Lipopolysaccharide(LPS)fromXXbacteriainducesawiderangeofinflammatoryresponses,includingtheresponseofalveolarmacrophagestobacteriainthelungs.CD14andtheToll-likereceptorTLR4areactivatedbyLPS,initiatingasignalingcascadethatactivatesPI3kinaseandincreasessynthesisoftheinositolphosphatePIP3(seeToll-likeReceptorpathway).PIP3activatestheinositolphosphatedependentproteinkinasePDK1,whichactivatesAKT(proteinkinaseB,seeAKTSignalingPathway).OneofthekeyactionsofAKTistoblockapoptosis.AKTphosphorylationofNF-kBpromotesthesurvivalandactivationofmacrophagesrespondingtoLPS.AnothersubstrateofAKTistheproteinkinaseGsk3-beta.AKTphosphorylatesanddeactivatesGsk3-beta.Non-phosphorylatedGsk3-betaisactiveandphosphorylatesbeta-catenin,leADIngtoitsdegradationintheubiquitindependentproteosomepathway(seeproteosomepathway).StimulationbyLPScausestheaccumulationofbeta-catenininthenucleusandtheactivationofgenesinconcertwiththetranscriptionfactorLEF1.Thispathwayisprobablynotrestrictedtoalveolarpathway,butleadstotheactivationofbeta-catenindependentgenesbyLPSinothercellsaswell.Otherpathwaysregulatethispathwayalso,suchasthemodulationofPI3kinaseactivitybyceramide,andtheinhibitionofGsk3-betaactivitybytheWnt/frizzled/disheveled(DSH)pathway.

Contributor:

REFERENCES:FangX.,etal.(2000)Phosphorylationandinactivationofglycogensynthasekinase3byproteinkinaseA.Proc.Natl.Acad.Sci.U.S.A.97(22),11960-5MonickM.M.,etal.(2001)Ceramideregulateslipopolysaccharide-inducedphosphatidylinositol3-kinaseandAktactivityinhumanalveolarmacrophages.JImmunol.167(10),5977-85MonickM.M.,etal.(2001)LipopolysaccharideactivatesAktinhumanalveolarmacrophagesresultinginnuclearaccumulationandtranscriptionalactivityofbeta-catenin.J.Immunol.166(7),4713-20SolomonKR,etal.HeterotrimericGproteinsphysicallyassocieatedwiththelipopolysaccharidereceptorCD14modulatebothinvivoandinvitroresponsestolipopolysacharide.JClinInvest1998Dec1;102(11):pp2019-2027WuL,StrasserA,Decisions,decisions:b-catenin-mediatedactivationofTCF-IandLef-IinfluencesthefateofdevelopingTcells.NatureImmunology2001:pp824-823

================  蚂蚁淘在线  ================

免责声明：本文仅代表作者个人观点，与本网无关。其创作性以及文中陈述文字和内容未经本站证实，对本文以及其中全部或者部分内容、文字的真实性、完整性、及时性本站不做任何保证或承诺，请读者仅作参考，并请自行核实相关内容

版权声明：未经蚂蚁淘在线授权不得转载、摘编或利用其他方式使用上述作品。已经经本网授权使用作品的，应该授权范围内使用，并注明“来源：蚂蚁淘在线”。违反上述声明者，本网将追究其相关法律责任。