InteractionofTcellreceptorwithspecificantigeninthecontextofMHCIIactivatesasignaltransductionpathwaythatleadstoTcellactivation.IntheTcellreceptorsignalingpathway,thesrcfamilykinasesLckandFynareactivatedtophosphorylateproteinsintheTcellreceptorcomplexwhichrecruitandactivatetheZAP70kinase.TheactivationofZAP70phosphorylatesdownstreamtargetsthatactivateMAPkinasepathwaysandcauseTcellactivation.TheCD45phosphorylasealsoplaysaroleinTcellreceptorsignaling,dephosphorylatedLckandFyntoactivatethem.OtherfactorsmodulateTcellreceptoractivation.Csk(COOH-terminalSrkkinase)phosphorylatesLckanddeactivatesit,opposingtheactionofCD45.ThephosphorylationofLckbyCskinhibitsTcellreceptorsignalingandinhibitsTcellactivation.CskactivityisregulatedinTcellsbyPKA,thecAMP-dependentproteinkinaseactivatedbythesecondmessengercAMP.TheactivityofCskalsoappearstodependonotherfactorssuchasCBP,whichrecruitsCsktotheplasmamembraneinlipidraftswhereothersignalingfactorssuchtheTcellreceptorcomplexarelocalized.CBPalsodirectlyactivatesCsk.

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REFERENCES:Chow,L.M.,Fournel,M.,Davidson,D.,andVeillette,A.NegativeregulationofT-cellreceptorsignallingbytyrosineproteinkinasep50csk.Nature1993,365(6442),156-60Kawabuchi,M.etal.TransmembranephosphoproteinCbpregulatestheactivitiesofSrc-familytyrosinekinases.Nature2000,404(6781),999-1003Takeuchi,S.etal.TransmembranephosphoproteinCbppositivelyregulatestheactivityofthecarboxyl-terminalSrckinase,Csk.J.Biol.Chem.2000,275(38),29183-6Vang,T.etal.ActivationoftheCOOH-terminalSrckinase(Csk)bycAMP-dependentproteinkinaseinhibitssignalingthroughtheTcellreceptor.J.Exp.Med.2001,193(4),497-507

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