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Src family kinases and receptors: Analysis of three activation mechanisms by dynamic systems modeling

Biomedical Sciences Research Institute Computer Science Research Institute Environmental Sciences Research Institute Nanotechnology & Advanced Materials Research Institute

Fuss, Hendrik, Dubitzky, Werner, Downes, Stephen and Kurth, Mary Jo (2008) Src family kinases and receptors: Analysis of three activation mechanisms by dynamic systems modeling. BIOPHYSICAL JOURNAL, 94 (6). pp. 1995-2006. [Journal article]

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DOI: 10.1529/biophysj.107.115022

Abstract

Src family kinases (SFKs) interact with a number of cellular receptors. They participate in diverse signaling pathways and cellular functions. Most of the receptors involved in SFK signaling are characterized by similar modes of regulation. This computational study discusses a general kinetic model of SFK-receptor interaction. The analysis of the model reveals three major ways of SFK activation: release of inhibition by C-terminal Src kinase, weakening of the inhibitory intramolecular 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 signaling system was shown to adapt to the requirements of specific signaling 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 signaling systems and identifies their common properties.

Item Type:Journal article
Faculties and Schools:Faculty of Life and Health Sciences
Faculty of Life and Health Sciences > School of Biomedical Sciences
Research Institutes and Groups:Biomedical Sciences Research Institute
Biomedical Sciences Research Institute > Infection and Immunity/Microbiology
Biomedical Sciences Research Institute > Molecular Medicine
Biomedical Sciences Research Institute > Molecular Medicine > Nano Systems Biology
ID Code:3377
Deposited By:Professor Stephen Downes
Deposited On:15 Dec 2009 11:30
Last Modified:15 Jun 2010 15:04

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