A computational analysis of the dynamic roles of talin, Dok1, and PIPKI for integrin activation.

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...

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Autores principales:	Florian Geier, Georgios Fengos, Dagmar Iber
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/07ea5036eed542188cd170c6139b6350
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spelling	oai:doaj.org-article:07ea5036eed542188cd170c6139b63502021-11-18T07:34:15ZA computational analysis of the dynamic roles of talin, Dok1, and PIPKI for integrin activation.1932-620310.1371/journal.pone.0024808https://doaj.org/article/07ea5036eed542188cd170c6139b63502011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22110576/?tool=EBIhttps://doaj.org/toc/1932-6203Integrin 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.Florian GeierGeorgios FengosDagmar IberPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 11, p e24808 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Florian Geier Georgios Fengos Dagmar Iber A computational analysis of the dynamic roles of talin, Dok1, and PIPKI for integrin activation.
description	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.
format	article
author	Florian Geier Georgios Fengos Dagmar Iber
author_facet	Florian Geier Georgios Fengos Dagmar Iber
author_sort	Florian Geier
title	A computational analysis of the dynamic roles of talin, Dok1, and PIPKI for integrin activation.
title_short	A computational analysis of the dynamic roles of talin, Dok1, and PIPKI for integrin activation.
title_full	A computational analysis of the dynamic roles of talin, Dok1, and PIPKI for integrin activation.
title_fullStr	A computational analysis of the dynamic roles of talin, Dok1, and PIPKI for integrin activation.
title_full_unstemmed	A computational analysis of the dynamic roles of talin, Dok1, and PIPKI for integrin activation.
title_sort	computational analysis of the dynamic roles of talin, dok1, and pipki for integrin activation.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/07ea5036eed542188cd170c6139b6350
work_keys_str_mv	AT floriangeier acomputationalanalysisofthedynamicrolesoftalindok1andpipkiforintegrinactivation AT georgiosfengos acomputationalanalysisofthedynamicrolesoftalindok1andpipkiforintegrinactivation AT dagmariber acomputationalanalysisofthedynamicrolesoftalindok1andpipkiforintegrinactivation AT floriangeier computationalanalysisofthedynamicrolesoftalindok1andpipkiforintegrinactivation AT georgiosfengos computationalanalysisofthedynamicrolesoftalindok1andpipkiforintegrinactivation AT dagmariber computationalanalysisofthedynamicrolesoftalindok1andpipkiforintegrinactivation
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A computational analysis of the dynamic roles of talin, Dok1, and PIPKI for integrin activation.

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