2016
Serine 302 Phosphorylation of Mouse Insulin Receptor Substrate 1 (IRS1) Is Dispensable for Normal Insulin Signaling and Feedback Regulation by Hepatic S6 Kinase*
Copps K, Hançer N, Qiu W, White M. Serine 302 Phosphorylation of Mouse Insulin Receptor Substrate 1 (IRS1) Is Dispensable for Normal Insulin Signaling and Feedback Regulation by Hepatic S6 Kinase*. Journal Of Biological Chemistry 2016, 291: 8602-8617. PMID: 26846849, PMCID: PMC4861431, DOI: 10.1074/jbc.m116.714915.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SubstitutionAnimalsCHO CellsCricetinaeCricetulusGene DeletionGlucose IntoleranceInsulinInsulin Receptor Substrate ProteinsLiverMechanistic Target of Rapamycin Complex 1MiceMice, TransgenicMultiprotein ComplexesMutation, MissensePhosphatidylinositol 3-KinasesPhosphorylationProto-Oncogene Proteins c-aktRibosomal Protein S6 KinasesSerineSignal TransductionTOR Serine-Threonine KinasesTuberous Sclerosis Complex 1 ProteinTumor Suppressor ProteinsConceptsInsulin receptor substrate-1Receptor substrate-1PI3K associationS6 kinaseSubstrate-1Insulin-stimulated Akt activityAkt phosphorylationK associationRapamycin complex 1S6K signalingInsulin-stimulated IRS1 tyrosine phosphorylationSer-302IRS1 tyrosine phosphorylationMTORC1 inhibitor rapamycinRibosomal S6 proteinTsc1 deletionFeedback phosphorylationIntracellular amino acidsInsulin sensitivityTyrosine phosphorylationAlanine mutationsS6 proteinS6KAkt activityInsulin signaling
2014
Insulin and Metabolic Stress Stimulate Multisite Serine/Threonine Phosphorylation of Insulin Receptor Substrate 1 and Inhibit Tyrosine Phosphorylation*
Hançer N, Qiu W, Cherella C, Li Y, Copps K, White M. Insulin and Metabolic Stress Stimulate Multisite Serine/Threonine Phosphorylation of Insulin Receptor Substrate 1 and Inhibit Tyrosine Phosphorylation*. Journal Of Biological Chemistry 2014, 289: 12467-12484. PMID: 24652289, PMCID: PMC4007441, DOI: 10.1074/jbc.m114.554162.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnisomycinAntigens, CDBlotting, WesternCHO CellsCricetinaeCricetulusEnzyme InhibitorsHumansHypoglycemic AgentsInsulinInsulin Receptor Substrate ProteinsPhosphatidylinositol 3-KinasesPhosphoinositide-3 Kinase InhibitorsPhosphorylationProtein Serine-Threonine KinasesProto-Oncogene Proteins c-aktRatsReceptor, InsulinRibosomal Protein S6 Kinases, 70-kDaSerineSignal TransductionThapsigarginThreonineTOR Serine-Threonine KinasesTunicamycinTyrosineConceptsTyrosine phosphorylationPhospho-specific monoclonal antibodiesSerine/threonine phosphorylationInsulin receptor tyrosine kinasePI3KInsulin receptor substrate-1Insulin-stimulated cellsHuman insulin receptorIRS1 tyrosine phosphorylationReceptor substrate-1Metabolic stressReceptor tyrosine kinasesThreonine phosphorylationThreonine residuesS6 kinasePI3K inhibitionSubstrate-1Mechanistic targetTyrosine kinaseInsulin stimulationMEK pathwayKey substrateInsulin receptorPresence of inhibitorsCHO cells
2008
Structural and biochemical characterization of the KRLB region in insulin receptor substrate-2
Wu J, Tseng Y, Xu C, Neubert T, White M, Hubbard S. Structural and biochemical characterization of the KRLB region in insulin receptor substrate-2. Nature Structural & Molecular Biology 2008, 15: 251-258. PMID: 18278056, DOI: 10.1038/nsmb.1388.