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
2011
IRS-2 Deficiency Impairs NMDA Receptor-Dependent Long-term Potentiation
Martín E, Sánchez-Perez A, Trejo J, Martin-Aldana J, Jaimez M, Pons S, Umanzor C, Menes L, White M, Burks D. IRS-2 Deficiency Impairs NMDA Receptor-Dependent Long-term Potentiation. Cerebral Cortex 2011, 22: 1717-1727. PMID: 21955917, PMCID: PMC3388895, DOI: 10.1093/cercor/bhr216.Peer-Reviewed Original ResearchConceptsLong-term potentiationInduction of LTPInsulin receptor substrate 2Activation of FynPotential new componentSynaptic transmissionSynaptic plasticityWild-type controlsSubstrate 2Alzheimer's diseasePostsynaptic N-methyl-D-aspartate receptorsIRS2 expressionN-methyl-D-aspartate receptorsImpairs long-term potentiationInsulin-like growth factor IMechanistic linkNMDA receptor-dependent long-term potentiationType 2 diabeticsBasal synaptic transmissionExpression of NR2AGroups of miceGrowth factor IPaired-pulse facilitationNeurodegenerative disordersTetanus stimulation
2008
Irs2 Inactivation Suppresses Tumor Progression in Pten +/− Mice
Szabolcs M, Keniry M, Simpson L, Reid L, Koujak S, Schiff S, Davidian G, Licata S, Gruvberger-Saal S, Murty V, Nandula S, Efstratiadis A, Kushner J, White M, Parsons R. Irs2 Inactivation Suppresses Tumor Progression in Pten +/− Mice. American Journal Of Pathology 2008, 174: 276-286. PMID: 19095950, PMCID: PMC2631340, DOI: 10.2353/ajpath.2009.080086.Peer-Reviewed Original ResearchConceptsPI3KInsulin receptor substrate-2 expressionProstatic intraepithelial neoplasiaHuman prostate cancerCancer cell growthSuppresses tumor progressionIntraepithelial neoplasiaInitiation of neoplasiaProstate cancerIRS2 expressionMultiple organsExpression of MYCTumor progressionTumor samplesMiceHuman cancersMYC expressionProgressionExpression levelsPTEN levelsBasement membraneIRS2NeoplasiaTumorsCancerMuscle-Specific IRS-1 Ser→Ala Transgenic Mice Are Protected From Fat-Induced Insulin Resistance in Skeletal Muscle
Morino K, Neschen S, Bilz S, Sono S, Tsirigotis D, Reznick RM, Moore I, Nagai Y, Samuel V, Sebastian D, White M, Philbrick W, Shulman GI. Muscle-Specific IRS-1 Ser→Ala Transgenic Mice Are Protected From Fat-Induced Insulin Resistance in Skeletal Muscle. Diabetes 2008, 57: 2644-2651. PMID: 18633112, PMCID: PMC2551673, DOI: 10.2337/db06-0454.Peer-Reviewed Original ResearchMeSH KeywordsAlanineAmino Acid SubstitutionAnimalsBlotting, WesternDietary FatsFemaleGlucose Clamp TechniqueGlucose Tolerance TestImmunoprecipitationInsulinInsulin Receptor Substrate ProteinsInsulin ResistanceMaleMiceMice, Inbred C57BLMice, TransgenicMuscle, SkeletalPhosphorylationSerineTriglyceridesConceptsSerine phosphorylationIRS-1IRS-1-associated phosphatidylinositolSkeletal muscleInsulin-stimulated IRS-1-associated phosphatidylinositolWild-type transgenic miceFat-induced insulin resistanceInsulin receptor substrateTransgenic miceReceptor substrateInsulin signalingAkt phosphorylationPhosphorylationCellular mechanismsCritical roleGlucose uptakeHigh-fat feedingInsulin resistanceMuscle glucose uptakeInsulin actionVivoSerInsulin-stimulated muscle glucose uptakeImportant rolePhosphatidylinositolGenetic Deficiency of Glycogen Synthase Kinase-3β Corrects Diabetes in Mouse Models of Insulin Resistance
