Manycell-surfacereceptorsinduceproductionofsecondmessengerslikePIP3,phosphatidylinositol3,4,5-trisphosphate,thatconveysignalstothecytoplasmfromthecellsurface.PIP3signalsactivatesthekinasePDK1,3-phosphoinositide-dependentproteinkinase-1,whichinturnactivatesthekinaseAKT,alsoknownasproteinkinaseB.ProteinsphosphorylatedbyactivatedAKTpromotecellsurvival.PhosphorylationofIkappa-BkinaseleadstoactivationofthetranscriptionfactorNF-kBtoopposeapoptosis.BadisaproteinintheBcl-2genefamilythatopposesBcl-2toinduceapoptosis.PhosphorylationofBadbyAKTblocksanti-apoptoticactivitytopromotecellsurvival.Similarly,phosphorylationoftheproteasecaspase9orforkheadtranscriptionfactorsbyAKTblocktheinductionofapoptosisbythesefactors.AKTpromotescellsurvivalandopposesapoptosisbyavarietyofroutes. Contributor:GlennCroston,PhD. REFERENCES: