Roles of the Src Tyrosine Kinases Lck and Fyn in Regulating γδTCR Signal Strength 英文参考文献.docVIP

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Roles of the Src Tyrosine Kinases Lck and Fyn in Regulating γδTCR Signal Strength 英文参考文献.doc

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RolesoftheSrcTyrosineKinasesLckandFynin RegulatingcdTCRSignalStrength ReneeM.Laird,SandraM.Hayes* DepartmentofMicrobiologyandImmunology,SUNYUpstateMedicalUniversity,Syracuse,NewYork,UnitedStatesofAmerica Abstract LckandFyn,membersoftheSrcfamilyoftyrosinekinases,arekeycomponentsoftheabTCR-coupledsignalingpathway. WhileitisgenerallyacceptedthatbothLckandFynpositivelyregulatesignaltransductionbytheabTCR,recentstudies haveshownthatLckandFynhavedistinctfunctionsinthissignalingpathway,withLckbeingapositiveregulatorandFyn being a negative regulator of abTCR signal transduction. To determine whether Lck and Fyn also differentially regulate cdTCRsignaltransduction,weanalyzedcdTcelldevelopmentandfunctioninmicewithreducedLckorFynexpression levels.WefoundthatreducingLckorFynlevelsalteredthestrengthofthecdTCRsignalingresponse,withlowlevelsofLck weakeningcdTCRsignalstrengthandlowlevelsofFynaugmentingcdTCRsignalstrength.ThesealterationsincdTCRsignal strengthhadprofoundeffectsnotonlyonab/cdlineagechoice,butalsooncdthymocytematurationandcdTcelleffector function.TheseresultsindicatethatthecellularlevelsofLckandFynplayaroleinregulatingthestrengthofthecdTCR signalingresponseatdifferentstagesinthelifeofthecdTcell. Citation: Laird RM, Hayes SM (2010) Roles ofthe Src Tyrosine Kinases Lck and Fyn in Regulating cdTCR Signal Strength. PLoS ONE 5(1): e8899. doi:10.1371/ journal.pone.0008899 Editor:JoseAlberola-Ila,OklahomaMedicalResearchFoundation,UnitedStatesofAmerica ReceivedNovember27,2009;AcceptedJanuary6,2010;PublishedJanuary26,2010 Copyright: ? 2010 Laird, Hayes. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalauthorandsourcearecredited. Funding:ThisworkwassupportedinpartbytheHendricksFundforMedicalResearchawardedtoS.M.H.Thefundershadnoroleinstudydesign,datacollection andanalysis,decisiontopublish,orpreparationofthemanuscript. CompetingIntere