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsCHO CellsCricetinaeCricetulusCrystallography, X-RayHumansInsulin Receptor Substrate ProteinsIntracellular Signaling Peptides and ProteinsMiceModels, MolecularMolecular Sequence DataMutationPhosphoproteinsPhosphorylationPhosphotyrosineProtein BindingProtein Structure, TertiaryProtein-Tyrosine KinasesReceptor, IGF Type 1Structure-Activity RelationshipSubstrate SpecificityConceptsInsulin receptorPleckstrin homology domainCrucial adaptor proteinTwo-hybrid studiesInsulin receptor kinaseKinase active siteInsulin receptor substrate 2C-terminal regionTyrosine kinase domainPrevious yeastThreonine phosphorylationHomology domainAdaptor proteinReceptor kinaseKinase domainTyrosine phosphorylationBiochemical characterizationRegion functionsSubstrate 2Binding regionsPhosphorylationKinase inhibitionFactor 1IRS2Insulin-like growth factor-1
2007
Phosphorylation of Irs1 at SER-522 Inhibits Insulin Signaling
Giraud J, Haas M, Feener E, Copps K, Dong X, Dunn S, White M. Phosphorylation of Irs1 at SER-522 Inhibits Insulin Signaling. Endocrinology 2007, 21: 2294-2302. PMID: 17579213, DOI: 10.1210/me.2007-0159.Peer-Reviewed Original ResearchConceptsTyrosine phosphorylationInsulin-stimulated tyrosine phosphorylationInsulin-stimulated IRS1 tyrosine phosphorylationIRS1 tyrosine phosphorylationInsulin-stimulated phosphorylationPhosphorylation of IRS1Threonine residuesMultisite phosphorylationPhosphorylation sitesPhosphoserine antibodyInhibits InsulinL6 myoblastsPhosphorylationCultured cellsIRS1Akt expressionPhosphatidylinositolFunctional effectsMass spectrometryPD98059WortmanninMyoblastsMyotubesRNASerine
2003
Nutrient-dependent and Insulin-stimulated Phosphorylation of Insulin Receptor Substrate-1 on Serine 302 Correlates with Increased Insulin Signaling*
Giraud J, Leshan R, Lee Y, White M. Nutrient-dependent and Insulin-stimulated Phosphorylation of Insulin Receptor Substrate-1 on Serine 302 Correlates with Increased Insulin Signaling*. Journal Of Biological Chemistry 2003, 279: 3447-3454. PMID: 14623899, DOI: 10.1074/jbc.m308631200.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAmino AcidsAndrostadienesAnimalsBlotting, WesternBromodeoxyuridineCell DivisionCell LineCHO CellsCricetinaeCulture Media, Serum-FreeDose-Response Relationship, DrugEnzyme InhibitorsGlucoseGlycogen Synthase Kinase 3Glycogen Synthase Kinase 3 betaInsulinInsulin Receptor Substrate ProteinsJNK Mitogen-Activated Protein KinasesMiceMitogen-Activated Protein KinasesMolecular Sequence DataMutagenesis, Site-DirectedMutationPhosphoproteinsPhosphorylationPoint MutationPrecipitin TestsRatsSerineSignal TransductionSirolimusTime FactorsWortmanninConceptsInsulin/IGFIRS-1Insulin-stimulated signal transductionInsulin receptor substrate IRS-1Ser/Thr phosphorylationSequence-specific polyclonal antibodiesInsulin-stimulated tyrosine phosphorylationInsulin receptor substrate-1Synthase kinase-3beta phosphorylationSubstrate IRS-1IRS-1-mediated signalingRibosomal S6 proteinC-Jun kinaseInsulin-stimulated phosphorylationReceptor substrate-1IGF-I stimulationThr phosphorylationKinase associatesP85 bindingPhosphorylated residuesSignal transductionInsulin-stimulated AktTyrosine phosphorylationS6 proteinNutrient availability
2001
Insulin/IGF-1 and TNF-α stimulate phosphorylation of IRS-1 at inhibitory Ser307 via distinct pathways
