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Please use this identifier to cite or link to this item: http://hdl.handle.net/10023/3022
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Title: Evolution of signal multiplexing by 14-3-3-binding 2R-ohnologue protein families in the vertebrates
Authors: Tinti, Michele
Johnson, Catherine
Toth, Rachel
Ferrier, David Ellard Keith
MacKintosh, Carol
Keywords: Branchiostoma
Ciona
Hereditary spastic paraplegia
RAB3GAP1
RAB3GAP2
QH301 Biology
Issue Date: Jul-2012
Citation: Tinti , 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 .
Abstract: 14-3-3 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.
Version: Publisher PDF
Description: This 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.
Status: Peer reviewed
URI: http://hdl.handle.net/10023/3022
DOI: http://dx.doi.org/10.1098/rsob.120103
ISSN: 2046-2441
Type: Journal article
Rights: © 2012 The Authors. Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/3.0/, which permits unrestricted use, provided the original author and source are credited.
Appears in Collections:University of St Andrews Research
Biology Research
Scottish Oceans Institute Research



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