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 availabilityInsulin Receptor Substrate-2 Deficiency Impairs Brain Growth and Promotes Tau Phosphorylation
Schubert M, Brazil D, Burks D, Kushner J, Ye J, Flint C, Farhang-Fallah J, Dikkes P, Warot X, Rio C, Corfas G, White M. Insulin Receptor Substrate-2 Deficiency Impairs Brain Growth and Promotes Tau Phosphorylation. Journal Of Neuroscience 2003, 23: 7084-7092. PMID: 12904469, PMCID: PMC6740672, DOI: 10.1523/jneurosci.23-18-07084.2003.Peer-Reviewed Original ResearchMeSH KeywordsAge FactorsAnimalsApoptosisBody WeightBrainCell CountCell DivisionCell SurvivalCells, CulturedCerebellumCrosses, GeneticEnzyme InhibitorsHeterozygoteIn Situ Nick-End LabelingInsulin Receptor Substrate ProteinsIntracellular Signaling Peptides and ProteinsMiceMice, KnockoutNeuronsOrgan SizePhosphoproteinsPhosphorylationReceptor, IGF Type 1Signal TransductionTau ProteinsConceptsMolecular linkInsulin receptor substrate (IRS) proteinsBrain growthNeurodegenerative diseasesPancreatic beta-cell functionPeripheral insulin actionSubstrate proteinsBeta-cell functionTyrosine phosphorylationLike growth factorIrs2 branchInsulin resistanceTau phosphorylationIRS2 geneNeuronal proliferationInsulin actionMouse brainInsulin-IGFGrowth factorPhosphorylationIRS2DiabetesBody growthDiseaseMice
2002
Specificity of Interleukin-2 Receptor γ Chain Superfamily Cytokines Is Mediated by Insulin Receptor Substrate-dependent Pathway*
Xiao H, Yin T, Wang X, Uchida T, Chung J, White M, Yang Y. Specificity of Interleukin-2 Receptor γ Chain Superfamily Cytokines Is Mediated by Insulin Receptor Substrate-dependent Pathway*. Journal Of Biological Chemistry 2002, 277: 8091-8098. PMID: 11788580, DOI: 10.1074/jbc.m106650200.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAmino Acid MotifsAnimalsCell DivisionCell LineCytokinesDose-Response Relationship, DrugEnzyme InhibitorsGRB2 Adaptor ProteinInsulin Receptor Substrate ProteinsInterleukin-4Interleukin-9MicePhosphatidylinositol 3-KinasesPhosphoproteinsPhosphorylationPlasmidsProtein BindingProtein Structure, TertiaryProteinsReceptors, Interleukin-2Signal TransductionTransfectionTyrosineConceptsIRS proteinsCytokine specificityIL-4-mediated functionsPleckstrin homology domainJak tyrosine kinasesUnique biological functionsPI3K activityPhosphotyrosine bindingHomology domainPH domainSHP-2Different structural domainsPhosphatidylinositol 3IL-4 stimulationBinding domainsIL-2 receptor gamma chainBiological functionsPathways workProliferative effectTyrosine kinaseIRS-2IRS-1Structural domainsAkt activationIRS-4Stat6 and IRS-2 Cooperate in Interleukin 4 (IL-4)-Induced Proliferation and Differentiation but Are Dispensable for IL-4-Dependent Rescue from Apoptosis
Wurster A, Withers D, Uchida T, White M, Grusby M. Stat6 and IRS-2 Cooperate in Interleukin 4 (IL-4)-Induced Proliferation and Differentiation but Are Dispensable for IL-4-Dependent Rescue from Apoptosis. Molecular And Cellular Biology 2002, 22: 117-126. PMID: 11739727, PMCID: PMC134231, DOI: 10.1128/mcb.22.1.117-126.2002.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisCell Cycle ProteinsCell DifferentiationCell DivisionCell SeparationCells, CulturedCyclin-Dependent Kinase Inhibitor p27Enzyme InhibitorsFlow CytometryInsulin Receptor Substrate ProteinsInterleukin-4Intracellular Signaling Peptides and ProteinsMiceMice, KnockoutPhosphatidylinositol 3-KinasesPhosphoproteinsSignal TransductionSTAT6 Transcription FactorTh2 CellsT-LymphocytesTrans-ActivatorsTumor Suppressor ProteinsConceptsIRS-2Protein tyrosine phosphatase activityProtein tyrosine phosphatase inhibitorTyrosine phosphatase activityTyrosine phosphatase inhibitorWild-type cellsIL-4 signal transductionIRS-2 expressionIL-4-induced proliferationCDK inhibitor p27Kip1Antiapoptotic effectPrimary T cellsPhosphatase inhibitorCytoplasmic tailSignal transductionDifferentiation eventsCooperative regulationGene expressionAntiapoptotic signalsCell developmentAntiapoptotic activityInterleukin-4 receptorPhosphatase activityPrimary lymphocytesSTAT6
2001
IRS proteins and beta-cell function.
