2004
Disruption of the SH2-B Gene Causes Age-Dependent Insulin Resistance and Glucose Intolerance
Duan C, Yang H, White M, Rui L. Disruption of the SH2-B Gene Causes Age-Dependent Insulin Resistance and Glucose Intolerance. Molecular And Cellular Biology 2004, 24: 7435-7443. PMID: 15314154, PMCID: PMC506995, DOI: 10.1128/mcb.24.17.7435-7443.2004.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAdipose TissueAgingAnimalsBlood GlucoseCarrier ProteinsCell LineDietary FatsGlucose IntoleranceHomeostasisHumansInsulinInsulin Receptor Substrate ProteinsInsulin ResistanceIntracellular Signaling Peptides and ProteinsIslets of LangerhansLiverMaleMiceMice, Inbred StrainsMice, KnockoutMitogen-Activated Protein KinasesMuscle, SkeletalPhosphatidylinositol 3-KinasesPhosphoproteinsProtein Serine-Threonine KinasesProto-Oncogene ProteinsProto-Oncogene Proteins c-aktReceptor, InsulinSignal TransductionConceptsSrc homology 2Insulin receptor substrate-1Insulin receptor activationInsulin receptorTyrosine phosphorylationSH2 domain-dependent mannerPleckstrin homology domain-containing adaptor proteinDomain-containing adaptor proteinDomain-dependent mannerReceptor substrate-1Skeletal muscleSH2 domainHomology 2Adaptor proteinReceptor activationSubstrate-1Physiological roleCultured cellsGlucose homeostasisERK1/2 pathwayDependent insulin resistancePhysiological enhancerSystemic deletionPhosphorylationIRS2
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 signalsInsulin receptor substrate (IRS) proteins IRS-1 and IRS-2 differential signaling in the insulin/insulin-like growth factor-I pathways in fetal brown adipocytes.
Valverde A, Lorenzo M, Pons S, White M, Benito M. Insulin receptor substrate (IRS) proteins IRS-1 and IRS-2 differential signaling in the insulin/insulin-like growth factor-I pathways in fetal brown adipocytes. Endocrinology 1998, 12: 688-97. PMID: 9605931, DOI: 10.1210/mend.12.5.0106.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAdipocytesAdipose Tissue, BrownAmino Acid SequenceAnimalsEnzyme ActivationFetusGRB2 Adaptor ProteinInsulinInsulin Receptor Substrate ProteinsInsulin-Like Growth Factor IIntracellular Signaling Peptides and ProteinsMolecular Sequence DataPhosphatidylinositol 3-KinasesPhosphoproteinsPhosphorylationProtein BindingProteinsRatsRats, WistarReceptor, InsulinSignal TransductionSrc Homology DomainsTyrosineConceptsInsulin/IGFInsulin receptor substrateIRS-1IRS-2Shc proteinsTyrosine phosphorylationInsulin receptor substrate (IRS) proteinsInsulin/insulin-like growth factorFetal rat brown adipocytesIRS-2-associated phosphatidylinositolIRS-2 tyrosine phosphorylationFetal brown adipocytesProtein kinase signal pathwayBrown adipocytesKinase signal pathwayBrown adipocyte proliferationInsulin/insulinSubstrate proteinsSH2 domainGrb-2Thermogenic differentiationFetal brown adipose tissueReceptor substrateFusion proteinInsulin-like growth factor
1997
Interaction of wild type and dominant-negative p55PIK regulatory subunit of phosphatidylinositol 3-kinase with insulin-like growth factor-1 signaling proteins.
Mothe I, Delahaye L, Filloux C, Pons S, White M, Van Obberghen E. Interaction of wild type and dominant-negative p55PIK regulatory subunit of phosphatidylinositol 3-kinase with insulin-like growth factor-1 signaling proteins. Endocrinology 1997, 11: 1911-23. PMID: 9415396, DOI: 10.1210/mend.11.13.0029.Peer-Reviewed Original ResearchMeSH KeywordsBinding SitesBiological TransportFungal ProteinsGenes, ReporterGlucoseInsulinInsulin Receptor Substrate ProteinsInsulin-Like Growth Factor IMutagenesis, Site-DirectedPhosphatidylinositol 3-KinasesPhosphoproteinsPhosphorylationPrecipitin TestsReceptor, IGF Type 1Recombinant Fusion ProteinsSaccharomyces cerevisiaeSignal TransductionConceptsTwo-hybrid systemInsulin receptor substrate-1Receptor substrate-1Regulatory subunitSubstrate-1Src homology 2 domainInter-SH2 domainProtein-protein interactionsInhibitor of PIAmino acids 203Dominant negative mutantInsulin-stimulated glucose transportIGF-IRInsulin-like growth factor 1 receptorNH2 terminus regionDominant negative actionGrowth factor 1 receptorP110alpha catalytic subunitIGF-I stimulationSH2 domainFactor 1 receptorCatalytic subunitTyrosine phosphorylationWild typeP55PIKThe IRS-pathway operates distinctively from the Stat-pathway in hematopoietic cells and transduces common and distinct signals during engagement of the insulin or interferon-alpha receptors.
