Quantification of EGF Receptor Signalling |  PDF |
Catherine Lloyd (Bioengineering Institute, University of Auckland)
Table of Contents
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, Kholodenko et al. develop a mathematical model which presents a quantitative description of short term EGFR signalling (see Figure 1 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 model has been described here in CellML (the raw CellML description of the Kholodenko et al. 1999 model can be downloaded in various formats as described in the section “Download This Model”).
The complete original paper reference is cited below:
Quantification of Short Term Signaling by the Epidermal Growth Factor Receptor, Boris N. Kholodenko, Oleg V. Demin, Gisela Moehren, and Jan B. Hoek, 1999, The Journal of Biological Chemistry, 274, 30169-30181. (Full text (HTML) and PDF versions of the article are available on The Journal of Biological Chemistry website.) PubMed ID: 10514507
kholodenko_model_1999.xml — the raw XML.
kholodenko_model_1999.html — an HTML version for browsing online.
kholodenko_model_1999.pdf — a PDF version suitable for printing.
cellml_kholodenko_model_1999.tar.gz — a gzipped tarball with the XML and this documentation.
kholodenko_model_1999_maths.pdf — a PDF of the equations described in the model generated directly from the CellML description using the MathML Renderer.
