BIOPHYSICAL THEORY AND MODELING |
Src family kinases and receptors: analysis of three activation mechanisms by dynamic systems modelling
Hendrik FuB 1*, Werner Dubitzky 1, C. Stephen Downes 1 and Mary Jo Kurth 1
1 University of Ulster
* To whom correspondence should be addressed. E-mail: fuss-h{at}ulster.ac.uk.
Submitted on June 19, 2007
Revised on August 31, 2007
Accepted on 29 October 2007
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Abstract |
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Src family kinases (SFKs) interact with a number of cellular receptors. They participate in diverse signalling pathways and cellular functions. Most of the receptors involved in SFK signalling are characterised by similar modes of regulation. This computational study discusses a general kinetic model of SFK-receptor interaction. The analysis of the model revealed three major ways of SFK activation: release of inhibition by Csk, weakening of the inhibitory intra-molecular phosphotyrosine-SH2 interaction and amplification of a stimulating kinase activity. The SFK model was then extended to simulate interaction with growth factor and T cell receptors. The modular SFK signalling system was shown to adapt to the requirements of specific signalling contexts and yield qualitatively different responses in the different simulated environments. The model also provides a systematic overview of the major interactions between SFKs and various cellular signalling systems and identifies their common properties.
Key Words:
Cbp/PAG, Growth factor receptors, Non-linear dynamics, Receptor tyrosine kinases, T cell receptor, Tyrosine phosphorylation
