2005
Alterations in growth and apoptosis of insulin receptor substrate-1-deficient β-cells
Hennige A, Ozcan U, Okada T, Jhala U, Schubert M, White M, Kulkarni R. Alterations in growth and apoptosis of insulin receptor substrate-1-deficient β-cells. AJP Endocrinology And Metabolism 2005, 289: e337-e346. PMID: 15827066, DOI: 10.1152/ajpendo.00032.2004.Peer-Reviewed Original ResearchMeSH KeywordsAdaptation, PhysiologicalAnimalsApoptosisCell ProliferationInsulinInsulin Receptor Substrate ProteinsInsulin ResistanceIntracellular Signaling Peptides and ProteinsIslets of LangerhansIslets of Langerhans TransplantationKidneyMaleMiceMice, Inbred C57BLMice, KnockoutPhosphoproteinsSignal TransductionConceptsInsulin resistanceInsulin receptor substrateWT recipientsInsulin/IGFIRS-1 knockout miceBeta-cell proliferationBeta-cell apoptosisIslet hypoplasiaIRS-2 expressionEndogenous isletsOvert diabetesKidney capsuleIslet responseIslet functionIslet defectKnockout miceMitotic rateCompensatory increaseIslet growthDysfunctional isletsGrowth retardationTransplantation approachesΒ-cellsAntiapoptotic effectIGF
2004
Insulin receptor substrate proteins and diabetes
Lee Y, White M. Insulin receptor substrate proteins and diabetes. Archives Of Pharmacal Research 2004, 27: 361-370. PMID: 15180298, DOI: 10.1007/bf02980074.Peer-Reviewed Original ResearchConceptsInsulin receptor substrate (IRS) proteinsSubstrate proteinsPancreatic β-cell growthInsulin/IGFIntracellular signaling cascadesReceptor tyrosine kinasesΒ-cell growthCell surface receptorsIRS proteinsGrowth factor actionProtein signalingSerine phosphorylationSignaling cascadesInsulin resistanceTyrosine kinaseInsulin-like growth factor actionIrs2 branchCell growthSurface receptorsFactor actionPeripheral insulin responsePeripheral insulin resistanceIRS2ProteinImportant mechanism
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 availabilityUpregulation of insulin receptor substrate-2 in pancreatic β cells prevents diabetes
Hennige A, Burks D, Ozcan U, Kulkarni R, Ye J, Park S, Schubert M, Fisher T, Dow M, Leshan R, Zakaria M, Mossa-Basha M, White M. Upregulation of insulin receptor substrate-2 in pancreatic β cells prevents diabetes. Journal Of Clinical Investigation 2003, 112: 1521-1532. PMID: 14617753, PMCID: PMC259126, DOI: 10.1172/jci18581.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisCell SizeDiabetes Mellitus, ExperimentalDiabetes Mellitus, Type 2Dietary FatsGene Expression RegulationHumansInsulinInsulin Receptor Substrate ProteinsInsulin-Like Growth Factor IIntracellular Signaling Peptides and ProteinsIslets of LangerhansIslets of Langerhans TransplantationMaleMiceMice, Inbred C57BLMice, KnockoutMice, TransgenicPhosphoproteinsReceptor, InsulinSignal TransductionSurvival RateUp-RegulationConceptsPancreatic beta-cell functionPeripheral insulin actionBeta-cell failureBeta-cell functionType 2 diabetesIrs2-/- miceInsulin receptor substrate 2Beta-cell growthBeta cell-specific expressionPrevents diabetesObese miceTransgenic isletsInsulin secretionWT isletsIRS2 expressionPharmacological approachesBeta cellsPhysiologic responsesInsulin actionRational treatmentDiabetesInsulin/IGFCell functionMiceCell-specific expression
2002
The forkhead transcription factor Foxo1 links insulin signaling to Pdx1 regulation of pancreatic β cell growth
Kitamura T, Nakae J, Kitamura Y, Kido Y, Biggs W, Wright C, White M, Arden K, Accili D. The forkhead transcription factor Foxo1 links insulin signaling to Pdx1 regulation of pancreatic β cell growth. Journal Of Clinical Investigation 2002, 110: 1839-1847. PMID: 12488434, PMCID: PMC151657, DOI: 10.1172/jci16857.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell LineCell NucleusDiabetes Mellitus, Type 2Epithelial CellsForkhead Box Protein O1Forkhead Transcription FactorsGenes, ReporterHomeodomain ProteinsHumansInsulinInsulin Receptor Substrate ProteinsIntracellular Signaling Peptides and ProteinsIslets of LangerhansKidneyMiceMice, KnockoutMicroscopy, FluorescencePancreasPhosphoproteinsPromoter Regions, GeneticProtein IsoformsReceptor, InsulinSignal TransductionTrans-ActivatorsTranscription FactorsConceptsBeta-cell failureBeta-cell proliferationBeta cellsInsulin-producing beta cellsBeta-cell massCell proliferationInsulin receptor substrate 2Pdx1 expressionPancreatic β-cell growthΒ-cell growthTranscription factor FOXO1Pancreatic ductSubset of cellsForkhead transcription factor FOXO1Cell failureNuclear expressionInsulin/IGFRelative deficiencyMutant FoxO1Pdx1 promoterProgenitor cellsFOXO1Gene 1InsulinMice
2001
Regulation of Insulin/Insulin-like Growth Factor-1 Signaling by Proteasome-mediated Degradation of Insulin Receptor Substrate-2*
Rui L, Fisher T, Thomas J, White M. Regulation of Insulin/Insulin-like Growth Factor-1 Signaling by Proteasome-mediated Degradation of Insulin Receptor Substrate-2*. Journal Of Biological Chemistry 2001, 276: 40362-40367. PMID: 11546773, DOI: 10.1074/jbc.m105332200.Peer-Reviewed Original ResearchMeSH KeywordsAdipocytesAnimalsCarcinoma, HepatocellularDiabetes Mellitus, Type 2Down-RegulationFeedbackFibroblastsHumansInsulinInsulin Receptor Substrate ProteinsInsulin-Like Growth Factor IIntracellular Signaling Peptides and ProteinsLiver Neoplasms, ExperimentalMiceMitogen-Activated Protein KinasesOsmotic PressurePeptide HydrolasesPhosphatidylinositol 3-KinasesPhosphoproteinsProteasome Endopeptidase ComplexProtein KinasesProtein Serine-Threonine KinasesProto-Oncogene ProteinsProto-Oncogene Proteins c-aktReceptor, InsulinSignal TransductionTOR Serine-Threonine KinasesTumor Cells, CulturedUbiquitinConceptsInsulin-like growth factor-1Insulin/IGFMouse embryo fibroblastsProteasome-mediated degradationIRS-2Embryo fibroblastsInsulin/insulin-like growth factor-1 signalingInsulin receptor substrate (IRS) proteinsUbiquitin/proteasome-mediated degradationNovel negative feedback mechanismInsulin-like growth factor-1 signalingInsulin receptor substrate 2Inhibitor of phosphatidylinositolIRS-1 activationPeripheral insulin actionIGF-1 treatmentReceptor tyrosine kinasesHomologous receptor tyrosine kinasesGrowth factor-1IRS proteinsSubstrate proteinsBeta-cell survivalOsmotic stressTyrosine kinaseIRS-1Insulin/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
1998
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.
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
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.
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-1
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