期刊论文详细信息
Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society | |
Regulation of Class A scavenger receptor‐mediated cell adhesion and surface localization by PI3K: identification of a regulatory cytoplasmic motif | |
关键词: macrophage; signal transduction; inflammation; structure‐; function; | |
DOI : 10.1189/jlb.0509318 | |
学科分类:生理学 | |
来源: Federation of American Societies for Experimental Biology | |
【 摘 要 】
TheimportanceofcytoplasmicmotifsindifferentiallyregulatingSR‐Afunctionwasdemonstratedbydeletingthefirst49cytoplasmicaa(SR‐AΔ1–49),whichabolishedSR‐A‐mediatedligandinternalizationwithoutreducingcelladhesion.Toidentifyadditionalcytoplasmicmotifswithinthefirst49aathatregulateSR‐Afunction,theacidicresiduesinaconservedmotif(EDAD)werechangedtotheiramidederivatives(SR‐AQNAN).ThefunctionandregulationofSR‐AQNANwerecomparedwiththatofSR‐AΔ1–49andSR‐AintransfectedHEK‐293cells.BlockingPI3KactivationinhibitedSR‐A,butnotSR‐AΔ1–49‐orSR‐AQNAN‐mediatedcelladhesion.Althoughdeleting(SR‐AΔ1–49)ormutating(SR‐AQNAN)theEDADmotifabolishedthePI3KsensitivityofSR‐A‐mediatedcelladhesion,thesemutationsdidnotaffectligandinternalizationorPI3Kactivationduringcelladhesion.TodefinethemechanismbywhichPI3KregulatesSR‐A‐mediatedcelladhesion,thecellularlocalizationofwild‐typeandmutantSR‐Awasexamined.PI3KinhibitionreducedsurfacelocalizationofSR‐AbutnotofSR‐AΔ1–49orSR‐AQNAN.TheregulationofSR‐AsurfacelocalizationbyPI3Kwasconfirmedinperitonealmacrophages,whichendogenouslyexpressSR‐A.Together,theseresultssuggestapathwayinwhichSR‐AbindingtoanimmobilizedligandactivatesPI3Ktorecruitmorereceptortotheplasmamembraneandenhancescelladhesion...【 授权许可】
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