The Stochastic Behavior of a Molecular Switching Circuit with Feedback

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The Stochastic Behavior of a Molecular Switching Circuit with Feedback

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dc.contributor.author Krishnamurthy, Supriya
dc.contributor.author Krakauer, David
dc.contributor.author Smith, Eric
dc.contributor.author Fontana, Walter
dc.date.accessioned 2011-04-01T14:49:37Z
dc.date.issued 2007
dc.identifier.citation Krishnamurthy, Supriya, Eric Smith, David Krakauer, and Walter Fontana. 2007. The stochastic behavior of a molecular switching circuit with feedback. Biology Direct 2: 13. en_US
dc.identifier.issn 1745-6150 en_US
dc.identifier.uri http://nrs.harvard.edu/urn-3:HUL.InstRepos:4789783
dc.description.abstract Background: Using a statistical physics approach, we study the stochastic switching behavior of a model circuit of multisite phosphorylation and dephosphorylation with feedback. The circuit consists of a kinase and phosphatase acting on multiple sites of a substrate that, contingent on its modification state, catalyzes its own phosphorylation and, in a symmetric scenario, dephosphorylation. The symmetric case is viewed as a cartoon of conflicting feedback that could result from antagonistic pathways impinging on the state of a shared component. Results: Multisite phosphorylation is sufficient for bistable behavior under feedback even when catalysis is linear in substrate concentration, which is the case we consider. We compute the phase diagram, fluctuation spectrum and large-deviation properties related to switch memory within a statistical mechanics framework. Bistability occurs as either a first-order or second-order non-equilibrium phase transition, depending on the network symmetries and the ratio of phosphatase to kinase numbers. In the second-order case, the circuit never leaves the bistable regime upon increasing the number of substrate molecules at constant kinase to phosphatase ratio. Conclusion: The number of substrate molecules is a key parameter controlling both the onset of the bistable regime, fluctuation intensity, and the residence time in a switched state. The relevance of the concept of memory depends on the degree of switch symmetry, as memory presupposes information to be remembered, which is highest for equal residence times in the switched states. Reviewers: This article was reviewed by Artem Novozhilov (nominated by Eugene Koonin), Sergei Maslov, and Ned Wingreen. en_US
dc.language.iso en_US en_US
dc.publisher BioMed Central en_US
dc.relation.isversionof doi:10.1186/1745-6150-2-13 en_US
dc.relation.hasversion http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1904185/pdf/ en_US
dash.license LAA
dc.subject activated protein-kinase en_US
dc.subject dual phosphorylation en_US
dc.subject gene-expression en_US
dc.subject cell en_US
dc.subject noise en_US
dc.subject bistability en_US
dc.subject networks en_US
dc.subject cascades en_US
dc.subject dynamics en_US
dc.subject enzyme en_US
dc.title The Stochastic Behavior of a Molecular Switching Circuit with Feedback en_US
dc.type Journal Article en_US
dc.description.version Version of Record en_US
dc.relation.journal Biology Direct en_US
dash.depositing.author Fontana, Walter
dc.date.available 2011-04-01T14:49:37Z
dash.affiliation.other HMS^Systems Biology en_US

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