Burks D, White M. IRS proteins and beta-cell function. Diabetes 2001, 50: s140. PMID: 11272176, DOI: 10.2337/diabetes.50.2007.s140.Peer-Reviewed Original ResearchConceptsInsulin receptor substrateIRS proteinsIRS protein familyBeta-cell functionBeta-cell massClassical insulin target tissuesDownstream effector pathwaysPeripheral insulin resistanceIRS-2 geneInsulin resistanceProtein familyInsulin target tissuesReceptor substrateIRS-1Effector pathwaysPancreatic beta-cell massInsulin secretory reserveGrowth-promoting actionProteinBeta-cell dysfunctionSomatic growthType 2 diabetesCritical roleDiabetic phenotypeRegulationRegulation of Protein Synthesis by Insulin Through IRS-1
Mendez R, Welsh G, Kleijn M, Myers M, White M, Proud C, Rhoads R. Regulation of Protein Synthesis by Insulin Through IRS-1. Progress In Molecular And Subcellular Biology 2001, 26: 49-93. PMID: 11575167, DOI: 10.1007/978-3-642-56688-2_3.Peer-Reviewed Original ResearchAnimalsCalcium-Calmodulin-Dependent Protein KinasesCell DivisionCell LineEnzyme ActivationEukaryotic Initiation Factor-2BGlycogen Synthase Kinase 3HumansInsulinInsulin Receptor Substrate ProteinsIntracellular Signaling Peptides and ProteinsMiceMitogen-Activated Protein KinasesModels, BiologicalPhosphatidylinositol 3-KinasesPhosphoproteinsProtein BiosynthesisProtein KinasesProtein Tyrosine Phosphatase, Non-Receptor Type 11Protein Tyrosine Phosphatase, Non-Receptor Type 6Protein Tyrosine PhosphatasesRatsReceptor, InsulinSignal TransductionSirolimusTOR Serine-Threonine Kinases
1999
Stimulation of pancreatic beta-cell proliferation by growth hormone is glucose-dependent: signal transduction via janus kinase 2 (JAK2)/signal transducer and activator of transcription 5 (STAT5) with no crosstalk to insulin receptor substrate-mediated mitogenic signalling.
Cousin S, Hügl S, Myers M, White M, Reifel-Miller A, Rhodes C. Stimulation of pancreatic beta-cell proliferation by growth hormone is glucose-dependent: signal transduction via janus kinase 2 (JAK2)/signal transducer and activator of transcription 5 (STAT5) with no crosstalk to insulin receptor substrate-mediated mitogenic signalling. Biochemical Journal 1999, 344 Pt 3: 649-58. PMID: 10585851, PMCID: PMC1220686, DOI: 10.1042/0264-6021:3440649.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAdaptor Proteins, Vesicular TransportAnimalsCell DivisionCell LineDNA-Binding ProteinsGlucoseGRB2 Adaptor ProteinGrowth HormoneInsulin Receptor Substrate ProteinsInsulin-Like Growth Factor IIntracellular Signaling Peptides and ProteinsIslets of LangerhansJanus Kinase 2Milk ProteinsMitogen-Activated Protein KinasesPhosphoproteinsPhosphorylationProteinsProtein-Tyrosine KinasesProto-Oncogene ProteinsRatsRibosomal Protein S6 KinasesShc Signaling Adaptor ProteinsSignal TransductionSon of Sevenless Protein, DrosophilaSrc Homology 2 Domain-Containing, Transforming Protein 1STAT5 Transcription FactorTrans-ActivatorsConceptsINS-1 cell proliferationSignal transduction pathwaysSignal transductionCell proliferationKinase 2Sevenless-1 proteinMitogenic signal transduction pathwaysJAK2/STAT5 pathwayMitogen-activated protein kinaseInsulin receptor substrateBeta-cell proliferationRat growth hormoneJAK2/STAT5Pancreatic beta cell proliferationMitogenic signalingS6 kinaseProtein kinaseProtein associationTranscription 5Beta-cell lineReceptor substrateDifferent mitogenicRat beta-cell lineDownstream activationIRS-2
1998
The Pleckstrin Homology and Phosphotyrosine Binding Domains of Insulin Receptor Substrate 1 Mediate Inhibition of Apoptosis by Insulin