Rui L, Aguirre V, Kim J, Shulman G, Lee A, Corbould A, Dunaif A, White M. Insulin/IGF-1 and TNF-α stimulate phosphorylation of IRS-1 at inhibitory Ser307 via distinct pathways. Journal Of Clinical Investigation 2001, 107: 181-189. PMID: 11160134, PMCID: PMC199174, DOI: 10.1172/jci10934.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnisomycinCHO CellsCricetinaeInsulinInsulin AntagonistsInsulin ResistanceInsulin-Like Growth Factor IMAP Kinase Kinase 1Mitogen-Activated Protein Kinase KinasesPhosphatidylinositol 3-KinasesPhosphorylationProtein Serine-Threonine KinasesReceptor, InsulinSerineSignal TransductionTumor Necrosis Factor-alphaTyrosineConceptsPhosphorylation of Ser307IRS-1Serine/threonine phosphorylationTNF-alpha-stimulated phosphorylationInsulin-stimulated tyrosine phosphorylationRelevant phosphorylation sitesDistinct kinase pathwaysInsulin/IGFInsulin-stimulated phosphorylationThreonine phosphorylationStimulates PhosphorylationPhosphorylation sitesJun kinaseTyrosine phosphorylationKinase pathwaySer307PhosphorylationCultured cellsDistinct pathwaysHeterologous inhibitionPolyclonal antibodiesPreadipocytesPathwayAdipocytesCells
2000
The c-Jun NH2-terminal Kinase Promotes Insulin Resistance during Association with Insulin Receptor Substrate-1 and Phosphorylation of Ser307 *
Davis R, Aguirre V, Uchida T, Yenush L, White M. The c-Jun NH2-terminal Kinase Promotes Insulin Resistance during Association with Insulin Receptor Substrate-1 and Phosphorylation of Ser307 *. Journal Of Biological Chemistry 2000, 275: 9047-9054. PMID: 10722755, DOI: 10.1074/jbc.275.12.9047.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsAnisomycinCHO CellsCricetinaeHumansInsulinInsulin Receptor Substrate ProteinsInsulin ResistanceJNK Mitogen-Activated Protein KinasesMiceMitogen-Activated Protein KinasesMolecular Sequence DataPhosphoproteinsPhosphorylationProtein BindingReceptor, InsulinRecombinant ProteinsSerineSignal TransductionTumor Necrosis Factor-alphaConceptsInsulin-stimulated tyrosine phosphorylationIRS-1Serine 307Tyrosine phosphorylationInsulin receptor substrate-1IRS-1 functionSignal transduction cascadePhosphorylation of Ser307Receptor substrate-1Chinese hamster ovary cellsIRS proteinsActivity of JNKJNK associatesPhosphorylation sitesHamster ovary cellsTransduction cascadeSerine phosphorylationTerminal kinaseSubstrate-1PhosphorylationStrong activatorPromotes Insulin ResistanceJNK phosphorylationOvary cellsJNK
1998
The COOH-terminal Tyrosine Phosphorylation Sites on IRS-1 Bind SHP-2 and Negatively Regulate Insulin Signaling*
Myers M, Mendez R, Shi P, Pierce J, Rhoads R, White M. The COOH-terminal Tyrosine Phosphorylation Sites on IRS-1 Bind SHP-2 and Negatively Regulate Insulin Signaling*. Journal Of Biological Chemistry 1998, 273: 26908-26914. PMID: 9756938, DOI: 10.1074/jbc.273.41.26908.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCalcium-Calmodulin-Dependent Protein KinasesCell DivisionCHO CellsCricetinaeEnzyme ActivationHumansInsulinInsulin Receptor Substrate ProteinsIntracellular Signaling Peptides and ProteinsPhosphatidylinositol 3-KinasesPhosphoproteinsPhosphorylationProtein BindingProtein Tyrosine Phosphatase, Non-Receptor Type 11Protein Tyrosine Phosphatase, Non-Receptor Type 6Protein Tyrosine PhosphatasesRatsSignal TransductionTyrosineConceptsSHP-2Tyrosine phosphorylationIRS-1Terminal tyrosine phosphorylation sitesTyrosine-phosphorylated motifsTyrosine phosphorylation sitesImportant regulatory eventInsulin receptor substrateProtein kinase activationSH2 domainGrb-2Phosphorylation sitesDownstream signal transmissionNumerous growth factorsRegulatory eventsReceptor substrateKinase activationInsulin signalingTyrosine kinaseInsulin stimulationCytokine receptorsProtein synthesisPhosphorylationTerminal tyrosineDownstream signals
1996
Growth Hormone, Interferon-γ, and Leukemia Inhibitory Factor Utilize Insulin Receptor Substrate-2 in Intracellular Signaling*
