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Bistable switching and excitable behaviour in the activation of Src at mitosis

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 (2006) Bistable switching and excitable behaviour in the activation of Src at mitosis. BIOINFORMATICS, 22 (14). E158-E165. [Journal article]

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DOI: 10.1093/bioinformatics/btl201

Abstract

Motivation: The protein tyrosine kinase Src is involved in a multitude of biochemical pathways and cellular functions. A complex network of interactions with other kinases and phosphatases obscures its precise mode of operation. Results: We have constructed a semi-quantitative computational dynamic systems model of the activation of Src at mitosis based on protein interactions described in the literature. Through numerical simulation and bifurcation analysis we show that Src regulation involves a bistable switch, a pattern increasingly recognised as essential to biochemical signalling. The switch is operated by the tyrosine kinase CSK, which itself is involved in a negative feedback loop with Src. Negative feedback generates an excitable system, which produces transient activation of Src. One of the system parameters, which is linked to the cyclin dependent kinase cdc2, controls excitability via a second bistable switch. This topology allows for differentiated responses to a multitude of signals. The model offers explanations for the existence of the positive and negative feedback loops involving protein tyrosine phosphatase alpha (PTPa) and translocation of CSK and predicts a specific relationship between Src phosphorylation and activity.

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:3516
Deposited By:Professor Stephen Downes
Deposited On:15 Dec 2009 14:36
Last Modified:15 Jun 2010 15:09

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