eIF-4Fandp70S6kinaseplaycriticalrolesintranslationalregulation.eIF-4FisacomplexwhosefunctionsincludetherecognitionofthemRNA5"capstructure(eIF-4E),deliveryofanRNAhelicasetothe5"region(eIF-4A),bridgingofthemRNAandtheribosome(eIF-4G),andcircularizationofthemRNAviainteractionbetweeneIF-4Gandthepoly(A)bindingprotein(PABP).Severalstimuli,includinggrowthfactorsandcytokines,regulatetheeIF-4complexandp70S6kinasebyinitiatingaphosphorylationcascadeinvolvingthesequentialactivationofPI3-K,PDK1/2,Akt/PKB,andFRAP/mTORkinase.FRAP/mTOR,togetherwithanunidentifiedkinase,phosphorylates4E-BP,leADIngtoitsdissociationfromandactivationofeIF-4E.MNK1/2,activatedbyERKandp38MAPK,phosphorylatesandactivateseIF-4E.BothprocessescontributetotheassociationofeIF-4EandeIF-4GtoformtheactiveeIF-4Fcomplex,anecessarycomponentofthe48Sinitiationcomplex.PhosphorylationofribosomalproteinS6byp70S6kinasestimulatesthetranslationofmRNAswitha5"oligopyrimidinetractwhichtypicallyencodecomponentsoftheproteinsynthesis.

Contributor:CellSignalingTechnology

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