Thebindingof?-arrestinstoagoNIST-occupiedGPCRscoincideswiththerecruitmentofSrcfamilytyrosinekinases,includingc-Src,Hckandc-Fgr(Src-TK),tothereceptor—?-arrestincomplex.Severalsignalingeventshavebeenreportedtoinvolve?-arrestin-dependentSrcrecruitment.Theseincludetheregulationofclathrin-dependent?2-adrenergicreceptorendocytosisbytyrosinephosphorylationofdynamin,Ras-dependentactivationoftheERK1/2MAPkinasecascadeandstimulationofcellproliferationby?2-adrenergicandneurokininNK1receptors,andstimulationofchemokineCXCR1receptor-mediatedneutrophildegranulation Contributor:KosiGramatikoff,PhD REFERENCES:AndrewJetal.PhysiologicalRegulationofGProtein-LinkedSignalingPhysiolRev,Oct1999;79:1373-1430.K.Palczewski.StructureandfunctionsofarrestinsProteinSci.,Sep1994;3:1355-1361.KLPierceandRJLefkowitz.Classicalandnewrolesofbeta-arrestinsintheregulationofG-protein-coupledreceptors.NatRevNeurosci,Oct2001;2(10):727-33.MoritzBünemannandM.MarleneHosey.G-proteincoupledreceptorkinasesasmodulatorsofG-proteinsignalingJ.Physiol.,May1999;517:5-23.RobertJ.Lefkowitz.GProtein-coupledReceptors.III.Newrolesforreceptorkinasesand-arrestinsinreceptorsignalinganddesensitization.J.Biol.Chem.,Jul1998;273:18677-18680.
