分子医学-炎症、感染与相关疾病.ppt

分子医学-炎症、感染与相关疾病.ppt

  1. 1、本文档共81页,可阅读全部内容。
  2. 2、原创力文档(book118)网站文档一经付费(服务费),不意味着购买了该文档的版权,仅供个人/单位学习、研究之用,不得用于商业用途,未经授权,严禁复制、发行、汇编、翻译或者网络传播等,侵权必究。
  3. 3、本站所有内容均由合作方或网友上传,本站不对文档的完整性、权威性及其观点立场正确性做任何保证或承诺!文档内容仅供研究参考,付费前请自行鉴别。如您付费,意味着您自己接受本站规则且自行承担风险,本站不退款、不进行额外附加服务;查看《如何避免下载的几个坑》。如果您已付费下载过本站文档,您可以点击 这里二次下载
  4. 4、如文档侵犯商业秘密、侵犯著作权、侵犯人身权等,请点击“版权申诉”(推荐),也可以打举报电话:400-050-0827(电话支持时间:9:00-18:30)。
查看更多

MyD88knockoutmicehavenoresponsetoLPSMyD88isessentialtoallinflammatorysignalingpathwaysMyD88s,asplicevariantofMyD88downregulatestheinflammatoryresponseMyD88interactswithTIRdomainofTLRandrecruitsIRAK-4,IRAK-1andTRAF-6MyD88AdaptorRakoff-Nahoumetal.,RecognitionofcommensalmicroflorabyToll-likereceptorsisrequiredforintestinalhomestasis.Cell118:229-41,2004.*4IRAKsknown,IRAK1,IRAK-2,IRAK-MandIRAK-4IRAKareserine/threoninekinasesIRAK-4phosphorylatesIRAK-1IRAK-MplaysaninhibitoryroleinTLRsignalingTRAF6isamemberoftheTNFreceptorassociatedfactor(TRAF)familyTRAF6interactswithIRAK-1andgetsactivatedReleaseofTRAF6/IRAK-1ensuessubsequentsignalingIRAKandTRAF6IL-1RI-associatedproteinkinases(IRAKs)tumornecrosisfactorreceptor-associatedfactor6(TRAF6).*TRAF6/IRAK-1complexassociateswith3proteinsTAK1(TGF-Bactivatedkinase)TAB1(TAK1bindingproteins)TAB2(TAK1bindingproteins)LargecomplexassociateswithmembraneEventuallyIRAK-1staysinmembranewhileTRAF6/TAK1/TAB1/TAB2movetocytosolE2LigasessuchasUbc13andUev1AjoinfurtherenlargingcomplexIRAKandTRAF6Release*TAK-1ActivationTheenlargedcomplexthatincludesTRAF6,TAK1,TAB1,TAB2,Ubc13,Uev1AactivateTAK1ActivatedTAK1phosphorylatesIKKcomplexActivatedTAK1canalsophosphorylateMAPKinasesIKKcomplexconsistsofIKK?,?and?/NEMOI?BphosphorylationresultsinNF-?Btranslocationtonucleus*OverviewofMyD88-dependentpathway*MyD88IndependentPathwayMyD88KnockoutmicedonotproduceinflammatorycytokinessuchasTNF-?HoweverwithTLR4stimulationNF-?BandJNKdelayedactivityoccursThisstronglysuggeststheexistenceof2pathwaysinTLRsignalingaMyD88dependentpathwayaMyD88independentpathwayTLR3stimulationalsoexchibitsaMyD88independentpathwayTLR4*OverviewofTLRsignaling**InflammationCytokinesChemokinesF

文档评论(0)

一壶清茶 + 关注
实名认证
内容提供者

该用户很懒,什么也没介绍

1亿VIP精品文档

相关文档