Thebindingof?-arrestinstoagoNIST-occupiedGPCRstriggerstheassemblyofaMAPkinaseactivationcomplexusing?-arrestinasascaffold,withsubsequentactivationofa?-arrestin-boundpoolofERK1/2.Thereceptor—?-arrestin—ERKcomplexesarelocalizedtoendosomalvesicles,andtheirformationdoesnotresultinnucleartranslocationofactivatedERK1/2orstimulationofcellproliferation.Thefunctionof?-arrestin-boundERK1/2ispresentlyunknown.ActivationofERK1/2by?-arrestinscaffoldsmayfavorthephosphorylationofplasmamembrane,cytosolic,orcytoskeletalERK1/2substrates,oritmayleadtotranscriptionalactivationthroughtheERK-dependentactivationofotherkinases.Themodeldepicts?-arrestinscaffoldingoftheERK1/2MAPkinasecascade,basedupondataobtainedwiththeprotease-activatedPAR2andangiotensinAT1areceptors.AsimilarmechanismhasbeenproposedforregulationoftheJNK3MAPkinasecascadebyAT1areceptors.

Contributor:KosiGramatikoff,PhD

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