Uddin S, Fish E, Sher D, Gardziola C, Colamonici O, Kellum M, Pitha P, White M, Platanias L. The IRS-pathway operates distinctively from the Stat-pathway in hematopoietic cells and transduces common and distinct signals during engagement of the insulin or interferon-alpha receptors. Blood 1997, 90: 2574-82. PMID: 9326223.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBurkitt LymphomaDNA-Binding ProteinsHematopoietic Stem CellsHumansInsulinInsulin Receptor Substrate ProteinsInsulin-Like Growth Factor IInterferon-alphaIntracellular Signaling Peptides and ProteinsLeukemia, Myelomonocytic, AcuteLeukemia-Lymphoma, Adult T-CellMiceMultiple MyelomaNeoplasm ProteinsPhosphoproteinsReceptor, InsulinReceptor, Interferon alpha-betaReceptors, InterferonSignal TransductionSrc Homology DomainsSTAT1 Transcription FactorSTAT2 Transcription FactorSTAT3 Transcription FactorTrans-ActivatorsTumor Cells, CulturedConceptsSTAT pathwaySH2 domainHematopoietic cellsInsulin/insulin-like growth factorIRS pathwayDistinct downstream signalsTHP-1 cellsIRS-1 functionInsulin/IGFActivator of transcriptionInsulin receptor substrateDistinct signalsIFN-alphaHuman myelomonocytic cellsDocking proteinMouse myeloid cellsGrb-2P85 subunitInterferon alpha receptorSTAT-2Receptor substrateVesicular stomatitis virusSignal transducerIRS-2IRS-1The 60 kDa Insulin Receptor Substrate Functions Like an IRS Protein (pp60IRS3) in Adipose Cells †
Smith-Hall J, Pons S, Patti M, Burks D, Yenush L, Sun X, Kahn C, White M. The 60 kDa Insulin Receptor Substrate Functions Like an IRS Protein (pp60IRS3) in Adipose Cells †. Biochemistry 1997, 36: 8304-8310. PMID: 9204876, DOI: 10.1021/bi9630974.Peer-Reviewed Original ResearchMeSH KeywordsAdipocytesAnimalsImmunosorbent TechniquesInsulinInsulin Receptor Substrate ProteinsIntracellular Signaling Peptides and ProteinsMaleMiceMolecular WeightPhosphatidylinositol 3-KinasesPhosphoproteinsPhosphotransferases (Alcohol Group Acceptor)PhosphotyrosineRatsRats, Sprague-DawleyReceptor, InsulinTestisConceptsIRS-1IRS proteinsInsulin receptor substrates functionIRS-2IRS protein familyTyrosine phosphorylated proteinsInsulin receptor signalsInsulin receptor substratePTB domainNPXY motifSH2 domainProtein familyPhosphorylated proteinsReceptor substrateInsulin stimulationReceptor signalsSubstrate functionP85New memberProteinRat adipocytesAdipose cellsAlternate pathwayFunctional characteristicsSynthetic peptidesThe IRS-2 gene on murine chromosome 8 encodes a unique signaling adapter for insulin and cytokine action.
Sun X, Pons S, Wang L, Zhang Y, Yenush L, Burks D, Myers M, Glasheen E, Copeland N, Jenkins N, Pierce J, White M. The IRS-2 gene on murine chromosome 8 encodes a unique signaling adapter for insulin and cytokine action. Endocrinology 1997, 11: 251-62. PMID: 9013772, DOI: 10.1210/mend.11.2.9885.Peer-Reviewed Original ResearchMeSH Keywords3T3 CellsAmino Acid SequenceAnimalsBase SequenceCell DifferentiationCells, CulturedChromosome MappingChromosomesCytokinesInsulinInsulin Receptor Substrate ProteinsInterleukin-4Intracellular Signaling Peptides and ProteinsMiceMolecular Sequence DataPhosphoproteinsPhosphorylationSequence Homology, Amino AcidSignal TransductionTissue DistributionTyrosineConceptsMurine chromosome 8IRS-2IRS-1IRS-2 geneIRS proteinsExpression patternsSrc homology 2 domainChromosome 8Recombinant SH2 domainsSpecific expression patternsMurine chromosome 1Amino acid sequenceDifferential tyrosine phosphorylationMurine hematopoietic cellsDistinct phosphorylation patternsSH2 domainSignal transductionSingle exonPhosphorylation patternTyrosine phosphorylationIL-4 stimulationAcid sequenceChromosome 1Signaling adapterCytokine signaling
1996
The 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
1993
Pleiotropic Insulin Signals are Engaged by Multisite Phosphorylation of IRS-1
Sun X, Crimmins D, Myers M, Miralpeix M, White M. Pleiotropic Insulin Signals are Engaged by Multisite Phosphorylation of IRS-1. Molecular And Cellular Biology 1993, 13: 7418-7428. DOI: 10.1128/mcb.13.12.7418-7428.1993.Peer-Reviewed Original ResearchSrc homology 2IRS-1SH2 domainInsulin signalingPotential tyrosine phosphorylation sitesTyrosine residuesSrc homology 2 domainSrc homology 2 proteinAmino-terminal SH2 domainInsulin stimulationPhosphorylation of tyrosine residuesTyrosine phosphorylation sitesMultisite docking proteinInsulin signal transmissionInsulin receptor substrateInsulin receptor kinaseInsulin-stimulated phosphorylationDownstream regulatory elementsPurified insulin receptorYMXM motifsActivating insulin receptor kinaseDocking proteinMultisite phosphorylationPhosphorylation sitesRegulatory elements