Hornberg, Binder, Bruggeman, Schoeberl, Heinrich, Westerhoff, 2005

Model Status

This CellML model runs in both PCENv and COR to recreate the published results. Thank you to the model author Jorrit Hornberg for providing us with the original mathematica code, and also to Joe Cursons for the hours he has spent debugging the CellMl model.

There are several differences between the original CellML version of this model (which was based on the published paper), and the current version of the model (which was based on the Mathematica code). These differences are listed here as a PDF document.

Model Structure

The epidermal growth factor receptor (EGFR) is a protein-tyrosine kinase receptor which regulates cell growth, survival, proliferation, and differentiation. When epidermal growth factor (EGF) binds to EGFR is causes receptor dimerisation and activates its kinase activity, leading to autophosphorylation. In turn, this leads to a range of cytoplasmic proteins with specific binding domains, binding to the activated EGFR, and then themselves becoming phosphorylated and activated. This then leads to further propagation of the signal through several interacting signal transduction pathways.

Although there is a large body of data which describes EGFR signalling at the molecular level, the mechanisms underlying the regulation of the cellular responses to EGF remain poorly understood. A contributing factor to this relatively poor understanding is the absence of a quantitative description of the EGFR signalling network. Placing the experimental data within the framework of a mathematical model provides a method of quantitatively analysing the available experimental data. In the paper described here, Hornberg et al. develop a mathematical model which presents a quantitative description of MAPK signalling (see figure below).

The kinetic model predicts how the cellular response is controlled by the relative levels and activity states of the signalling proteins, and also determines the conditions under which activation patterns are transient or sustained. This modelling analysis will facilitate the assessment of how the EGFR signalling system can process information and generate distinct outputs in response to stimuli.

The complete original paper reference is cited below:

Control of MAPK signalling: from complexity to what really matters, Jorrit J Hornberg, Bernd Binder, Frank J Bruggeman, Birgit Schoeberl, Reinhart Heinrich and Hans V Westerhoff, 2005, Oncogene, 26, 117-125. PubMed ID: 16007170

Schematic diagram of the signal transduction nectwork described by the model.