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1、CellularSignalling24(2012)1810–1820ContentslistsavailableatSciVerseScienceDirectCellularSignallingjournalhomepage:www.elsevier.com/locate/cellsigReviewRegulationofVEGFsignalingbymembranetraffica,b,⁎,HimabinduReddySeerapuaArieHorowitzaDepartmentofMolecularCardi
2、ology,LernerResearchInstitute,ClevelandClinicLernerCollegeofMedicine,9500EuclidAvenue,Cleveland,OH44195,USAbDepartmentofPhysiologyandBiophysics,CaseWesternReserveUniversitySchoolofMedicine,10900EuclidAvenue,Cleveland,OH44106,USAarticleinfoabstractArticlehisto
3、ry:RecentfindingshavedrawnattentiontotheroleofmembranetrafficinthesignalingofvascularendothelialReceived23April2012growthfactor(VEGF).ThesignificanceofthisdevelopmentstemsfromthepivotalfunctionofVEGFinAccepted9May2012vasculogenesisandangiogenesis.Theoutlineofthe
4、regulationofVEGFreceptor(VEGFR)signalingbymem-Availableonline19May2012branetrafficissimilartothatoftheepidermalgrowthfactorreceptor(EGFR),aprototypeoftheintertwiningbetweenmembranetrafficandsignaling.Thereare,however,uniquefeaturesinVEGFRsignalingthatareKeyword
5、s:conferredinpartbytheinvolvementoftheco-receptorneuropilin(Nrp).Nrp1andVEGFR2areintegratedAngiogenesisEndocytosisintomembranetrafficthroughtheadaptorproteinsynectin,whichrecruitsmyosinVI,amolecularmotorMembranetrafficthatdrivesinwardtrafficking[17,21,64].Therec
6、entdetectionofonlymildvasculardefectsinaknockinNeuropilin-1mousemodelthatexpressesNrp1lackingacytoplasmicdomain[104],questionstheco-receptor'sroleinRhoGTPaseVEGFsignalingandmembranetraffic.Theregulationofendocytosisbyephrin-B2isanotherfeatureuniqueVEGFR2toVEGR
7、2/3[18,19],butitawaitsamechanisticexplanation.Currentmodelsdonotfullyexplainhowmem-branetrafficbridgesbetweenVEGFRandthedownstreameffectorsthatproduceitsfunctionaloutcome,suchascellmigration.VEGF-Aappearstoaccomplishthistaskinpartbyrecruitingendocyticvesiclesc
8、arryingRhoAtointernalizedactiveVEGFR2[58].©2012ElsevierInc.Allrightsreserved.Contents1.Introduction.............................................................18111.1.Overview:regulation
