Birtwistle2007_ErbB_Signalling

  public model
Model Identifier
BIOMD0000000175
Short description
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

Metadata information

is
BioModels Database MODEL5563731079
BioModels Database BIOMD0000000175
isDescribedBy
PubMed 18004277
hasTaxon
Taxonomy Homo sapiens
hasVersion
Gene Ontology MAPK cascade
Reactome Signalling to ERKs
isVersionOf
Gene Ontology ERBB signaling pathway

Curation status
Curated

Tags

Connected external resources

SBGN view in Newt Editor

Name Description Size Actions

Model files

BIOMD0000000175_url.xml SBML L2V3 representation of Birtwistle2007_ErbB_Signalling 222.10 KB Preview | Download

Additional files

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 public model Download this version
    • Submitted on: Apr 8, 2016 4:42:16 PM
    • Submitted by: Molecular Systems Biology
    • With comment: Current version of Birtwistle2007_ErbB_Signalling
  • Version: 1 public model Download this version
    • 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 unpublished model revision of this model will only be shown to the submitter and their collaborators.

Legends
: Variable used inside SBML models


Species
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)
reproduction of figure 4 using SBMLodeSolver (20080507)