SnapShot:mTORSignalingAlexandreSoulardandMichaelN.HallBiozentrum,UniversityofBasel,CH-4056Basel,Switzerland434Cell129,April20,2007©2007ElsevierInc.DOI10.1016/j.cell.2007.04.010Seeonlineversionforlegendandreferences.mTOR(mammalianTargetofRapamycin)integratesthreemajorinputs—nutrients(aminoacids),growthfactors(insulin),andcellularenergystatus—tocontrolseveralcatabolicandanabolicprocessesthatcollectivelydeterminecellgrowthandmetabolism.mTORformstwostructurallyandfunctionallydistinctmultiproteincomplex-es,mTORC1andmTORC2,whichcorrespondtotwomajorbrancheswithintheoverallsignalingnetwork.BothmTORC1andmTORC2areatypicalserine/threoninekinases.ThemaincomponentsofthenetworkotherthanthemTORCsaredepictedinbrightyellow.Inresponsetogrowthfactors,AKTphosphorylatesandinactivatesTSC1-TSC2(aheterodimericGTPase-activatingprotein),allowingGTP-boundRheb(aRas-likeGTPase)toactivatemTORC1andpossiblymTORC2.Lowenergy(cel-lularenergystatus)inhibitsmTORCbyactivatingAMPK,whichphosphorylatesandactivatesTSC1-TSC2.Thepathwaybywhichaminoacids,leucineinparticular,activatemTORC1ispoorlyunderstood.mTORC1controlsproteinsynthesisbyphosphorylatingandinactivatingthetranslationalinhibitor4E-BPandbyphosphorylat-ingandactivatingS6kinase(S6K).S6K,inadditiontophosphorylatingvarioustranslationaltargets,alsophosphorylatesandinhibitsinsulinreceptorsubstrate1(IRS-1)aspartofanegativefeedbackloopthatattenuatesinsulinsignaling.mTORC2promotescellsurvivalthroughdirectphosphorylationofserine473inthehydrophobicmotifofAKT.TheimmunosuppressantrapamycinincomplexwithFKBPbindsandinhibitsmTORC1butnotmTORC2.mTORsignalingisderegulatedinmanydiseasesincludingcancerandmetabolicdisorders.mTORalsomediatesnutrient-relatedprocessessuchasappetitecontrolandaging.RefeRencesAvruch,J.,Hara,K.,Lin,Y.,Liu,M.,Long,X.,Ortiz-Vega,S.,andYonezawa,K.(2006).Insulinandamino-acidregulationofmTORsignalingandkinaseactivitythroughtheRhebGTPase.Oncogene25,6361–6372.Corradetti,M.N.,andGuan,K.L.(2006).Upstreamofthemammaliantargetofrapamycin:doallroad...
