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  Multistability of signal transduction motifs

Saez-Rodriguez, J., Hammerle-Fickinger, A., Dalal, O., Klamt, S., Gilles, E. D., & Conradi, C. (2008). Multistability of signal transduction motifs. IET Systems Biology, 2(2), 80-93. doi:10.1049/iet-syb:20070012.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0013-95F4-B Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0027-C1E8-1
Genre: Journal Article

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 Creators:
Saez-Rodriguez, J.1, 2, Author              
Hammerle-Fickinger, A.1, 3, Author              
Dalal, O.4, Author
Klamt, S.1, Author              
Gilles, E. D.1, Author              
Conradi, C.5, Author              
Affiliations:
1Systems Biology, Max Planck Institute for Dynamics of Complex Technical Systems, Max Planck Society, ou_1738155              
2Harvard Medical School, ou_persistent22              
3Centre of Life and Food Sciences Weihenstephan, TU Munich, Germany, persistent:22              
4Indian Institute of Technology, Bombay, Mumbai 400076, India, ou_persistent22              
5Systems and Control Theory, Max Planck Institute for Dynamics of Complex Technical Systems, Max Planck Society, ou_1738154              

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 Abstract: Protein domains are the basic units of signalling processes. The mechanisms they are involved in usually follow recurring patterns, such as phosphorylation / dephosphorylation cycles. In this contribution, a set of common motifs was defined and their dynamic models were analysed with respect to number and stability of steady states. In a first step Feinberg's Chemical Reaction Network Theory was used to determine whether a motif can show multistationarity or not. The analysis revealed that, apart from double-step activation motifs including a distributive mechanism, only those motifs involving an autocatalytic reaction can show multistationarity. To further characterise these motifs, a large number of randomly chosen parameter sets leading to bistability was generated, followed by a bifurcation analysis for each parameter set and a statistical evaluation of the results. The statistical results can be used to explore robustness against noise, pointing to the observation that multistationarity {at the single-motif level} may not be a robust property: the range of protein concentrations compatible with multistationarity is fairly narrow. Furthermore, experimental evidence suggests that protein concentrations vary substantially between cells. Considering a motif designed to be a bistable switch, this implies that fluctuation of protein concentrations between cells would prevent a significant proportion of motifs to act as a switch. We consider this work as a first step towards a catalogue of fully characterised signalling modules. copyright: The Institution of Engineering and Technology 2008 [accessed 2013 June 14th]

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Language(s): eng - English
 Dates: 2008
 Publication Status: Published in print
 Pages: -
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 Rev. Method: Peer
 Identifiers: DOI: 10.1049/iet-syb:20070012
eDoc: 324184
Other: 41/08
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Title: IET Systems Biology
Source Genre: Journal
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Pages: - Volume / Issue: 2 (2) Sequence Number: - Start / End Page: 80 - 93 Identifier: -