原创力文档a computational analysis of the dynamic roles of talin, dok1, and pipki for integrin activation计算分析蛋白的动态角色,dok1,pipki整合素激活.pdfVIP
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a computational analysis of the dynamic roles of talin, dok1, and pipki for integrin activation计算分析蛋白的动态角色,dok1,pipki整合素激活
A Computational Analysis of the Dynamic Roles of Talin,
Dok1, and PIPKI for Integrin Activation
¤
Florian Geier , Georgios Fengos, Dagmar Iber*
¨
Department of Biosystems Science and Engineering (D-BSSE), ETH Zurich, Basel, Switzerland
Abstract
Integrin signaling regulates cell migration and plays a pivotal role in developmental processes and cancer metastasis.
Integrin signaling has been studied extensively and much data is available on pathway components and interactions. Yet
the data is fragmented and an integrated model is missing. We use a rule-based modeling approach to integrate available
data and test biological hypotheses regarding the role of talin, Dok1 and PIPKI in integrin activation. The detailed
biochemical characterization of integrin signaling provides us with measured values for most of the kinetics parameters.
However, measurements are not fully accurate and the cellular concentrations of signaling proteins are largely unknown
and expected to vary substantially across different cellular conditions. By sampling model behaviors over the physiologically
realistic parameter range we find that the model exhibits only two different qualitative behaviors and these depend mainly
on the relative protein concentrations, which offers a powerful point of control to the cell. Our study highlights the
necessity to characterize model behavior not for a single parameter optimum, but to identify parameter sets that
characterize different signaling modes.
Citation: Geier F, Fengos G, Iber D (2011) A Computational Analysis of the Dynamic Roles of Talin, Dok1, and PIPKI for Integrin Activation. PLoS ONE 6(11):
e24808. doi:10.1371/journal.pone.0024808
Editor: Raya Kha
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