Yenush L, Zanella C, Uchida T, Bernal D, White M. The Pleckstrin Homology and Phosphotyrosine Binding Domains of Insulin Receptor Substrate 1 Mediate Inhibition of Apoptosis by Insulin. Molecular And Cellular Biology 1998, 18: 6784-6794. PMID: 9774692, PMCID: PMC109262, DOI: 10.1128/mcb.18.11.6784.Peer-Reviewed Original ResearchMeSH KeywordsApoptosisCalcium-Calmodulin-Dependent Protein KinasesCell DivisionCell LineCell SurvivalChromonesDNAInsulinInsulin Receptor Substrate ProteinsInterleukin-3MorpholinesPhosphatidylinositol 3-KinasesPhosphoproteinsPhosphorylationPhosphotyrosineReceptor, InsulinRecombinant Fusion ProteinsRibosomal Protein S6 KinasesConceptsPhosphotyrosine-binding (PTB) domainTyrosine phosphorylation sitesPleckstrin homologyIRS-1 proteinIRS-1Phosphorylation sitesInsulin receptorBinding domainsInsulin receptor substrate (IRS) proteinsReceptor-mediated tyrosine phosphorylationInsulin stimulationChimeric insulin receptorsPKB/AktIL-3 withdrawalIRS proteinsSubstrate proteinsPTB domainKinase cascadeMediated phosphorylationInhibition of apoptosisMyeloid progenitor cellsDiverse biological effectsPhosphatidylinositol 3Protein kinaseTyrosine phosphorylationThe 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 signalsInsulin-like Growth Factor I (IGF-I)-stimulated Pancreatic β-Cell Growth Is Glucose-dependent SYNERGISTIC ACTIVATION OF INSULIN RECEPTOR SUBSTRATE-MEDIATED SIGNAL TRANSDUCTION PATHWAYS BY GLUCOSE AND IGF-I IN INS-1 CELLS*
Hügl S, White M, Rhodes C. Insulin-like Growth Factor I (IGF-I)-stimulated Pancreatic β-Cell Growth Is Glucose-dependent SYNERGISTIC ACTIVATION OF INSULIN RECEPTOR SUBSTRATE-MEDIATED SIGNAL TRANSDUCTION PATHWAYS BY GLUCOSE AND IGF-I IN INS-1 CELLS*. Journal Of Biological Chemistry 1998, 273: 17771-17779. PMID: 9651378, DOI: 10.1074/jbc.273.28.17771.Peer-Reviewed Original ResearchConceptsInsulin-like growth factor IGrowth factor IBeta-cell proliferationINS-1 cell proliferationCell proliferationFactor IMM glucoseCombination of IGFPancreatic β-cell growthPancreatic beta-cell lineBeta-cell lineΒ-cell growthINS-1 cellsNM IGFBeta-cell mitogenesisCertain growth factorsSignaling mechanismSignal transduction pathwaysGlucose metabolismIGFCell proliferation rateGrowth factorIRS-2Transduction pathwaysGlucose concentrationA specific increased expression of insulin receptor substrate 2 in pancreatic beta-cell lines is involved in mediating serum-stimulated beta-cell growth.
Schuppin G, Pons S, Hügl S, Aiello L, King G, White M, Rhodes C. A specific increased expression of insulin receptor substrate 2 in pancreatic beta-cell lines is involved in mediating serum-stimulated beta-cell growth. Diabetes 1998, 47: 1074-1085. PMID: 9648831, DOI: 10.2337/diabetes.47.7.1074.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBase SequenceBloodCell DifferentiationCell DivisionDNAGene ExpressionGenes, fosGenes, junInsulin Receptor Substrate ProteinsInsulinomaIntracellular Signaling Peptides and ProteinsIslets of LangerhansMitogensMolecular Sequence DataPancreatic NeoplasmsPhosphoproteinsRatsRetroelementsRNA, MessengerSignal TransductionTumor Cells, CulturedConceptsSignal transduction pathwaysIRS-2 expressionPancreatic beta-cell lineIRS-2Protein kinaseTransduction pathwaysBeta-cell lineGene expressionIRS-2 gene expressionSevenless-1 proteinBeta-cell growthDifferential mRNA display analysisMitogen-activated protein kinaseDifferential gene expressionTyrosine protein kinaseInsulin receptor substrate 2Insulinoma cellsInsulin receptor substrateGene candidate approachSerum-stimulated DNA synthesisPancreatic beta-cell growthRibosomal proteinsProtein complexesMRNA levelsBeta-cells contributes
1997
Janus Kinase-dependent Activation of Insulin Receptor Substrate 1 in Response to Interleukin-4, Oncostatin M, and the Interferons*
