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  • Ligand-dependent responses of the ErbB signaling network: experimental and modeling analyses. Click here to expand
  • Marc R Birtwistle, Mariko Hatakeyama, Noriko Yumoto, Babatunde A Ogunnaike, Jan B Hoek, Boris N Kholodenko
  • 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.
Submitter of the first revision: Molecular Systems Biology
Submitter of this revision: Molecular Systems Biology
Modeller: Molecular Systems Biology

Metadata information

is (2 statements)
BioModels Database BIOMD0000000175
BioModels Database MODEL5563731079

isDescribedBy (1 statement)
PubMed 18004277

hasTaxon (1 statement)
Taxonomy Homo sapiens

hasVersion (2 statements)
Gene Ontology MAPK cascade
Reactome Signalling to ERKs

isVersionOf (1 statement)
Gene Ontology ERBB signaling pathway

Curation status

Connected external resources

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
  • 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

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Curator's comment:
(added: 18 Jul 2008, 14:35:48, updated: 18 Jul 2008, 14:35:48)
reproduction of figure 4 using SBMLodeSolver (20080507)