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1、ebiregulatesepidermalgrowthfactorreceptorsignalingpathwaysinDrosophila1,41,4113XinzhongDong,LeoTsuda,KentonH.Zavitz,MichaelLin,SonghuiLi,31,2,5RichardW.Carthew,andS.LawrenceZipursky12DepartmentofBiologicalChemistry,MolecularBiologyInstituteandHowardHughesMedicalInstit
2、ute,TheSchool3ofMedicine,UniversityofCalifornia,LosAngeles,California90095USA;DepartmentofBiologicalSciences,UniversityofPittsburgh,Pittsburgh,Pennsylvania15260USAebiregulatestheepidermalgrowthfactorreceptor(EGFR)signalingpathwayatmultiplestepsinDrosophiladevelopment.
3、MutationsinebiandEgfrleadtosimilarphenotypesandshowgeneticinteractions.However,ebidoesnotshowgeneticinteractionswithotherRTKs(e.g.,torso)orwithcomponentsofthecanonicalRas/MAPkinasepathway.ebiencodesanevolutionarilyconservedproteinwithauniqueaminoterminus,distantlyrela
4、tedtoF-boxsequences,andsixtandemlyarrangedcarboxy-terminalWD40repeats.Theexistenceofcloselyrelatedproteinsinyeast,plants,andhumanssuggeststhatebifunctionsinahighlyconservedbiochemicalpathway.Proteinswithrelatedstructuresregulateproteindegradation.Similarly,inthedevelo
5、pingeye,ebipromotesEGFR-dependentdown-regulationofTramtrack88,anantagonistofneuronaldevelopment.[KeyWords:ebi;EGFR;tramtrack88;Fbox;WD40repeats;proteindegradation]ReceivedJanuary13,1999;revisedversionacceptedFeburary22,1999.Epidermalgrowthfactorreceptors(EGFRs)haveace
6、n-quiredforthedevelopmentofR7only,EGFRisessentialtralroleinvertebrateandinvertebratedevelopment(forforthedevelopmentofmost,ifnotall,cells,includingreview,seevanderGeeretal.1994;Wassarmanetal.R7(forreview,seeFreeman1996a).ThisdualRTKre-1995;Freeman1998).Biochemicalstud
7、ieslargelyinquirementisintriguing.Constitutivelyactiveoverex-mammaliansystemsandgeneticstudiesinCaenorhab-pressedformsofbothSevandEGFRaresufficienttoditiselegansandDrosophilahaveledtoadetailedde-induceR7development.Furthermore,overexpressionofscriptionofthesignaltrans
8、ductionpathwayselicitedbySpitz,aligandforEGFR,canpartiallyrescueR7devel-activationoftheEGFR(forreview,seeKayneandStern-opmen
