清道夫受体介导的脂质蓄积的分子机制.ppt

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1、IntracellularAccumulationofLipidsviaScavengerReceptorsFormationoffoamcellAthersclerosisisachronicinflammatoryreactioncausedbymacrophagesandlymphocytesthatuptakethepathogenicitylipidsinvadingthevessel.SR-AandCD36aretheprincipalreceptorsresponsibleforfoam-cellformationMa

2、crophagecelltakesuplipidbySR-AStructureofSR-ASixdomainsThreetypesTrimericmoleculeFoamcellformationMφadhesionHostdefenseandinnateimmunityAdaptiveresponsesDisordersofthenervoussystemPhagocytosisofapoptoticcellsFunctionsofSR-AThecytoplasmicdomainisthekeypartofthereceptorm

3、ediatetheinternalizationofligandssuchasox-LDLparticipatetheregulationofcelladhesionandmigrationaccommodatetheexpressionandtransportofreceptorlink-coupledwithdownstreamofsignalingpathwayFunctionsofSR-Acytoplasmicdomain:Cytoplasmicdomain：Murine:MTKEMTENQRLCPHEREDADCSSESV

4、KFDARSMTASLPHSTKNGPSVQEKLKSFK(55)Rabbit:MAQWDSFTDQQEDTDSCSESVKFDARSNTALLPPNPKGPPLQEKLKSFK(50)Bovine:MAQWDDFPDQQEDTDSCTESVKFDARSVTALLPPHPKNGPTLQERMKSYK(50)Human:MEQWDHFHNQQEDTDSCSESVKFDARSMTALLPPNPKNSPSLQEKLKSFK(50)MSR-AAcLDLHSP90,HSP70,andGAPDHDirectlyInteractwiththeCy

5、toplasmicDomainofMSRNakamuraT.etal.BBRC,290,858-864(2002)FunctionalandpossiblephysicalassociationofscavengerreceptorwithcytoplasmictyrosinekinaseLyninmonocyticTHP-l-derivedMacrophagesMikiS.etal.FEBSLetters,399,241-244(1996)HSP90HSP70GAPDHLynLigandBindingtoMacrophageSca

6、vengerReceptor-AInducesUrokinase-typePlasminogenActivatorExpressionbyaProteinKinase-dependentSignalingPathwayHsien-YehHsuetal.JBiolChem,273,1240-1246(1998)MSR-AAcLDLFucoidanPTKPLC-γPKCuPAMSR-AFucoidanHsp90,pp60SrcRac1PAKJNKp38PI3KproIL-1IL-1LigandsofMacrophageScavenger

7、ReceptorInduceCytokineExpressionviaDifferentialModulationofProteinKinaseSignalingPathwaysHsuHY.etal.JBiolChem,276,28719-28730(2001)MSR-AAcLDLinternalization,adhesionGi/oRegulationofacetylatedlowdensitylipoproteinuptakeinmacrophagesbypertussistoxin-sensitiveGproteinsSte

8、wartCetal.JLipidRes,41,807-813(2000)ClassAscavengerreceptorsmediatecelladhesionviaactivationofGi/oandformationoffocal