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Determination of EGFR Endocytosis Kinetic by Auto-Regulatory Association of PLD1 with μ2 英文参考文献.docVIP

Determination of EGFR Endocytosis Kinetic by Auto-Regulatory Association of PLD1 with μ2 英文参考文献.doc

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Determination of EGFR Endocytosis Kinetic by Auto-Regulatory Association of PLD1 with μ2 英文参考文献

DeterminationofEGFREndocytosisKineticby Auto-RegulatoryAssociationofPLD1withm2 JunSungLee1,IlShinKim1,JungHwanKim1,WonhwaCho2,Pann-GhillSuh1,SungHoRyu1* 1DivisionofMolecularandLifeSciences,PohangUniversityofScienceandTechnology,Pohang,Kyungbuk,RepublicofKorea,2DepartmentofChemistry,Universityof IllinoisatChicago,Chicago,Illinois,UnitedStatesofAmerica Abstract Background:Uponligandbinding,cellsurfacesignalingreceptorsareinternalizedthroughaprocesstightlyregulatedby endocytic proteins and adaptor protein 2 (AP2) to orchestrate them. Although the molecular identities and roles of endocyticproteinsarebecomingclearer,itisstillunclearwhatdeterminesthereceptorendocytosiskineticswhichismainly regulatedbytheaccumulationofendocyticapparatustotheactivatedreceptors. Methodology/PrincipalFindings:Hereweemployedthekineticanalysisofendocytosisandadaptorrecruitmenttoshow thatm2,asubunitofAP2interactsdirectlywithphospholipaseD(PLD)1,areceptor-associatedsignalingproteinandthis facilitates the membrane recruitment of AP2 and the endocytosis of epidermal growth factor receptor (EGFR). We also demonstratethatthePLD1-m2interactionrequiresthebindingofPLD1withphosphatidicacid,itsownproduct. Conclusions/Significance: These results suggest that the temporal regulation of EGFR endocytosis is achieved by auto- regulatoryPLD1whichsensesthereceptoractivationandtriggersthetranslocationofAP2neartotheactivatedreceptor. Citation:LeeJS,KimIS,KimJH,ChoW,SuhP-G,etal.(2009)DeterminationofEGFREndocytosisKineticbyAuto-RegulatoryAssociationofPLD1withm2.PLoS ONE4(9):e7090.doi:10.1371/journal.pone.0007090 Editor:JamesKeen,ThomasJeffersonUniversity,KimmelCancerCenter,UnitedStatesofAmerica ReceivedNovember21,2008;AcceptedAugust18,2009;PublishedSeptember18,2009 Copyright:?2009Leeetal.Thisisanopen-accessarticledistributedunderthetermsoftheCreativeCommonsAttributionLicense,whichpermitsunrestricted use,distribution,andreproductioninanymedium,providedtheoriginalauthorandsourcearecredited. Funding:Thisworkwassuppo

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