + [EGF-ErbB1] ↔ [ErbB1-ErbB4];  
 
 Net E13 Phosphorylation [ErbB1-ErbB3] ↔ [ErbB1-ErbB3_p];   {Sig-PTP-1B}
 
 Net E14 Phosphorylation [ErbB1-ErbB4] ↔ [ErbB1-ErbB3_p];   {Sig-PTP-1B}
 
 Net E13/Grb2 Binding [ErbB1-ErbB3_p] + [Grb2] ↔ [E13-Grb2] + [Sum Grb2];   {Sum Grb2-Gab1} , {Sum Grb2-SOS} , {Gab1_SumGrb2-SOS}
 
 Net E13/Shc Binding [ErbB1-ErbB3_p] + [Shc] ↔ [E13-Shc] + [Sum Shc];   {Sum Shc_p} , {Sum Shc_p-Grb2}
 
 Net E13/PI3K Binding [ErbB1-ErbB3_p] + [PI-3K] ↔ [E13-PI-3K] + [Sum PI-3K];  
 
 Net E13/RasGAP Binding [ErbB1-ErbB3_p] + [RasGAP] ↔ [E13-RasGAP] + [Sum RasGAP];   {Sum RasGAP_p}
 
 Net E14/Grb2 Binding [ErbB1-ErbB3_p] + [Grb2] ↔ [E14-Grb2] + [Sum Grb2];   {Sum Grb2-Gab1} , {Sum Grb2-SOS} , {Gab1_SumGrb2-SOS}
 
 Net E14/Shc Binding [ErbB1-ErbB3_p] + [Shc] ↔ [E14-Shc] + [Sum Shc];   {Sum Shc_p} , {Sum Shc_p-Grb2}
 
 Net E14/PI3K Binding [ErbB1-ErbB3_p] + [PI-3K] ↔ [E14-PI-3K] + [Sum PI-3K];  
 
 Net E14/RasGAP Binding [ErbB1-ErbB3_p] + [RasGAP] ↔ [E14-RasGAP] + [Sum RasGAP];   {Sum RasGAP_p}
 
 Net E11/PTP1B Binding [E11_p] + [PTP-1B] ↔ [E11-PTP-1B] + [Sig-PTP-1B];  
 
 Net E12/PTP1B Binding [E12_p] + [PTP-1B] ↔ [E12-PTP-1B] + [Sig-PTP-1B];  
 
 Net E23/PTP1B Binding [E23_p] + [PTP-1B] ↔ [E23-PTP-1B] + [Sig-PTP-1B];  
 
 Net E34/PTP1B Binding [E34_p] + [PTP-1B] ↔ [E34-PTP-1B] + [Sig-PTP-1B];  
 
 Net E24/PTP1B Binding [E24_p] + [PTP-1B] ↔ [E24-PTP-1B] + [Sig-PTP-1B];  
 
 Net E44/PTP1B Binding [E44_p] + [PTP-1B] ↔ [E44-PTP-1B] + [Sig-PTP-1B];  
 
 Net E13/PTP1B Binding [ErbB1-ErbB3_p] + [PTP-1B] ↔ [E13-PTP-1B] + [Sig-PTP-1B];  
 
 Net E14/PTP1B Binding [ErbB1-ErbB3_p] + [PTP-1B] ↔ [E14-PTP-1B] + [Sig-PTP-1B];  
 
 Net E1 S/T Phosphorylation [ErbB1] ↔ [E1_p-PTP-1B];   {ERK*}
 
 Net E2 S/T Phosphorylation [ErbB2] ↔ [E2_p-PTP-1B];   {ERK*}
 
 Net E4 S/T Phosphorylation [ErbB4] ↔ [E4_p-PTP-1B];   {ERK*}
 
 Net E_E1 S/T Phosphorylation [EGF-ErbB1] ↔ [E_E1_p-PTP-1B];   {ERK*}
 
 Net H_E4 S/T Phosphorylation [HRG-ErbB4] ↔ [H_E4_p-PTP-1B];   {ERK*}
 
 EGF binding to E1-PT [E1_p-PTP-1B] ↔ [E_E1_p-PTP-1B];   {EGF}
 
 HRG binding to E4-PT [E4_p-PTP-1B] ↔ [H_E4_p-PTP-1B];   {HRG}
 
 PTP1B binding to SigAP [Sum Gab1_p] + [PTP-1B] ↔ [SumGab1_p-PTP-1B] + [Sig-PTP-1B];  
 