Tanabe K, Liu Z, Patel S, Doble B, Li L, Cras-Méneur C, Martinez S, Welling C, White M, Bernal-Mizrachi E, Woodgett J, Permutt M. Genetic Deficiency of Glycogen Synthase Kinase-3β Corrects Diabetes in Mouse Models of Insulin Resistance. PLOS Biology 2008, 6: e37. PMID: 18288891, PMCID: PMC2245985, DOI: 10.1371/journal.pbio.0060037.Peer-Reviewed Original ResearchConceptsBeta-cell massIrs2-/- miceInsulin resistanceMouse modelType 2 diabetes mellitusObese insulin-resistant individualsWhole-body glucose disposalOnset of diabetesPdx1 levelsBeta-cell functionBeta-cell lossInsulin-resistant individualsBeta-cell replicationGSK-3betaBeta-cell proliferationInsulin receptor substrate 2Cyclin-dependent kinase inhibitorDiabetes mellitusDiabetes onsetEarly diabetesPI-3K/Akt pathwayGlucose disposalGSK-3beta activityDiabetesInsulin action
2005
Reduced mitochondrial density and increased IRS-1 serine phosphorylation in muscle of insulin-resistant offspring of type 2 diabetic parents
Morino K, Petersen KF, Dufour S, Befroy D, Frattini J, Shatzkes N, Neschen S, White MF, Bilz S, Sono S, Pypaert M, Shulman GI. Reduced mitochondrial density and increased IRS-1 serine phosphorylation in muscle of insulin-resistant offspring of type 2 diabetic parents. Journal Of Clinical Investigation 2005, 115: 3587-3593. PMID: 16284649, PMCID: PMC1280967, DOI: 10.1172/jci25151.Peer-Reviewed Original ResearchMeSH KeywordsBiopsyBlood GlucoseBlotting, WesternBody Mass IndexBody WeightDiabetes Mellitus, Type 2DNA, MitochondrialFamily HealthFemaleGene Expression RegulationGlucose Clamp TechniqueGlucose Tolerance TestHumansHyperinsulinismImmunoprecipitationInsulinInsulin Receptor Substrate ProteinsInsulin ResistanceLipidsMaleMicroscopy, ElectronMicroscopy, Electron, TransmissionMitochondriaMusclesPhosphoproteinsPhosphorylationProtein Serine-Threonine KinasesReverse Transcriptase Polymerase Chain ReactionRNA, MessengerSerineSignal TransductionTime FactorsTranscription, GeneticTriglyceridesConceptsInsulin-resistant offspringIR offspringType 2 diabetesInsulin-stimulated muscle glucose uptakeType 2 diabetic parentsIntramyocellular lipid contentHyperinsulinemic-euglycemic clampMuscle glucose uptakeIRS-1 serine phosphorylationMuscle mitochondrial densityMitochondrial densityMuscle biopsy samplesSerine kinase cascadeInsulin-stimulated Akt activationDiabetic parentsInsulin resistanceControl subjectsBiopsy samplesGlucose uptakeLipid accumulationMitochondrial dysfunctionInsulin signalingAkt activationEarly defectsMuscle
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
1997
Interaction of p59fynwith Interferon-Activated Jak Kinases
Uddin S, Sher D, Alsayed Y, Pons S, Colamonici O, Fish E, White M, Platanias L. Interaction of p59fynwith Interferon-Activated Jak Kinases. Biochemical And Biophysical Research Communications 1997, 235: 83-88. PMID: 9196040, DOI: 10.1006/bbrc.1997.6741.Peer-Reviewed Original ResearchAntibodies, MonoclonalBlotting, WesternGlutathione TransferaseHumansInterferon Type IInterferon-gammaJanus Kinase 1Janus Kinase 2PhosphotyrosineProteinsProtein-Tyrosine KinasesProto-Oncogene MasProto-Oncogene ProteinsProto-Oncogene Proteins c-cblProto-Oncogene Proteins c-fynRecombinant Fusion ProteinsRecombinant ProteinsSignal TransductionSrc Homology DomainsTumor Cells, CulturedTYK2 KinaseUbiquitin-Protein Ligases