Proteomic and Phospho-Proteomic Profile of Human Platelets in Basal, Resting State Insights into Integrin Signaling 英文参考文献.docVIP

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Proteomic and Phospho-Proteomic Profile of Human Platelets in Basal, Resting State Insights into Integrin Signaling 英文参考文献.doc

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Proteomic and Phospho-Proteomic Profile of Human Platelets in Basal, Resting State Insights into Integrin Signaling 英文参考文献

ProteomicandPhospho-ProteomicProfileofHuman PlateletsinBasal,RestingState:InsightsintoIntegrin Signaling AmirH.Qureshi1,2.,VineetChaoji3.,DonyMaiguel2,MohdHafeezFaridi2,ConstantinosJ.Barth2, SaeedM.Salem3,MuditaSinghal4,DarrenStoub5,BryanKrastins6,MitsunoriOgihara7,MohammedJ. Zaki3,VineetGupta1,2* 1Nephrology Division, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States of America, 2Division of Nephrology and Hypertension,DepartmentofMedicine,UniversityofMiami,Miami,Florida,UnitedStatesofAmerica,3DepartmentofComputerScience,RensselaerPolytechnicInstitute, Troy,NewYork,UnitedStatesofAmerica,4ComputationalBiologyandBioinformaticsGroup,ComputationalandInformationalSciencesDirectorate,PacificNorthwest NationalLaboratory,Richland,Washington,UnitedStatesofAmerica,5DepartmentofChemistry,RollinsCollege,WinterPark,Orlando,Florida,UnitedStatesofAmerica, 6Thermo-Fisher BRIMS Center, Cambridge, Massachusetts, United States of America, 7Department of Computer Science, University of Miami, Miami, Florida, United StatesofAmerica Abstract Duringatherogenesisandvascularinflammationquiescentplateletsareactivatedtoincreasethesurfaceexpressionand ligand affinity of the integrin aIIbb3 via inside-out signaling. Diverse signals such as thrombin, ADP and epinephrine transducesignalsthroughtheirrespectiveGPCRstoactivateproteinkinasesthatultimatelyleadtothephosphorylationof thecytoplasmictailoftheintegrinaIIbb3andaugmentitsfunction.Thesignalingpathwaysthattransmitsignalsfromthe GPCRtothecytosolicdomainoftheintegrinarenotwelldefined.Inanefforttobetterunderstandthesepathways,we employedacombinationofproteomicprofilingandcomputationalanalysesofisolatedhumanplatelets.Weanalyzedten independenthumansamplesandidentifiedatotalof1507uniqueproteinsinplatelets.Thisisthemostcomprehensive plateletproteomeassembledtodateandincludes190membrane-associatedand262phosphorylatedproteins,whichwere identifiedviaindependentproteomicandphospho-proteomicprofiling.Weusedthi