 E11P Degradation [E11_p] → [Empty];  
 
 E11G Degradation [E11-Grb2] + [Sum Grb2] → [Grb2];  
 
 E11S Degradation [E11-Shc] + [Sum Shc] → [Shc];  
 
 E11R Degradation [E11-RasGAP] + [Sum RasGAP] → [RasGAP];  
 
 E11T Degradation [E11-PTP-1B] + [Sig-PTP-1B] → [PTP-1B];  
 
 1-1 Dimer Internalization Fraction [Empty] → [fint];  
 
 EGF in EC compartment [EGF] ↔ [Empty];   {ErbB1} , {EGF-ErbB1} , {E1_p-PTP-1B} , {E_E1_p-PTP-1B}
 
 HRG in EC compartment [HRG] ↔ [Empty];   {E4_p-PTP-1B} , {H_E4_p-PTP-1B} , {ErbB3} , {HRG-ErbB3} , {ErbB4} , {HRG-ErbB4}
 
 ERK binding to MEKstar [ERK] + [MEK*] ↔ [ERK-MEK*];  
 
 pERK production [ERK-MEK*] → [p_ERK] + [MEK*];  
 
 ERK binding to MEKstar [p_ERK] + [MEK*] ↔ [p_ERK-MEK*];  
 
 ERKstar production [p_ERK-MEK*] → [ERK*] + [MEK*];  
 
 ERKstar binding to Phosphatase [ERK*] + [ERKpase] ↔ [ERK*-ERKpase];  
 
 ERKstar dephosphorylation [ERK*-ERKpase] → [p_ERK] + [ERKpase];  
 
 pERK binding to Phosphatase [p_ERK] + [ERKpase] ↔ [p_ERK-ERKpase];  
 
 pERK dephosphorylation [p_ERK-ERKpase] → [ERK] + [ERKpase];  
 
Rules (2)
 
 Assignment Rule (name: norm_Akt_star) normalized Akt* = Aktstar/18.8
 
 Assignment Rule (name: norm_Erk_star) normalized Erk* = (ERKstar+ERKstar_ERKpase)/589.5
 