Burfoot M, Rogers N, Watling D, Smith J, Pons S, Paonessaw G, Pellegrini S, White M, Kerr I. Janus Kinase-dependent Activation of Insulin Receptor Substrate 1 in Response to Interleukin-4, Oncostatin M, and the Interferons*. Journal Of Biological Chemistry 1997, 272: 24183-24190. PMID: 9305869, DOI: 10.1074/jbc.272.39.24183.Peer-Reviewed Original ResearchConceptsInsulin receptor substrate-1Receptor substrate-1IRS-1IRS proteinsOncostatin MSubstrate-1Protein tyrosine kinasesKinase-dependent activationActivation of phosphatidylinositolJanus kinase (JAK) familyMutant cell linesHuman fibrosarcoma cell lineCell linesInsulin-like growth factor receptorHuman fibrosarcoma cellsKinase familyGrowth factor receptorFibrosarcoma cell lineIRS-2Cytokine receptorsType I interferonJAK1PhosphorylationAntiviral responseFibrosarcoma cells
1996
YMXM Motifs and Signaling by an Insulin Receptor Substrate 1 Molecule without Tyrosine Phosphorylation Sites
Myers M, Zhang Y, Aldaz G, Grammer T, Glasheen E, Yenush L, Wang L, Sun X, Blenis J, Pierce J, White M. YMXM Motifs and Signaling by an Insulin Receptor Substrate 1 Molecule without Tyrosine Phosphorylation Sites. Molecular And Cellular Biology 1996, 16: 4147-4155. PMID: 8754813, PMCID: PMC231411, DOI: 10.1128/mcb.16.8.4147.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceCell DivisionCell LineDNA ReplicationEnzyme ActivationInsulinInsulin Receptor Substrate ProteinsMolecular Sequence DataMutagenesis, Site-DirectedPhosphatidylinositol 3-KinasesPhosphoproteinsPhosphotransferases (Alcohol Group Acceptor)PhosphotyrosineProtein Serine-Threonine KinasesReceptor, InsulinRecombinant ProteinsRibosomal Protein S6 KinasesSignal TransductionStructure-Activity RelationshipConceptsTyrosine phosphorylation sitesPotential tyrosine phosphorylation sitesYMXM motifsPhosphorylation sitesIRS-1SH2 proteinTyrosine phosphorylationSrc homology 2 domainIRS-1 moleculeWild-type IRS-1Insulin receptor substrate-1Mitogen-activated protein kinaseInsulin-stimulated mitogenesisReceptor substrate-1IRS proteinsProtein kinaseMitogenic signalsMitogenic responseSubstrate-1Mitogenic sensitivityInsulin signalingInsulin stimulationPhosphotidylinositolRedundant motifsProteinThe Drosophila Insulin Receptor Activates Multiple Signaling Pathways but Requires Insulin Receptor Substrate Proteins for DNA Synthesis
Yenush L, Fernandez R, Myers M, Grammer T, Sun X, Blenis J, Pierce J, Schlessinger J, White M. The Drosophila Insulin Receptor Activates Multiple Signaling Pathways but Requires Insulin Receptor Substrate Proteins for DNA Synthesis. Molecular And Cellular Biology 1996, 16: 2509-2517. PMID: 8628319, PMCID: PMC231240, DOI: 10.1128/mcb.16.5.2509.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsCalcium-Calmodulin-Dependent Protein KinasesCell DivisionCell LineDNADrosophila melanogasterEnzyme ActivationHumansInsulinInsulin Receptor Substrate ProteinsMolecular Sequence DataPhosphatidylinositol 3-KinasesPhosphoproteinsPhosphorylationPhosphotransferases (Alcohol Group Acceptor)PhosphotyrosineProtein Serine-Threonine KinasesReceptor, InsulinRecombinant ProteinsRibosomal Protein S6 KinasesSequence Homology, Amino AcidSignal TransductionThymidineConceptsDrosophila insulin receptorHuman insulin receptorInsulin receptor substrate (IRS) proteinsIRS-1Insulin receptorSubstrate proteinsTyrosine phosphorylation sitesMitogen-activated protein kinaseInsulin-stimulated mitogenesisMultiple signaling pathwaysIRS proteinsMammalian counterpartsYXXM motifsPhosphorylation sitesMammalian cellsTyrosine autophosphorylationProtein kinaseTyrosine phosphorylationSignaling pathwaysPhosphatidylinositolTerminal extensionDNA synthesisProteinHDIRP70S6k