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Deactivation of src family kinases: Hypothesis testing using a Monte Carlo sensitivity analysis of systems-level properties

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 (2007) Deactivation of src family kinases: Hypothesis testing using a Monte Carlo sensitivity analysis of systems-level properties. JOURNAL OF COMPUTATIONAL BIOLOGY, 14 (9). pp. 1185-1200. [Journal article]

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DOI: 10.1089/cmb.2007.0095

Abstract

Src family tyrosine kinases play a key role in many cellular signalling networks, but due to the high complexity of these networks their precise function remains elusive. Many factors involved in Src regulation, such as specific kinases and phosphatases, are still unknown. Mathematical models have been constructed to improve the understanding of the system and its dynamic behavior. Using a computational random parameter search, we characterized and compared the dynamics of three alternative models in order to assess their likelihoods. For this, we investigated how systems-level properties such as bistability and excitable behavior relate to kinetic and physiological parameters and how robust these properties were. Our results suggest the existence of a putative negative feedback loop in the Src system. A previously suggested role for PTP. in the deactivation of Src was not supported by the model.

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 > Molecular Medicine
Biomedical Sciences Research Institute > Molecular Medicine > Nano Systems Biology
ID Code:3380
Deposited By:Professor Stephen Downes
Deposited On:15 Dec 2009 11:33
Last Modified:10 Jun 2010 10:23

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