 membrane Spatial dimensions: 2.0  Compartment size: 1.0
 
 ErbB1
Compartment: membrane
Initial amount: 274.0
 
 ErbB2
Compartment: membrane
Initial amount: 158.0
 
 ErbB3
Compartment: membrane
Initial amount: 294.0
 
 ErbB4
Compartment: membrane
Initial amount: 399.0
 
 EGF-ErbB1
Compartment: membrane
Initial amount: 0.0
 
 HRG-ErbB3
Compartment: membrane
Initial amount: 0.0
 
 HRG-ErbB4
Compartment: membrane
Initial amount: 0.0
 
 (EGF-ErbB1)2
Compartment: membrane
Initial amount: 0.0
 
 EGF-ErbB1-ErbB2
Compartment: membrane
Initial amount: 0.0
 
 HRG-ErbB3-ErbB2
Compartment: membrane
Initial amount: 0.0
 
 (HRG-ErbB3/4)2
Compartment: membrane
Initial amount: 0.0
 
 HRG-Erb4-ErbB2
Compartment: membrane
Initial amount: 0.0
 
 (HRG-Erb4)2
Compartment: membrane
Initial amount: 0.0
 
 E11_p
Compartment: membrane
Initial amount: 0.0
 
 E12_p
Compartment: membrane
Initial amount: 0.0
 
   E23_p
Compartment: membrane
Initial amount: 0.0
 
   E34_p
Compartment: membrane
Initial amount: 0.0
 
   E24_p
Compartment: membrane
Initial amount: 0.0
 
   E44_p
Compartment: membrane
Initial amount: 0.0
 
 Grb2
Compartment: membrane
Initial amount: 82.4
 
 Shc
Compartment: membrane
Initial amount: 11.5
 
 PI-3K
Compartment: membrane
Initial amount: 46.4
 
 RasGAP
Compartment: membrane
Initial amount: 93.6
 
 SOS
Compartment: membrane
Initial amount: 82.3
 
 Gab1
Compartment: membrane
Initial amount: 43.1
 
   E11-Grb2
Compartment: membrane
Initial amount: 0.0
 
   E11-Shc
Compartment: membrane
Initial amount: 0.0
 
   E11-RasGAP
Compartment: membrane
Initial amount: 0.0
 
   E12-Grb2
Compartment: membrane
Initial amount: 0.0
 
   E12-Shc
Compartment: membrane
Initial amount: 0.0
 
   E12-RasGAP
Compartment: membrane
Initial amount: 0.0
 
   E23-Grb2
Compartment: membrane
Initial amount: 0.0
 
   E23-Shc
Compartment: membrane
Initial amount: 0.0
 
   E23-PI-3K
Compartment: membrane
Initial amount: 0.0
 
   E23-RasGAP
Compartment: membrane
Initial amount: 0.0
 
   E34-Grb2
Compartment: membrane
Initial amount: 0.0
 
   E34-Shc
Compartment: membrane
Initial amount: 0.0
 
   E34-PI-3K
Compartment: membrane
Initial amount: 0.0
 
   E34-RasGAP
Compartment: membrane
Initial amount: 0.0
 
   E24-Grb2
Compartment: membrane
Initial amount: 0.0
 
   E24-Shc
Compartment: membrane
Initial amount: 0.0
 
   E24-PI-3K
Compartment: membrane
Initial amount: 0.0
 
   E24-RasGAP
Compartment: membrane
Initial amount: 0.0
 
   E44-Grb2
Compartment: membrane
Initial amount: 0.0
 
   E44-Shc
Compartment: membrane
Initial amount: 0.0
 
   E44-PI-3K
Compartment: membrane
Initial amount: 0.0
 
   E44-RasGAP
Compartment: membrane
Initial amount: 0.0
 
   Sum Grb2
Compartment: membrane
Initial amount: 0.0
 
   Sum Shc
Compartment: membrane
Initial amount: 0.0
 
   Sum PI-3K
Compartment: membrane
Initial amount: 0.0
 
   Sum RasGAP
Compartment: membrane
Initial amount: 0.0
 
   Sum Gab1
Compartment: membrane
Initial amount: 0.0
 
   Sum Shc_p
Compartment: membrane
Initial amount: 0.0
 
   Sum Gab1_p
Compartment: membrane
Initial amount: 0.0
 
   Sum Grb2-SOS
Compartment: membrane
Initial amount: 0.0
 
   Sum Grb2-Gab1
Compartment: membrane
Initial amount: 0.0
 
   Sum Shc_p-Grb2
Compartment: membrane
Initial amount: 0.0
 
   Sum Gab1_p-Shc
Compartment: membrane
Initial amount: 0.0
 
   Sum Gab1_p-PI-3K
Compartment: membrane
Initial amount: 0.0
 
   Sum Gab1_p-RasGAP
Compartment: membrane
