Phosphorylation of eIF2α triggered by mTORC1 inhibition and PP6C activation is required for autophagy and is aberrant in PP6C-mutated melanoma
Wengrod J, Wang D, Weiss S, Zhong H, Osman I, Gardner LB. Phosphorylation of eIF2α triggered by mTORC1 inhibition and PP6C activation is required for autophagy and is aberrant in PP6C-mutated melanoma. Science Signaling 2015, 8: ra27. PMID: 25759478, PMCID: PMC4580977, DOI: 10.1126/scisignal.aaa0899.Peer-Reviewed Original ResearchMeSH KeywordsAmino AcidsAutophagyCell Line, TumorClustered Regularly Interspaced Short Palindromic RepeatsEnzyme ActivationEukaryotic Initiation Factor-2Gene Knock-In TechniquesHumansImmunoblottingImmunohistochemistryImmunoprecipitationMass SpectrometryMechanistic Target of Rapamycin Complex 1MelanomaMicroscopy, FluorescenceMultiprotein ComplexesMutationPhosphoprotein PhosphatasesPhosphorylationProtein Serine-Threonine KinasesSirolimusTOR Serine-Threonine KinasesTunicamycinConceptsKinase complex mTORC1Amino acid-sensing systemsProtein phosphatase 6Activation of GCN2Amino acid deprivationEukaryotic initiation factorPharmacological inhibitionWild-type alleleKinase GCN2Human melanoma samplesGCN2 activationRegulatory subunitCatalytic subunitInitiation factorsPathways downstreamPP6cGCN2MTORC1PhosphorylationAutophagyMutantsMelanoma samplesSubunitsMutationsActivation