Seeonlineversionforlegend,abbreviations,andreferences.1024Cell129,June1,2007©2007ElsevierInc.DOI10.1016/j.cell.2007.05.017SnapShot:Pattern-RecognitionReceptorsTaroKawaiandShizuoAkiraResearchInstituteforMicrobialDiseases,OsakaUniversity,Osaka,JapanSnapShot:Pattern-RecognitionReceptorsTaroKawaiandShizuoAkiraResearchInstituteforMicrobialDiseases,OsakaUniversity,Osaka,Japan1024.e1Cell129,June1,2007©2007ElsevierInc.DOI10.1016/j.cell.2007.05.017(A)Toll-likereceptorsignaling.Toll-likereceptor(TLR)3recognizespolyinosinic-polycytidylicacid(polyIC),whereasTLR4recognizeslipopolysaccharide(LPS).TLR2recog-nizesvariouscomponentssuchaslipoproteinandpeptidoglycan(PGN).TLR5detectsflagellin.TLR7andTLR9detectsingle-stranded(ss)RNAandCpGDNA,respectively.EachTLRrecruitsadistinctsetofToll/interleukin-1receptor(TIR)domain-containingadaptormoleculessuchasmyeloiddifferentiationprimaryresponsegene88(MyD88),TIR-containingadaptorprotein(TIRAP,alsoknownasMAL),TIR-containingadaptor-inducingIFNβ(TRIF,alsoknownasTICAM1)andTRIF-relatedadaptormolecule(TRAM,alsoknownasTICAM2).TLR3usesTRIF,andTLR5,7,and9useMyD88.TLR2usesMyD88andTIRAP,andTLR4usesMyD88,TIRAP,TRIF,andTRAM.MyD88bindstointer-leukin-1receptor-associatedkinase4(IRAK4)andTRAF6.TRIFbindsreceptor-interactingprotein1(RIP1)andTRAF6.TRAF6formsacomplexwithUbc13,Uev1A,andECSIT(evolutionarilyconservedsignalingintermediateinToll/IL-1Rpathways)toactivateacomplexcontainingtransforminggrowthfactor-β-activatedkinase1(TAK1),TAK1-bindingprotein1(TAB1),TAB2,andTAB3.TAK1activatesIκBkinase(IKK)complexconsistingofIKKα,IKKβ,andNemo(alsoknownasIKKγ),whichresultsinthephosphorylationandproteasomaldegradationofIκBproteinsandthereleaseofatranscriptionfactorNFκBtothenucleustoregulateexpressionofinflammatorycytokinessuchasinterleukin-6(IL-6)andtumornecrosisfactorα(TNFα).TAK1simultaneouslyactivatestheMAPK(JNK,p38,andERK)pathway,leadingtoactivationofAP-1thatcontrolsexpressionofinflammatorycytokines.TRIFrecruitsTRAF3,whichinteractswithIKK-relatedkinases,TAN...
