清道夫受体介导的脂质蓄积的分子机制PPT课件.ppt

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1、IntracellularAccumulationofLipidsviaScavengerReceptorsQiChenNanjingMedicalUniversity2005.8FormationoffoamcellAthersclerosisisachronicinflammatoryreactioncausedbymacrophagesandlymphocytesthatuptakethepathogenicitylipidsinvadingthevessel.SR-AandCD36are

2、theprincipalreceptorsresponsibleforfoam-cellformationMacrophagecelltakesuplipidbySR-AStructureofSR-ASixdomainsThreetypesTrimericmoleculeFoamcellformationMφadhesionHostdefenseandinnateimmunityAdaptiveresponsesDisordersofthenervoussystemPhagocytosisofa

3、poptoticcellsFunctionsofSR-AThecytoplasmicdomainisthekeypartofthereceptormediatetheinternalizationofligandssuchasox-LDLparticipatetheregulationofcelladhesionandmigrationaccommodatetheexpressionandtransportofreceptorlink-coupledwithdownstreamofsignali

4、ngpathwayFunctionsofSR-Acytoplasmicdomain:Cytoplasmicdomain：Murine:MTKEMTENQRLCPHEREDADCSSESVKFDARSMTASLPHSTKNGPSVQEKLKSFK(55)Rabbit:MAQWDSFTDQQEDTDSCSESVKFDARSNTALLPPNPKGPPLQEKLKSFK(50)Bovine:MAQWDDFPDQQEDTDSCTESVKFDARSVTALLPPHPKNGPTLQERMKSYK(50)Hum

5、an:MEQWDHFHNQQEDTDSCSESVKFDARSMTALLPPNPKNSPSLQEKLKSFK(50)MSR-AAcLDLHSP90,HSP70,andGAPDHDirectlyInteractwiththeCytoplasmicDomainofMSRNakamuraT.etal.BBRC,290,858-864(2002)Functionalandpossiblephysicalassociationofscavengerreceptorwithcytoplasmictyrosin

6、ekinaseLyninmonocyticTHP-l-derivedMacrophagesMikiS.etal.FEBSLetters,399,241-244(1996)HSP90HSP70GAPDHLynLigandBindingtoMacrophageScavengerReceptor-AInducesUrokinase-typePlasminogenActivatorExpressionbyaProteinKinase-dependentSignalingPathwayHsien-YehH

7、suetal.JBiolChem,273,1240-1246(1998)MSR-AAcLDLFucoidanPTKPLC-γPKCuPAMSR-AFucoidanHsp90,pp60SrcRac1PAKJNKp38PI3KproIL-1IL-1LigandsofMacrophageScavengerReceptorInduceCytokineExpressionviaDifferentialModulationofProteinKinaseSignalingPathwaysHsuHY.etal.

8、JBiolChem,276,28719-28730(2001)MSR-AAcLDLinternalization,adhesionGi/oRegulationofacetylatedlowdensitylipoproteinuptakeinmacrophagesbypertussistoxin-sensitiveGproteinsStewartCetal.JLipidRes,41,807-813(2000)ClassAscavengerreceptorsmediatecelladhesionvi