Initial amount: 0.0
 
   Empty
Compartment: membrane
Initial amount: 0.0
 
   PIP3-Gab1
Compartment: membrane
Initial amount: 0.0
 
 PIP2
Compartment: membrane
Initial amount: 197.0
 
 PIP3
Compartment: membrane
Initial amount: 0.0
 
 Akt
Compartment: membrane
Initial amount: 444.0
 
 RasGDP
Compartment: membrane
Initial amount: 95.7
 
 RasGTP
Compartment: membrane
Initial amount: 0.0
 
   Sum RasGAP_p
Compartment: membrane
Initial amount: 0.0
 
   Raf
Compartment: membrane
Initial amount: 743.0
 
 Raf*
Compartment: membrane
Initial amount: 0.0
 
 MEK
Compartment: membrane
Initial amount: 772.0
 
 MEK*
Compartment: membrane
Initial amount: 0.0
 
 ERK
Compartment: membrane
Initial amount: 750.0
 
   ERK*
Compartment: membrane
Initial amount: 0.0
 
   SOS_p
Compartment: membrane
Initial amount: 0.0
 
   Gab1_p
Compartment: membrane
Initial amount: 0.0
 
   Gab1_SumGrb2-SOS
Compartment: membrane
Initial amount: 0.0
 
   Sum PIP3-Gab1-Grb2
Compartment: membrane
Initial amount: 0.0
 
   Sum PIP3-Gab1-Grb2_SOS
Compartment: membrane
Initial amount: 0.0
 
   Sum SOS
Compartment: membrane
Initial amount: 0.0
 
   ErbB1-ErbB3
Compartment: membrane
Initial amount: 0.0
 
   ErbB1-ErbB4
Compartment: membrane
Initial amount: 0.0
 
   ErbB1-ErbB3_p
Compartment: membrane
Initial amount: 0.0
 
   ErbB1-ErbB3_p
Compartment: membrane
Initial amount: 0.0
 
   E13-Grb2
Compartment: membrane
Initial amount: 0.0
 
   E13-Shc
Compartment: membrane
Initial amount: 0.0
 
   E13-PI-3K
Compartment: membrane
Initial amount: 0.0
 
   E13-RasGAP
Compartment: membrane
Initial amount: 0.0
 
   E14-Grb2
Compartment: membrane
Initial amount: 0.0
 
   E14-Shc
Compartment: membrane
Initial amount: 0.0
 
   E14-PI-3K
Compartment: membrane
Initial amount: 0.0
 
   E14-RasGAP
Compartment: membrane
Initial amount: 0.0
 
 PTP-1B
Compartment: membrane
Initial amount: 500.0
 
   E11-PTP-1B
Compartment: membrane
Initial amount: 0.0
 
   E12-PTP-1B
Compartment: membrane
Initial amount: 0.0
 
   E23-PTP-1B
Compartment: membrane
Initial amount: 0.0
 
   E34-PTP-1B
Compartment: membrane
Initial amount: 0.0
 
   E24-PTP-1B
Compartment: membrane
Initial amount: 0.0
 
   E44-PTP-1B
Compartment: membrane
Initial amount: 0.0
 
   E13-PTP-1B
Compartment: membrane
Initial amount: 0.0
 
   E14-PTP-1B
Compartment: membrane
Initial amount: 0.0
 
   Sig-PTP-1B
Compartment: membrane
Initial amount: 0.0
 
   E1_p-PTP-1B
Compartment: membrane
Initial amount: 0.0
 
   E2_p-PTP-1B
Compartment: membrane
Initial amount: 0.0
 
   E4_p-PTP-1B
Compartment: membrane
Initial amount: 0.0
 
   E_E1_p-PTP-1B
Compartment: membrane
Initial amount: 0.0
 
   H_E4_p-PTP-1B
Compartment: membrane
Initial amount: 0.0
 
   Aktstar
Compartment: membrane
Initial amount: 0.0
 
   SumGab1_p-PTP-1B
Compartment: membrane
Initial amount: 0.0
 
 EGF
Compartment: membrane
Initial amount: 10.0
 
 HRG
Compartment: membrane
Initial amount: 10.0
 
   fint
Compartment: membrane
Initial amount: 0.0
 
   p_ERK
Compartment: membrane
Initial amount: 0.0
 
   ERK-MEK*
Compartment: membrane
Initial amount: 0.0
 
   p_ERK-MEK*
Compartment: membrane
Initial amount: 0.0
 
   p_ERK-ERKpase
Compartment: membrane
Initial amount: 0.0
 
 ERKpase
Compartment: membrane
Initial amount: 0.0
 
   ERK*-ERKpase
Compartment: membrane
Initial amount: 35.0
 
   normalized Akt*
Compartment: membrane
 
   normalized Erk*
Compartment: membrane
 
Global Parameters (240)
 
