Hornberg2005 - MAPKsignalling

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Short description
Hornberg2005 - MAPKsignalling
Large model of the ERK signalling network. Results from this model were used to generate a simplified version of the network.

This model is described in the article:

Hornberg JJ, Binder B, Bruggeman FJ, Schoeberl B, Heinrich R, Westerhoff HV.
Oncogene 2005 Aug; 24(36): 5533-5542

Abstract:

Oncogenesis results from changes in kinetics or in abundance of proteins in signal transduction networks. Recently, it was shown that control of signalling cannot reside in a single gene product, and might well be dispersed over many components. Which of the reactions in these complex networks are most important, and how can the existing molecular information be used to understand why particular genes are oncogenes whereas others are not? We implement a new method to help address such questions. We apply control analysis to a detailed kinetic model of the epidermal growth factor-induced mitogen-activated protein kinase network. We determine the control of each reaction with respect to three biologically relevant characteristics of the output of this network: the amplitude, duration and integrated output of the transient phosphorylation of extracellular signal-regulated kinase (ERK). We confirm that control is distributed, but far from randomly: a small proportion of reactions substantially control signalling. In particular, the activity of Raf is in control of all characteristics of the transient profile of ERK phosphorylation, which may clarify why Raf is an oncogene. Most reactions that really matter for one signalling characteristic are also important for the other characteristics. Our analysis also predicts the effects of mutations and changes in gene expression.

This model is hosted on BioModels Database and identified by: BIOMD0000000667.

To cite BioModels Database, please use: Chelliah V et al. BioModels: ten-year anniversary. Nucl. Acids Res. 2015, 43(Database issue):D542-8.

To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

Format
SBML (L2V4)
Related Publication
  • Control of MAPK signalling: from complexity to what really matters.
  • Hornberg JJ, Binder B, Bruggeman FJ, Schoeberl B, Heinrich R, Westerhoff HV
  • Oncogene , 8/ 2005 , Volume 24 , Issue 36 , pages: 5533-5542
  • Department of Molecular Cell Physiology, Institute of Molecular Cell Biology, Faculty of Earth and Life Sciences, Vrije Universiteit, Amsterdam, The Netherlands.
  • Oncogenesis results from changes in kinetics or in abundance of proteins in signal transduction networks. Recently, it was shown that control of signalling cannot reside in a single gene product, and might well be dispersed over many components. Which of the reactions in these complex networks are most important, and how can the existing molecular information be used to understand why particular genes are oncogenes whereas others are not? We implement a new method to help address such questions. We apply control analysis to a detailed kinetic model of the epidermal growth factor-induced mitogen-activated protein kinase network. We determine the control of each reaction with respect to three biologically relevant characteristics of the output of this network: the amplitude, duration and integrated output of the transient phosphorylation of extracellular signal-regulated kinase (ERK). We confirm that control is distributed, but far from randomly: a small proportion of reactions substantially control signalling. In particular, the activity of Raf is in control of all characteristics of the transient profile of ERK phosphorylation, which may clarify why Raf is an oncogene. Most reactions that really matter for one signalling characteristic are also important for the other characteristics. Our analysis also predicts the effects of mutations and changes in gene expression.
Contributors
Vijayalakshmi Chelliah, administrator

Metadata information

is
BioModels Database MODEL0848279215
BIOMD0000000667
isDescribedBy
PubMed 16007170
PubMed 16007170
isVersionOf
Curation status
Curated
Name Description Size Actions

Model files

BIOMD0000000667_url.xml SBML L2V4 representation of Hornberg2005 - MAPKsignalling 573.99 KB Preview | Download

Additional files

BIOMD0000000667.m Auto-generated Octave file 48.06 KB Preview | Download
BIOMD0000000667.png Auto-generated Reaction graph (PNG) 2.09 MB Preview | Download
BIOMD0000000667-biopax2.owl Auto-generated BioPAX (Level 2) 232.25 KB Preview | Download
MODEL0848279215.cps COPASI file with annotations and plot to produce figure 2 that shows ERK-PP concentration over time (seconds) 600.71 KB Preview | Download
BIOMD0000000667.xpp Auto-generated XPP file 38.51 KB Preview | Download
BIOMD0000000667.pdf Auto-generated PDF file 545.95 KB Preview | Download
BIOMD0000000667_urn.xml Auto-generated SBML file with URNs 573.50 KB Preview | Download
BIOMD0000000667.svg Auto-generated Reaction graph (SVG) 325.55 KB Preview | Download
BIOMD0000000667.sci Auto-generated Scilab file 47.07 KB Preview | Download
BIOMD0000000667-biopax3.owl Auto-generated BioPAX (Level 3) 410.94 KB Preview | Download
MODEL0848279215.sedml SED-ML file to produce figure 2. Model time units are seconds and not minutes. Y-axis: ERK_PP. 1.67 KB Preview | Download

  • Model originally submitted by : Vijayalakshmi Chelliah
  • Submitted: Apr 28, 2009 1:25:23 PM
  • Last Modified: Feb 1, 2018 9:57:43 AM
Revisions
  • Version: 3 public model Download this version
    • Submitted on: Feb 1, 2018 9:57:43 AM
    • Submitted by: administrator
    • With comment: Notes updated using online editor.
  • Version: 2 public model Download this version
    • Submitted on: Apr 28, 2009 1:25:23 PM
    • Submitted by: Vijayalakshmi Chelliah
    • With comment: Current version of Hornberg2005_MAPKsignalling
  • Version: 1 public model Download this version
    • Submitted on: Apr 28, 2009 1:25:23 PM
    • Submitted by: Vijayalakshmi Chelliah
    • With comment: Original import of Hornberg2005_MAPKsignalling
Curator's comment:
(added: 01 Feb 2018, 09:54:40, updated: 01 Feb 2018, 09:54:40)
?Figure 2 of the reference publication has been reproduced. The simulations were performed and plots were obtained using Copasi 4.19 (Build 140).