LAB/NTAL/Lat2: a force to be reckoned with in all leukocytes?

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

关键词: LAT;    PLCγ;    Grb2;    PI3K;   

DOI  :  10.1189/jlb.0410221

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

LAB/NTAL/Lat2isatransmembraneadaptorproteincloselyrelatedtoLAT.Itisexpressedinvariousmyeloidandlymphoidcells,manyofwhichalsoexpressLAT.PhosphorylationofLABoccursfollowingengagementofvariousITAM‐andnon‐ITAM‐linkedreceptorsandcanplaypositiveandnegativerolesfollowingreceptorengagement.LATbindsPLCγdirectly,resultinginefficientCa2+fluxanddegranulation.However,LABdoesnotcontainaPLCγ‐bindingmotifandonlybindsPLCγindirectly,possiblyviaGrb2,therebyresultinginsuboptimalsignaling.AsLATcansignalmoreefficientlythanLAB,competitionbetweenthe2forspace/substratesinthelipidraftscanattenuatesignaling.ThiscompetitionmodelrequirescoexpressionofLAT;however,LABisrepressive,evenincellslackingsubstantialLATexpressionsuchasmacrophagesandmatureBcells.ThereportedinteractionbetweenLABandtheubiquitinE3‐ligasec‐Cblsuggests1possiblemechanismforLAT‐independentinhibitionbyLAB,butsuchamodelrequiresfurtherinvestigation.Giventhewide‐reachingexpressionpatternofLAB,LABhastheabilitytomodulatesignalinginvirtuallyeverytypeofleukocyte.Regardlessofitsultimatemodeofaction,thepotentregulatorycapabilityofLABprovesthisproteintobeacomplexadaptorthatwarrantscontinued,substantialscrutinybybiochemistsandimmunologistsalike...

【 授权许可】

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