Argetsinger L, Norstedt G, Billestrup N, White M, Carter-Su C. Growth Hormone, Interferon-γ, and Leukemia Inhibitory Factor Utilize Insulin Receptor Substrate-2 in Intracellular Signaling*. Journal Of Biological Chemistry 1996, 271: 29415-29421. PMID: 8910607, DOI: 10.1074/jbc.271.46.29415.Peer-Reviewed Original ResearchMeSH Keywords3T3 CellsAnimalsCHO CellsCricetinaeGrowth InhibitorsHuman Growth HormoneHumansInsulin Receptor Substrate ProteinsInterferon-gammaInterleukin-6Intracellular Signaling Peptides and ProteinsLeukemia Inhibitory FactorLymphokinesMicePhosphatidylinositol 3-KinasesPhosphoproteinsPhosphorylationPhosphotransferases (Alcohol Group Acceptor)Signal TransductionTyrosineConceptsInsulin receptor substrate 2Tyrosyl phosphorylationLeukemia inhibitory factorProtein tyrosine phosphatase SHP2Substrate 2JAK2 associationPhosphatase SHP2Regulatory subunitJAK kinasesMaximal phosphorylationTyrosine phosphorylationTyrosine residuesIntracellular signalingPhosphorylationMultiple membersGH receptorInhibitory factorCytokine familyGrowth hormoneReceptorsSHP2KinasePhosphatidylinositolSubstantial signalInsulin-induced egr-1 and c-fos Expression in 32D Cells Requires Insulin Receptor, Shc, and Mitogen-activated Protein Kinase, but Not Insulin Receptor Substrate-1 and Phosphatidylinositol 3-Kinase Activation*
Harada S, Smith R, Smith J, White M, Jarett L. Insulin-induced egr-1 and c-fos Expression in 32D Cells Requires Insulin Receptor, Shc, and Mitogen-activated Protein Kinase, but Not Insulin Receptor Substrate-1 and Phosphatidylinositol 3-Kinase Activation*. Journal Of Biological Chemistry 1996, 271: 30222-30226. PMID: 8939974, DOI: 10.1074/jbc.271.47.30222.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAnimalsCell LineCHO CellsCricetinaeDNA-Binding ProteinsEarly Growth Response Protein 1Enzyme ActivationEnzyme InhibitorsGene Expression RegulationGRB2 Adaptor ProteinImmediate-Early ProteinsInsulinInsulin Receptor Substrate ProteinsMicePhosphatidylinositol 3-KinasesPhosphoproteinsPhosphorylationPhosphotransferases (Alcohol Group Acceptor)Protein KinasesProteinsProto-Oncogene Proteins c-fosReceptor, InsulinRNA, MessengerTranscription FactorsTyrosineConceptsC-fos expressionInsulin receptor substrate-1Egr-1 expressionInsulin receptorReceptor substrate-1Mitogen-activated protein kinase activationEgr-1Protein kinase activationMultiple signal transduction pathwaysBlot analysisEffect of insulinSignal transduction pathwaysSubstrate-1Tyrosine phosphorylationImmediate early gene Egr-1Mitogen-activated protein kinase kinase inhibitorWestern blot analysisProtein kinase kinase inhibitorInsulin receptor tyrosine phosphorylationInsulin treatmentKinase activationIRS-1 phosphorylationTransduction pathwaysKinase kinase inhibitorGene Egr-1The Fyn Tyrosine Kinase Binds Irs-1 and Forms a Distinct Signaling Complex during Insulin Stimulation (∗)
Sun X, Pons S, Asano T, Myers M, Glasheen E, White M. The Fyn Tyrosine Kinase Binds Irs-1 and Forms a Distinct Signaling Complex during Insulin Stimulation (∗). Journal Of Biological Chemistry 1996, 271: 10583-10587. PMID: 8631859, DOI: 10.1074/jbc.271.18.10583.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsBase SequenceCHO CellsCricetinaeDNA PrimersEnzyme ActivationInsulinInsulin Receptor Substrate ProteinsMiceMolecular Sequence DataPhosphoproteinsProtein-Tyrosine KinasesProto-Oncogene ProteinsProto-Oncogene Proteins c-fynSignal TransductionSrc Homology DomainsSubstrate SpecificityConceptsSrc homology 2Grb-2Insulin stimulationTyrosine phosphorylation sitesInsulin/IGFSH2 domainSH2 proteinSignaling ComplexHomology 2Related Src kinasesPhosphorylation sitesIR-1Src kinaseExpression libraryP59fyn kinaseTyrosine residuesP59fynInsulin receptorIR proteinProteinSpecific associationComplexesKinaseReceptorsP85