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dc.contributor.authorTinti, Michele
dc.contributor.authorJohnson, Catherine
dc.contributor.authorToth, Rachel
dc.contributor.authorFerrier, David Ellard Keith
dc.contributor.authorMacKintosh, Carol
dc.identifier.citationTinti , M , Johnson , C , Toth , R , Ferrier , D E K & MacKintosh , C 2012 , ' Evolution of signal multiplexing by 14-3-3-binding 2R-ohnologue protein families in the vertebrates ' , Open Biology , vol. 2 , 120103 .
dc.identifier.otherPURE: 24998691
dc.identifier.otherPURE UUID: 184c6da7-dc5b-4bfa-8b87-b6460a87c92e
dc.identifier.otherScopus: 84873901523
dc.identifier.otherORCID: /0000-0003-3247-6233/work/36423827
dc.descriptionThis work was supported by the UK Medical Research Council via a Developmental Pathway Funding Scheme award and a Research Councils UK fellowship in marine biology.en
dc.description.abstract14-3-3 proteins regulate cellular responses to stimuli by docking onto pairs of phosphorylated residues on target proteins. The present study shows that the human 14-3-3-binding phosphoproteome is highly enriched in 2R-ohnologues, which are proteins in families of two to four members that were generated by two rounds of whole genome duplication at the origin of the vertebrates. We identify 2R-ohnologue families whose members share a ‘lynchpin’, defined as a 14-3-3-binding phosphosite that is conserved across members of a given family, and aligns with a Ser/Thr residue in pro-orthologues from the invertebrate chordates. For example, the human receptor expression enhancing protein (REEP) 1–4 family has the commonest type of lynchpin motif in current datasets, with a phosphorylatable serine in the –2 position relative to the 14-3-3-binding phosphosite. In contrast, the second 14-3-3-binding sites of REEPs 1–4 differ and are phosphorylated by different kinases, and hence the REEPs display different affinities for 14-3-3 dimers. We suggest a conceptual model for intracellular regulation involving protein families whose evolution into signal multiplexing systems was facilitated by 14-3-3 dimer binding to lynchpins, which gave freedom for other regulatory sites to evolve. While increased signalling complexity was needed for vertebrate life, these systems also generate vulnerability to genetic disorders.
dc.relation.ispartofOpen Biologyen
dc.rights© 2012 The Authors. Published by the Royal Society under the terms of the Creative Commons Attribution License, which permits unrestricted use, provided the original author and source are credited.en
dc.subjectHereditary spastic paraplegiaen
dc.subjectQH301 Biologyen
dc.titleEvolution of signal multiplexing by 14-3-3-binding 2R-ohnologue protein families in the vertebratesen
dc.typeJournal articleen
dc.description.versionPublisher PDFen
dc.contributor.institutionUniversity of St Andrews.School of Biologyen
dc.contributor.institutionUniversity of St Andrews.Scottish Oceans Instituteen
dc.contributor.institutionUniversity of St Andrews.Marine Alliance for Science & Technology Scotlanden
dc.description.statusPeer revieweden

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