Birtwistle2007_ErbB_Signalling
Model Identifier
BIOMD0000000175
Short description
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.
Format
SBML
(L2V3)
Related Publication
-
Ligand-dependent responses of the ErbB signaling network: experimental and modeling analyses.
- Birtwistle MR, Hatakeyama M, Yumoto N, Ogunnaike BA, Hoek JB, Kholodenko BN
- Molecular Systems Biology , 0/ 2007 , Volume 3 , pages: 144 , PubMed ID: 18004277
- Department of Chemical Engineering, University of Delaware, Newark, DE, USA.
- Deregulation of ErbB signaling plays a key role in the progression of multiple human cancers. To help understand ErbB signaling quantitatively, in this work we combine traditional experiments with computational modeling, building a model that describes how stimulation of all four ErbB receptors with epidermal growth factor (EGF) and heregulin (HRG) leads to activation of two critical downstream proteins, extracellular-signal-regulated kinase (ERK) and Akt. Model analysis and experimental validation show that (i) ErbB2 overexpression, which occurs in approximately 25% of all breast cancers, transforms transient EGF-induced signaling into sustained signaling, (ii) HRG-induced ERK activity is much more robust to the ERK cascade inhibitor U0126 than EGF-induced ERK activity, and (iii) phosphoinositol-3 kinase is a major regulator of post-peak but not pre-peak EGF-induced ERK activity. Sensitivity analysis leads to the hypothesis that ERK activation is robust to parameter perturbation at high ligand doses, while Akt activation is not.
Contributors
Submitter of the first revision: Molecular Systems Biology
Submitter of this revision: Molecular Systems Biology
Modellers: Molecular Systems Biology
Submitter of this revision: Molecular Systems Biology
Modellers: Molecular Systems Biology
Metadata information
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isDescribedBy
hasTaxon
hasVersion
isVersionOf
Curation status
Curated
Tags
Connected external resources
SBGN view in Newt Editor
| Name | Description | Size | Actions |
|---|---|---|---|
Model files |
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| BIOMD0000000175_url.xml | SBML L2V3 representation of Birtwistle2007_ErbB_Signalling | 222.10 KB | Preview | Download |
Additional files |
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| BIOMD0000000175-biopax2.owl | Auto-generated BioPAX (Level 2) | 190.20 KB | Preview | Download |
| BIOMD0000000175-biopax3.owl | Auto-generated BioPAX (Level 3) | 335.09 KB | Preview | Download |
| BIOMD0000000175.m | Auto-generated Octave file | 66.76 KB | Preview | Download |
| BIOMD0000000175.pdf | Auto-generated PDF file | 784.48 KB | Preview | Download |
| BIOMD0000000175.png | Auto-generated Reaction graph (PNG) | 4.13 MB | Preview | Download |
| BIOMD0000000175.sci | Auto-generated Scilab file | 58.85 KB | Preview | Download |
| BIOMD0000000175.svg | Auto-generated Reaction graph (SVG) | 374.34 KB | Preview | Download |
| BIOMD0000000175.vcml | Auto-generated VCML file | 916.00 Bytes | Preview | Download |
| BIOMD0000000175.xpp | Auto-generated XPP file | 50.36 KB | Preview | Download |
| BIOMD0000000175_urn.xml | Auto-generated SBML file with URNs | 219.79 KB | Preview | Download |
- Model originally submitted by : Molecular Systems Biology
- Submitted: Jul 18, 2008 2:45:02 PM
- Last Modified: Apr 8, 2016 4:42:16 PM
Revisions
-
Version: 2