   ErbB1_Abund
Value: 274.0
Constant
 
   ErbB2_Abund
Value: 158.0
Constant
 
   ErbB3_Abund
Value: 294.0
Constant
 
   ErbB4_Abund
Value: 399.0
Constant
 
   Grb2_Abund
Value: 82.4
Constant
 
   Shc_Abund
Value: 11.5
Constant
 
   PI3K_Abund
Value: 46.4
Constant
 
   RasGAP_Abund
Value: 93.6
Constant
 
   SOS_Abund
Value: 82.3
Constant
 
   Gab1_Abund
Value: 43.1
Constant
 
   PIP2_Abund
Value: 197.0
Constant
 
   Akt_Abund
Value: 444.2921
Constant
 
   Ras_Abund
Value: 95.7
Constant
 
   Raf_Abund
Value: 743.0
Constant
 
   MEK_Abund
Value: 772.0
Constant
 
   ERK_Abund
Value: 749.9716
Constant
 
   VmaxPY
Value: 223.8776
Constant
 
   KmPY
Value: 486.1398
Constant
 
   kdeg
Value: 0.0259
Constant
 
   kf47
Value: 24.6048
Constant
 
   Vmaxr47
Value: 590.5058
Constant
 
   Kmf47
Value: 698.6022
Constant
 
   Kmr47
Value: 483.8622
Constant
 
   kf48
Value: 16.833
Constant
 
   Kmf48
Value: 715.5688
Constant
 
   Kmr48
Value: 324.9294
Constant
 
   PTEN
Value: 693.5786
Constant
 
   kf49
Value: 44.3501
Constant
 
   kr49
Value: 552.6746
Constant
 
   Kmf49
Value: 343.2483
Constant
 
   Kmr49
Value: 753.1667
Constant
 
   Kmr49b
Value: 381.2208
Constant
 
   kr49b
Value: 640.8212
Constant
 
   kf51
Value: 3.6515
Constant
 
   kr51
Constant
 
   Vmaxr51
Value: 16.737
Constant
 
   Kmf51
Value: 599.7076
Constant
 
   Kmr51
Value: 346.4779
Constant
 
   Kmrb51
Value: 988.4496
Constant
 
   kf52
Value: 0.7745
Constant
 
   Vmaxr52
Value: 199.2773
Constant
 
   Kmf52
Value: 545.4408
Constant
 
   Kmr52
Value: 675.2994
Constant
 
   kf53
Value: 0.6094
Constant
 
   Vmaxr53
Value: 59.2314
Constant
 
   Kmf53
Value: 812.254
Constant
 
   Kmr53
Value: 944.7692
Constant
 
   kf54
Value: 0.0538
Constant
 
   Vmaxr54
Value: 588.2671
Constant
 
   Kmf54
Value: 457.9645
Constant
 
   Kmr54
Value: 336.183
Constant
 
   kf55
Value: 0.2256
Constant
 
   Vmaxr55
Value: 646.9003
Constant
 
   Kmf55
Value: 460.9446
Constant
 
   Kmr55
Value: 643.9247
Constant
 
   kf38
Value: 279.9929
Constant
 
   kf39
Value: 385.7428
Constant
 
   kf50
Value: 389.1061
Constant
 
   a98
Value: 0.0849
Constant
 
   b98
Value: 0.1833
Constant
 
   koff46
Value: 0.5194
Constant
 
   EGF_off
Value: 0.0175
Constant
 
   HRGoff_3
Value: 9.0E-4
Constant
 
   HRGoff_4
Value: 0.0973
Constant
 
   koff4
Value: 0.1717
Constant
 
   koff5
Value: 4.3985
Constant
 
   koff6
Value: 2.6619
Constant
 
   koff7
Value: 8.0557
Constant
 
   koff8
Value: 9.1034
Constant
 
   koff9
Value: 5.5425
Constant
 
   koff57
Value: 0.4526
Constant
 
   koff16
Value: 0.5737
Constant
 
   koff17
Value: 4.6874
Constant
 
   koff18
Value: 2.2768
Constant
 
   koff19
Value: 2.3361
Constant
 
   koff20
Value: 0.6761
Constant
 
   koff21
Value: 4.7291
Constant
 
   koff22
Value: 3.6962
Constant
 
   koff23
Value: 2.3619
Constant
 
   koff24
Value: 4.4226
Constant
 
   koff25
Value: 2.225
Constant
 
   koff26
