An Investigation of Hierachical Protein Recruitment to the Inhibitory Platelet Receptor, G6B-b 英文参考文献.docVIP
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An Investigation of Hierachical Protein Recruitment to the Inhibitory Platelet Receptor, G6B-b 英文参考文献
AnInvestigationofHierachicalProteinRecruitmentto
theInhibitoryPlateletReceptor,G6B-b
CarmenH.Coxon1*,AmandaJ.Sadler1,JiandongHuo2,R.DuncanCampbell1*
1DepartmentofPhysiology,AnatomyandGenetics,UniversityofOxford,Oxford,UnitedKingdom,2WeatherallInstituteofMolecularMedicine,UniversityofOxford,
JohnRadcliffeHospital,Headington,Oxford,UnitedKingdom
Abstract
Platelet activation is regulated by both positive and negative signals. G6B-b is an inhibitory platelet receptor with an
immunoreceptor tyrosine-based inhibitory motif (ITIM) and an immunoreceptor tyrosine-based switch motif (ITSM). The
molecularbasisofinhibitionbyG6B-biscurrentlyunknownbutthoughttoinvolvetheSH2domain-containingtyrosine
phosphatase SHP-1. Here we show that G6B-b also associates with SHP-2, as well as SHP-1, in human platelets. Using a
numberofbiochemicalapproaches,wefoundtheseinteractionstobedirectandthatthetandemSH2domainsofSHP-2
demonstratedabindingaffinityforG6B-b100-foldhigherthanthatofSHP-1.ItwasalsoobservedthatwhileSHP-1hasan
absoluterequirementforphosphorylationatbothmotifstobind,SHP-2canassociatewithG6B-bwhenonlyonemotifis
phosphorylated,withtheN-terminalSH2domainandtheITIMbeingmostimportantfortheinteraction.Anumberofother
previouslyunreportedSH2domain-containingproteins,includingSykandPLCc2,alsodemonstratedspecificityforG6B-b
phosphomotifsandmayservetoexplaintheobservationthatG6B-bremainsinhibitoryintheabsenceofbothSHP-1and
SHP-2.Inaddition,thepresenceofdualphosphorylatedG6B-binwashedhumanplateletscanreducetheEC50forbothCRP
andcollagen.
Citation:CoxonCH,SadlerAJ,HuoJ,CampbellRD(2012)AnInvestigationofHierachicalProteinRecruitmenttotheInhibitoryPlateletReceptor,G6B-b.PLoS
ONE7(11):e49543.doi:10.1371/journal.pone.0049543
Editor:LaszloBuday,HungarianAcademyofSciences,Hungary
ReceivedFebruary22,2012;AcceptedOctober9,2012;PublishedNovember19,2012
Copyright: ? 2012 Coxon et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits
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