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Multistability of signal transduction motifs

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Title Multistability of signal transduction motifs
 
Creator SAEZ-RODRIGUEZ, J
HAMMERLE-FICKINGER, A
DALAL, O
KLAMT, S
GILLES, ED
CONRADI, C
 
Subject complex isothermal reactors
chemical-reaction networks
multiple steady-states
gene-expression
deficiency-one
combinatorial complexity
systems biology
single-cell
models
phosphorylation
 
Description Protein domains are the basic units of signalling processes. The mechanisms they are involved in usually follow recurring patterns, such as phosphorylation/dephosphorylation cycles. 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 of 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 from acting as a switch. The authors consider this to be a first step towards a catalogue of fully characterised signalling modules.
 
Publisher INST ENGINEERING TECHNOLOGY-IET
 
Date 2011-08-03T07:48:40Z
2011-12-26T12:54:06Z
2011-12-27T05:41:30Z
2011-08-03T07:48:40Z
2011-12-26T12:54:06Z
2011-12-27T05:41:30Z
2008
 
Type Article
 
Identifier IET SYSTEMS BIOLOGY, 2(2), 80-93
1751-8849
http://dx.doi.org/10.1049/iet-syb:20070012
http://dspace.library.iitb.ac.in/xmlui/handle/10054/8950
http://hdl.handle.net/10054/8950
 
Language en