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dc.contributor.authorSiryaporn, Albert
dc.contributor.authorGoulian, Mark
dc.contributor.authorPerchuk, Barrett
dc.contributor.authorLaub, Michael T.
dc.date.accessioned2014-02-07T14:34:09Z
dc.date.available2014-02-07T14:34:09Z
dc.date.issued2010-12
dc.date.submitted2010-06
dc.identifier.issn1744-4292
dc.identifier.urihttp://hdl.handle.net/1721.1/84667
dc.description.abstractWe have evolved a robust two‐component signal transduction pathway from a sensor kinase (SK) and non‐partner response regulator (RR) that show weak cross‐talk in vitro and no detectable cross‐talk in vivo in wild‐type strains. The SK, CpxA, is bifunctional, with both kinase and phosphatase activities for its partner RR. We show that by combining a small number of mutations in CpxA that individually increase phosphorylation of the non‐partner RR OmpR, phosphatase activity against phospho‐OmpR emerges. The resulting circuit also becomes responsive to input signal to CpxA. The effects of combining these mutations in CpxA appear to reflect complex intragenic interactions between multiple sites in the protein. However, by analyzing a simple model of two‐component signaling, we show that the behavior can be explained by a monotonic change in a single parameter controlling protein–protein interaction strength. The results suggest one possible mode of evolution for two‐component systems with bifunctional SKs whereby the remarkable properties and competing reactions that characterize these systems can emerge by combining mutations of the same effect.en_US
dc.description.sponsorshipNational Science Foundation (U.S.). Materials Research Science and Engineering Centers (Program) (Award DMR0520020)en_US
dc.language.isoen_US
dc.publisherNature Publishing Groupen_US
dc.relation.isversionofhttp://dx.doi.org/10.1038/msb.2010.105en_US
dc.rightsCreative Commons Attribution‐NonCommercial Licenseen_US
dc.rights.urihttp://creativecommons.org/licenses/by-nc/3.0/en_US
dc.sourceNatureen_US
dc.titleEvolving a robust signal transduction pathway from weak cross-talken_US
dc.typeArticleen_US
dc.identifier.citationSiryaporn, Albert, Barrett S Perchuk, Michael T Laub, and Mark Goulian. “Evolving a robust signal transduction pathway from weak cross-talk.” Molecular Systems Biology 6 (December 21, 2010). Copyright © 2010 EMBO and Macmillan Publishers Limiteden_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biologyen_US
dc.contributor.mitauthorPerchuk, Barretten_US
dc.contributor.mitauthorLaub, Michael T.en_US
dc.relation.journalMolecular Systems Biologyen_US
dc.eprint.versionFinal published versionen_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dspace.orderedauthorsSiryaporn, Albert; Perchuk, Barrett S; Laub, Michael T; Goulian, Marken_US
dc.identifier.orcidhttps://orcid.org/0000-0002-8288-7607
mit.licensePUBLISHER_CCen_US


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