Spatiotemporal control of cyclic AMP immunomodulation through the PKA–Csk inhibitory pathway is achieved by anchoring to an Ezrin–EBP50–PAG scaffold in effector T cells

摘要

AvarietyofimmunoregulatorysignalstoeffectorTcellsfrommonocytes,macrophagesandregulatoryTcellsactthroughcyclicadenosinemonophosphate.IntheeffectorTcell,theproteinkinaseA(PKA)typeIisoenzymelocalizestolipidraftsduringTcellactivationandmodulatesdirectlytheproximaleventsthattakeplaceafterengagementoftheTcellreceptor.ThemostproximaltargetforPKAphosphorylationisC‐terminalSrckinase(Csk),whichinitiatesanegativesignalpathwaythatfine‐tunestheTcellactivationprocess.TheAkinaseanchoringproteinEzrincolocalizesPKAandCskbyformingasupramolecularsignalingcomplexconsistingofPKA,Ezrin,Ezrin/radixin/moesin(ERM)bindingproteinof50kDa(EBP50),phosphoproteinassociatedwithglycosphingolipid‐enrichedmembranemicrodomains(GEMs)(PAG)andCsk...