2016
Insulin receptor substrate-1 deficiency drives a proinflammatory phenotype in KRAS mutant lung adenocarcinoma
Metz H, Kargl J, Busch S, Kim K, Kurland B, Abberbock S, Randolph-Habecker J, Knoblaugh S, Kolls J, White M, Houghton A. Insulin receptor substrate-1 deficiency drives a proinflammatory phenotype in KRAS mutant lung adenocarcinoma. Proceedings Of The National Academy Of Sciences Of The United States Of America 2016, 113: 8795-8800. PMID: 27439864, PMCID: PMC4978299, DOI: 10.1073/pnas.1601989113.Peer-Reviewed Original ResearchConceptsInsulin receptor substrate-1Janus kinase/signal transducerKinase/signal transducerTumor burdenActivator of transcriptionReceptor substrate-1IRS-1 deficiencyKRAS-mutant lung adenocarcinomaInsulin-like growth factor receptorAdenoviral Cre recombinaseIL-22 receptorMutant lung adenocarcinomaTumor-promoting inflammationAdaptor proteinSignificant survival disadvantageGrowth factor receptorSignal transducerSubstrate-1PI3KProinflammatory phenotypeLung cancerLung adenocarcinomaMutant subgroupTissue microarrayCre recombinase
2011
Regulation of glucose homeostasis through a XBP-1–FoxO1 interaction
Zhou Y, Lee J, Reno C, Sun C, Park S, Chung J, Lee J, Fisher S, White M, Biddinger S, Ozcan U. Regulation of glucose homeostasis through a XBP-1–FoxO1 interaction. Nature Medicine 2011, 17: 356-365. PMID: 21317886, PMCID: PMC3897616, DOI: 10.1038/nm.2293.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBlood GlucoseDisease Models, AnimalDNA-Binding ProteinsForkhead Box Protein O1Forkhead Transcription FactorsGlucoseHomeostasisHydrolysisInsulin ResistanceLiverMiceMutationPhosphorylationReceptor, InsulinRegulatory Factor X Transcription FactorsSignal TransductionTranscription FactorsX-Box Binding Protein 1
2009
Foxo1 integrates insulin signaling with mitochondrial function in the liver
Cheng Z, Guo S, Copps K, Dong X, Kollipara R, Rodgers J, Depinho R, Puigserver P, White M. Foxo1 integrates insulin signaling with mitochondrial function in the liver. Nature Medicine 2009, 15: 1307-1311. PMID: 19838201, PMCID: PMC3994712, DOI: 10.1038/nm.2049.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphateAnimalsCells, CulturedElectron Transport Chain Complex ProteinsForkhead Box Protein O1Forkhead Transcription FactorsGene Expression RegulationHeme Oxygenase-1HepatocytesInsulinInsulin Receptor Substrate ProteinsLiverMembrane Potential, MitochondrialMembrane ProteinsMiceMice, KnockoutMicroscopy, Electron, TransmissionMitochondriaMutationNADPeroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alphaSignal TransductionTrans-ActivatorsTranscription Factors
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
Analysis of compensatory β-cell response in mice with combined mutations of Insr and Irs2
Kim J, Kido Y, Scherer P, White M, Accili D. Analysis of compensatory β-cell response in mice with combined mutations of Insr and Irs2. AJP Endocrinology And Metabolism 2007, 292: e1694-e1701. PMID: 17299086, DOI: 10.1152/ajpendo.00430.2006.Peer-Reviewed Original ResearchMeSH KeywordsAdaptation, PhysiologicalAdiponectinAdipose TissueAnimalsAnimals, NewbornDiabetes MellitusGlucose Tolerance TestGrowth DisordersHyperinsulinismInsulinInsulin Receptor Substrate ProteinsInsulin ResistanceInsulin-Secreting CellsIntracellular Signaling Peptides and ProteinsLeptinLiverMiceMice, Inbred StrainsMice, KnockoutMuscle, SkeletalMutationOrgan SizeOsmolar ConcentrationPhosphatidylinositol 3-KinasesPhosphoproteinsProto-Oncogene Proteins c-aktReceptor, InsulinConceptsBeta-cell dysfunctionBeta-cell massInsulin resistanceInsulin secretionType 2 diabetes resultsCompensatory insulin secretionBeta-cell responseImpaired insulin actionType 2 diabetesΒ-cell responseBeta-cell growthBeta-cell physiologyDiabetes resultsInsulin levelsMetabolic controlInsulin actionProgressive deteriorationDiabetesRobust increaseDysfunctionCompensatory responseMiceSecretionComprehensive treatmentINSR
