Bacterial and Host Determinants of MAL Activation upon EPEC Infection The Roles of Tir, ABRA, and FLRT3 英文参考文献.docVIP

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Bacterial and Host Determinants of MAL Activation upon EPEC Infection The Roles of Tir, ABRA, and FLRT3 英文参考文献.doc

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Bacterial and Host Determinants of MAL Activation upon EPEC Infection The Roles of Tir, ABRA, and FLRT3 英文参考文献

BacterialandHostDeterminantsofMALActivationupon EPECInfection:TheRolesofTir,ABRA,andFLRT3 RobertJ.W.Heath1,2,JohnM.Leong3,Bala′zsVisegra′dy4,LauraM.Machesky4,RamnikJ.Xavier1,2,5* 1Center for Computational and Integrative Biology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States of America, 2GastrointestinalUnit,CenterforInflammatoryBowelDisease,MassachusettsGeneralHospital,HarvardMedicalSchool,Boston,Massachusetts,UnitedStatesofAmerica, 3Department of Molecular Genetics and Microbiology, UMass Medical School, Worcester, Massachusetts, United States of America, 4Beatson Institute for Cancer Research,GarscubeEstate,Bearsden,Glasgow,UnitedKingdom,5TheBroadInstituteofMITandHarvard,Cambridge,Massachusetts,UnitedStatesofAmerica Abstract Infection of host cells by pathogenic microbes triggers signal transduction pathways leading to a multitude of host cell responses including actin cytoskeletal re-arrangements and transcriptional programs. The diarrheagenic pathogens EnteropathogenicE.coli(EPEC)andtherelatedEnterohemorrhagicE.coli(EHEC)subvertthehost-cellactincytoskeletonto formattachingandeffacinglesionsonthesurfaceofintestinalepithelialcellsbyinjectingeffectorproteinsviaatypeIII secretionsystem.HereweuseaMALtranslocationassaytoestablishtheeffectofbacterialpathogensonhostcellsignaling totranscriptionfactor activation.MALis acofactor ofSerumresponse factor(SRF), atranscription factorwith important roles in the regulation of the actin cytoskeleton. We show that EPEC induces nuclear accumulation of MAL-GFP. The translocatedintiminreceptorisessentialforthisprocessandphosphorylationofTyrosineresidues454and474isimportant. UsinganexpressionscreenweidentifyFLRT3,C22orf28andTESK1asnovelactivatorsofSRF.Importantlywedemonstrate thatABRA(actin-bindingRho-activatingprotein,alsoknownasSTARS)isnecessaryforEPEC-inducednuclearaccumulation ofMALandthenovelSRFactivatorFLRT3,isacomponentofthispathway.WefurtherdemonstratethatABRAisimportant forst