Value: 0.0103
Constant
 
   koff27
Value: 1.8922
Constant
 
   koff28
Value: 4.6432
Constant
 
   koff29
Value: 2.0148
Constant
 
   koff30
Value: 4.9936
Constant
 
   koff31
Value: 1.2204
Constant
 
   koff32
Value: 3.8752
Constant
 
   koff33
Value: 1.2817
Constant
 
   koff34
Value: 3.2036
Constant
 
   koff35
Value: 1.8696
Constant
 
   koff36
Value: 1.2567
Constant
 
   koff37
Value: 0.4059
Constant
 
   koff65
Value: 0.1185
Constant
 
   koff66
Value: 2.2988
Constant
 
   koff67
Value: 1.6142
Constant
 
   koff40
Value: 3.1051
Constant
 
   koff41
Value: 7.0487
Constant
 
   koff42
Value: 3.5195
Constant
 
   koff43
Value: 0.5441
Constant
 
   koff44
Value: 0.4265
Constant
 
   koff45
Value: 3.9967
Constant
 
   koff58
Value: 6.3059
Constant
 
   koff59
Value: 9.172
Constant
 
   koff68
Value: 2.8871
Constant
 
   PTP1B_Abund
Value: 500.0
Constant
 
   kPTP10
Value: 29.8531
Constant
 
   kPTP11
Value: 78.204
Constant
 
   kPTP12
Value: 11.4211
Constant
 
   kPTP13
Value: 55.2104
Constant
 
   kPTP14
Value: 57.7506
Constant
 
   kPTP15
Value: 60.2628
Constant
 
   kPTP63
Value: 7.4766
Constant
 
   kPTP64
Value: 48.6335
Constant
 
   koff73
Value: 3.0048
Constant
 
   koff74
Value: 1.2496
Constant
 
   koff75
Value: 1.4323
Constant
 
   koff76
Value: 2.1542
Constant
 
   koff77
Value: 1.2237
Constant
 
   koff78
Value: 0.2007
Constant
 
   koff79
Value: 1.1852
Constant
 
   koff80
Value: 2.9373
Constant
 
   kPTP38
Value: 83.4465
Constant
 
   kPTP39
Value: 79.6132
Constant
 
   koff88
Value: 3.9255
Constant
 
   kPTP50
Value: 96.5716
Constant
 
   kf81
Value: 1.361
Constant
 
   Vmaxr81
Value: 242.6034
Constant
 
   Kmf81
Value: 485.2626
Constant
 
   Kmr81
Value: 323.4012
Constant
 
   kf82
Value: 6.9987
Constant
 
   Vmaxr82
Value: 398.1931
Constant
 
   Kmf82
Value: 781.4374
Constant
 
   Kmr82
Value: 595.8395
Constant
 
   kf83
Value: 1.7628
Constant
 
   Vmaxr83
Value: 534.0531
Constant
 
   Kmf83
Value: 609.4766
Constant
 
   Kmr83
Value: 653.5184
Constant
 
   kf84
Value: 4.6894
Constant
 
   Vmaxr84
Value: 634.1626
Constant
 
   Kmf84
Value: 622.3847
Constant
 
   Kmr84
Value: 258.4637
Constant
 
   kf85
Value: 6.7591
Constant
 
   Vmaxr85
Value: 369.2261
Constant
 
   Kmf85
Value: 179.6486
Constant
 
   Kmr85
Value: 290.7667
Constant
 
   kcon49
Value: 9.9783
Constant
 
   kon1
Value: 1.0086E-4
Constant
 
   kon86
Value: 0.0038
Constant
 
   kon2
Value: 0.0059
Constant
 
   kon3
Value: 0.0334
Constant
 
   kon87
Value: 8.0E-4
Constant
 
   kon4
Value: 0.5005
Constant
 
   kon5
Value: 2.5427
Constant
 
   kon6
Value: 0.2283
Constant
 
   kon7
Value: 1.0606
Constant
 
   kon8
Value: 1.0259
Constant
 
   kon9
Value: 2.2868
Constant
 
   kon57
Value: 0.0039
Constant
 
   kf10
Value: 0.6496
Constant
 
   kf11
Value: 0.3721
Constant
 
   kf12
Value: 1.8012
Constant
 
   kf13
Value: 0.8875
Constant
 
   kf14
Value: 6.1726