2004
Signaling Pathways: The Benefits of Good Communication
Fisher T, White M. Signaling Pathways: The Benefits of Good Communication. Current Biology 2004, 14: r1005-r1007. PMID: 15589136, DOI: 10.1016/j.cub.2004.11.024.Peer-Reviewed Original Research
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
2000
Contrasting Effects of IRS-1 Versus IRS-2 Gene Disruption on Carbohydrate and Lipid Metabolism in Vivo *
Previs S, Withers D, Ren J, White M, Shulman G. Contrasting Effects of IRS-1 Versus IRS-2 Gene Disruption on Carbohydrate and Lipid Metabolism in Vivo *. Journal Of Biological Chemistry 2000, 275: 38990-38994. PMID: 10995761, DOI: 10.1074/jbc.m006490200.Peer-Reviewed Original ResearchMeSH KeywordsAdipose TissueAnimalsCarbohydrate MetabolismFatty Acids, NonesterifiedFood DeprivationGas Chromatography-Mass SpectrometryGlucoseGlycerolInsulinInsulin Receptor Substrate ProteinsIntracellular Signaling Peptides and ProteinsLipid MetabolismLiverMaleMiceMusclesMutationPhenotypePhosphoproteinsRadioimmunoassayTime FactorsConceptsLipid metabolismInsulin resistanceIRS-2Glucose utilizationPlasma free fatty acid concentrationsWhole-body glucose utilizationGlycerol turnoverFree fatty acid concentrationsMarked insulin resistancePeripheral glucose metabolismPeripheral glucose utilizationHyperinsulinemic-euglycemic clampEndogenous glucose productionIRS-1Effect of insulinHepatic glycogen synthesisWT miceFatty acid concentrationsInsulin receptor substrateGlucose metabolismFasted miceAdipose tissueReduced suppressionGlucose productionMiceTissue-specific insulin resistance in mice with mutations in the insulin receptor, IRS-1, and IRS-2
Kido Y, Burks D, Withers D, Bruning J, Kahn C, White M, Accili D. Tissue-specific insulin resistance in mice with mutations in the insulin receptor, IRS-1, and IRS-2. Journal Of Clinical Investigation 2000, 105: 199-205. PMID: 10642598, PMCID: PMC377430, DOI: 10.1172/jci7917.Peer-Reviewed Original ResearchMeSH KeywordsAdipose TissueAnimalsBlood GlucoseCell SizeDiabetes Mellitus, Type 2Disease Models, AnimalHeterozygoteHomozygoteHyperglycemiaInsulinInsulin Receptor Substrate ProteinsInsulin ResistanceIntracellular Signaling Peptides and ProteinsIslets of LangerhansLiverMaleMiceMice, KnockoutMuscle, SkeletalMutationOrgan SpecificityPhosphatidylinositol 3-KinasesPhosphoproteinsReceptor, InsulinConceptsBeta-cell hyperplasiaSevere insulin resistanceInsulin resistanceSkeletal muscleInsulin actionAltered beta-cell functionCompensatory beta-cell hyperplasiaMild insulin resistanceTissue-specific insulin resistanceBeta-cell functionUnderlying metabolic abnormalitiesType 2 diabetesInsulin receptorHeterozygous null mutationsDiabetic miceMetabolic abnormalitiesInsulin receptor substrateAdipose tissueRole of IRSType 2MiceHyperplasiaLiverMuscleIRS-2
1999
Early biochemical events in insulin-stimulated fluid phase endocytosis
Pitterle D, Sperling R, Myers M, White M, Blackshear P. Early biochemical events in insulin-stimulated fluid phase endocytosis. American Journal Of Physiology 1999, 276: e94-e105. PMID: 9886955, DOI: 10.1152/ajpendo.1999.276.1.e94.Peer-Reviewed Original ResearchConceptsInsulin receptor substrate-1Fluid-phase endocytosisMitogen-activated protein kinase kinaseRat-1 cellsInsulin receptorDominant negative mutant RasHematopoietic precursor cell lineBat cellsHIRc-B cellsInhibitor of PIProtein kinase kinaseWild-type RasMEK inhibitor PD 98059Active insulin receptorEndogenous IRS-1Receptor substrate-1Inhibitor PD 98059Certain cell typesPrecursor cell lineInitial molecular mechanismsIRS-1 expressionKinase kinaseEarly biochemical eventsMutant RasSubstrate-1