- Submitted on: Apr 8, 2016 4:42:16 PM
- Submitted by: Molecular Systems Biology
- With comment: Current version of Birtwistle2007_ErbB_Signalling
-
Version: 1
- Submitted on: Jul 18, 2008 2:45:02 PM
- Submitted by: Molecular Systems Biology
- With comment: Original import of ErbB
(*) You might be seeing discontinuous
revisions as only public revisions are displayed here. Any private revisions
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Legends
: Variable used inside SBML models
: Variable used inside SBML models
Species
| Species | Initial Concentration/Amount |
|---|---|
| E34P | 0.0 nmol |
| E44P | 0.0 nmol |
| G Growth factor receptor-bound protein 2 ; 108355 |
82.4 nmol |
| A GRB2-associated-binding protein 1 ; 604439 |
43.1 nmol |
| E24S | 0.0 nmol |
| T 176885 ; Tyrosine-protein phosphatase non-receptor type 1 |
500.0 nmol |
| E24T | 0.0 nmol |
| SigT | 0.0 nmol |
| E1 PT | 0.0 nmol |
| ERKpase 602747 ; 600714 ; 602748 ; Dual specificity protein phosphatase 1 ; Dual specificity protein phosphatase 4 ; Dual specificity protein phosphatase 6 |
0.0 nmol |
| H E4 Pro-neuregulin-1, membrane-bound isoform ; Receptor tyrosine-protein kinase erbB-4 |
0.0 nmol |
| I Phosphoinositide 3-kinase regulatory subunit 5 ; Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform |
46.4 nmol |
Reactions
| Reactions | Rate | Parameters |
|---|---|---|
| E34P + S => E34S + SigS; SigSP, SigSP_G | membrane*(3*kon27*E34P*S-koff27*SigS/(SigS+SigSP+SigSP_G+eps)*E34S) | koff27 = 1.8922; eps = 1.0E-16; kon27 = 0.0201 |
| E44P + G => E44G + SigG; SigG_A, SigG_O, A_SigG_O | membrane*(4*kon34*E44P*G-koff34*SigG/(SigG+SigG_A+SigG_O+A_SigG_O+eps)*E44G) | koff34 = 3.2036; eps = 1.0E-16; kon34 = 1.0E-4 |
| E23P + G => E23G + SigG; SigG_A, SigG_O, A_SigG_O | membrane*(3*kon22*E23P*G-koff22*SigG/(SigG+SigG_A+SigG_O+A_SigG_O+eps)*E23G) | eps = 1.0E-16; koff22 = 3.6962; kon22 = 7.0E-4 |
| SigG_O + A => A_SigG_O + SigA; SigAP, SigAP_S, SigAP_R, SigAP_I, SigAP_T | membrane*(kon59*SigG_O*A-koff59*A_SigG_O*SigA/(eps+SigA+SigAP+SigAP_S+SigAP_R+SigAP_I+SigAP_T)) | eps = 1.0E-16; kon59 = 0.0077; koff59 = 9.172 |
| E24P + S => E24S + SigS; SigSP, SigSP_G | membrane*(4*kon31*E24P*S-koff31*SigS/(SigS+SigSP+SigSP_G+eps)*E24S) | kon31 = 0.0032; koff31 = 1.2204; eps = 1.0E-16 |
| E12P + T => E12T + SigT | membrane*(3*kon74*E12P*T-koff74*E12T) | kon74 = 0.0133; koff74 = 1.2496 |
| E24P + T => E24T + SigT | membrane*(2*kon77*E24P*T-koff77*E24T) | koff77 = 1.2237; kon77 = 0.0101 |
| E11P + T => E11T + SigT | membrane*(4*kon73*E11P*T-koff73*E11T) | kon73 = 0.0116; koff73 = 3.0048 |
| E1 => E1_PT; ERKstar | membrane*(kf81*E1*ERKstar/(Kmf81+E1)-Vmaxr81*E1_PT/(Kmr81+E1_PT)) | Kmf81 = 485.2626; Kmr81 = 323.4012; Vmaxr81 = 242.6034; kf81 = 1.361 |
| ERKstar + ERKpase => ERKstar_ERKpase | membrane*(kon93*ERKstar*ERKpase-koff93*ERKstar_ERKpase) | kon93 = 0.2003; koff93 = 100.0037 |
| pERK_ERKpase => ERK + ERKpase | membrane*kcat96*pERK_ERKpase | kcat96 = 19.9851 |
| H_E4 + E_E1 => E14 | membrane*(kon62*H_E4*E_E1-koff62*E14) | koff62 = 5.5142; kon62 = 1.782 |
| E11G + SigG => G | membrane*kdeg*E11G | kdeg = 0.0259 |
| E34P + I => E34I + SigI | membrane*(4*kon28*E34P*I-koff28*E34I) | koff28 = 4.6432; kon28 = 0.0074 |
Curator's comment:
(added: 18 Jul 2008, 14:35:48, updated: 18 Jul 2008, 14:35:48)
(added: 18 Jul 2008, 14:35:48, updated: 18 Jul 2008, 14:35:48)
reproduction of figure 4 using SBMLodeSolver (20080507)