Constant
 
   kf15
Value: 1.3565
Constant
 
   kf63
Value: 0.9297
Constant
 
   kf64
Value: 1.2083
Constant
 
   kon16
Value: 0.0097
Constant
 
   kon17
Value: 0.0049
Constant
 
   kon18
Value: 0.0117
Constant
 
   kon73
Value: 0.0116
Constant
 
   kon19
Value: 0.0896
Constant
 
   kon20
Value: 0.0478
Constant
 
   kon21
Value: 0.0114
Constant
 
   kon74
Value: 0.0133
Constant
 
   kon22
Value: 7.0E-4
Constant
 
   kon23
Value: 0.0138
Constant
 
   kon24
Value: 0.0050
Constant
 
   kon25
Value: 0.0995
Constant
 
   kon75
Value: 0.0137
Constant
 
   kon26
Value: 0.0355
Constant
 
   kon27
Value: 0.0201
Constant
 
   kon28
Value: 0.0074
Constant
 
   kon29
Value: 0.0346
Constant
 
   kon76
Value: 0.0053
Constant
 
   kon30
Value: 0.0020
Constant
 
   kon31
Value: 0.0032
Constant
 
   kon32
Value: 9.0E-4
Constant
 
   kon33
Value: 0.0335
Constant
 
   kon77
Value: 0.0101
Constant
 
   kon34
Value: 1.0E-4
Constant
 
   kon35
Value: 0.0602
Constant
 
   kon36
Value: 0.0043
Constant
 
   kon37
Value: 0.0791
Constant
 
   kon78
Value: 0.0076
Constant
 
   kon79
Value: 0.0078
Constant
 
   kon65
Value: 0.0123
Constant
 
   kon66
Value: 1.9264E-4
Constant
 
   kon67
Value: 6.6667E-5
Constant
 
   kon80
Value: 2.0E-4
Constant
 
   kon40
Value: 0.0191
Constant
 
   kon41
Value: 0.0051
Constant
 
   kon42
Value: 0.0023
Constant
 
   kon43
Value: 0.0127
Constant
 
   kon44
Value: 0.0122
Constant
 
   kon45
Value: 0.0028
Constant
 
   kon88
Value: 0.0108
Constant
 
   kon46
Value: 0.0148
Constant
 
   kon58
Value: 0.0215
Constant
 
   kon59
Value: 0.0077
Constant
 
   kon60
Value: 1.1994E-4
Constant
 
   VeVc
Value: 33.3
Constant
 
   koff60
Value: 4.9981
Constant
 
   koff61
Value: 5.229
Constant
 
   kon61
Value: 0.8048
Constant
 
   kon62
Value: 1.782
Constant
 
   koff62
Value: 5.5142
Constant
 
   kon68
Value: 0.0045
Constant
 
   kon69
Value: 0.0084
Constant
 
   koff69
Value: 3.97
Constant
 
   kon70
Value: 0.0116
Constant
 
   koff70
Value: 2.6069
Constant
 
   kon71
Value: 0.0078
Constant
 
   koff71
Value: 2.2988
Constant
 
   kon72
Value: 0.0355
Constant
 
   koff72
Value: 0.907
Constant
 
   eps
Value: 1.0E-16
Constant
 
   kon89
Value: 0.1997
Constant
 
   koff89
Value: 99.9637
Constant
 
   kcat90
Value: 20.0037
Constant
 
   kon91
Value: 0.1966
Constant
 
   koff91
Value: 99.9983
Constant
 
   kcat92
Value: 0.2004
Constant
 
   kon93
Value: 0.2003
Constant
 
   koff93
Value: 100.0037
Constant
 
   kcat94
Value: 0.9966
Constant
 
   kon95
Value: 0.1993
Constant
 
   koff95
Value: 100.0023
Constant
 
   kcat96
Value: 19.9851
Constant
 
   ERKPpase_Abund
Value: 35.005
Constant
 
Representative curation result(s)
Representative curation result(s) of BIOMD0000000175

Curator's comment: (updated: 18 Jul 2008 14:35:48 BST)

reproduction of figure 4 using SBMLodeSolver (20080507)

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