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.

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