Featured Publications
TAZ inhibits glucocorticoid receptor and coordinates hepatic glucose homeostasis in normal physiological states
Xu S, Liu Y, Hu R, Wang M, Stöhr O, Xiong Y, Chen L, Kang H, Zheng L, Cai S, He L, Wang C, Copps K, White M, Miao J. TAZ inhibits glucocorticoid receptor and coordinates hepatic glucose homeostasis in normal physiological states. ELife 2021, 10: e57462. PMID: 34622775, PMCID: PMC8555985, DOI: 10.7554/elife.57462.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAnimalsBlood GlucoseGluconeogenesisHomeostasisIntracellular Signaling Peptides and ProteinsLiverMice, KnockoutReceptors, GlucocorticoidConceptsGluconeogenic gene promotersBinding of GRGene promoterGlucocorticoid receptorGlucose homeostasisLigand-binding domainGlucose productionOverexpression of TAZHepatic glucose homeostasisWW domainsBlood glucose concentrationPhysiological fastingGluconeogenic genesGR response elementResponse elementNovel roleTAZNormal physiological stateGR transactivationPhysiological statePromoterMouse liverPericentral hepatocytesPathological statesGlucose concentration
2008
Inactivation of Hepatic Foxo1 by Insulin Signaling Is Required for Adaptive Nutrient Homeostasis and Endocrine Growth Regulation
Dong X, Copps K, Guo S, Li Y, Kollipara R, DePinho R, White M. Inactivation of Hepatic Foxo1 by Insulin Signaling Is Required for Adaptive Nutrient Homeostasis and Endocrine Growth Regulation. Cell Metabolism 2008, 8: 65-76. PMID: 18590693, PMCID: PMC2929667, DOI: 10.1016/j.cmet.2008.06.006.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAnimalsEndocrine GlandsFoodForkhead Transcription FactorsGrowthHomeostasisInsulinInsulin Receptor Substrate ProteinsInsulin ResistanceIntracellular Signaling Peptides and ProteinsLiverMiceMice, KnockoutNerve Tissue ProteinsPhosphoproteinsSignal TransductionConceptsInsulin signalingForkhead transcription factor FOXO1Insulin-regulated glucose homeostasisExpression of genesTranscription factor FOXO1Endocrine growth regulationNutrient homeostasisMetabolic genesStress resistancePerturbed expressionActive FoxO1Growth regulationLiver-specific deletionHepatic FoxO1Hepatic insulin resistanceBody sizePI3KHepatic Irs1FOXO1TranscriptomeSomatic growthDKO miceGenesSignalingHomeostasisStructural 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
The Repression of IRS2 Gene by ATF3, a Stress-Inducible Gene, Contributes to Pancreatic β-Cell Apoptosis
Li D, Yin X, Zmuda E, Wolford C, Dong X, White M, Hai T. The Repression of IRS2 Gene by ATF3, a Stress-Inducible Gene, Contributes to Pancreatic β-Cell Apoptosis. Diabetes 2007, 57: 635-644. PMID: 18057093, DOI: 10.2337/db07-0717.Peer-Reviewed Original ResearchMeSH KeywordsActivating Transcription Factor 3AnimalsApoptosisCell LineCells, CulturedDown-RegulationInsulinInsulin Receptor Substrate ProteinsInsulin-Secreting CellsIntracellular Signaling Peptides and ProteinsMiceMice, KnockoutPhosphoproteinsPromoter Regions, GeneticRatsStress, PhysiologicalTime FactorsConceptsStress-inducible genesIRS2 gene expressionIRS2 promoterBinding of ATF3Gene transcriptionGene expressionExpression of IRS2Chromatin immunoprecipitation assaysIRS2 genePancreatic β-cell apoptosisEnvironmental stress factorsΒ-cell apoptosisTranscription factor 3Effect of ATF3Stress signalsImmunoprecipitation assaysBeta-cell survivalTarget genesProapoptotic genesExpression of ATF3GenesTranscriptionIRS2 expressionATF3PromoterBrain IRS2 Signaling Coordinates Life Span and Nutrient Homeostasis
Taguchi A, Wartschow L, White M. Brain IRS2 Signaling Coordinates Life Span and Nutrient Homeostasis. Science 2007, 317: 369-372. PMID: 17641201, DOI: 10.1126/science.1142179.Peer-Reviewed Original ResearchMeSH KeywordsAgingAnimalsBrainCircadian RhythmCrosses, GeneticDietFemaleGlucoseHomeostasisInsulin Receptor Substrate ProteinsInsulin ResistanceIntracellular Signaling Peptides and ProteinsLongevityMaleMiceMice, KnockoutMice, TransgenicOverweightOxidation-ReductionOxygen ConsumptionPhosphoproteinsRespirationSignal TransductionSuperoxide DismutaseInsulin receptor substrate 1 (IRS‐1) plays a unique role in normal epidermal physiology
Sadagurski M, Nofech‐Mozes S, Weingarten G, White M, Kadowaki T, Wertheimer E. Insulin receptor substrate 1 (IRS‐1) plays a unique role in normal epidermal physiology. Journal Of Cellular Physiology 2007, 213: 519-527. PMID: 17508357, DOI: 10.1002/jcp.21131.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell DifferentiationCell ProliferationCells, CulturedEpidermisHumansInsulinInsulin Receptor Substrate ProteinsIntracellular Signaling Peptides and ProteinsKeratinocytesMiceMice, KnockoutPhosphoproteinsSignal TransductionConceptsNull miceIRS-1IRS-1 null miceIRS-2Skin physiologySkin cellsNormal epidermal physiologyInsulin receptor substrate-1Primary skin cellsSkin differentiationIRS-2 proteinReceptor substrate-1Skin epidermal cellsInsulin actionAdvanced stageExpression of K1Histological analysisNull skinSkin sectionsInsulin receptor substrate (IRS) proteinsEpidermal physiologyMiceSkin keratinocytesMarked decreaseEffects of inactivationAnalysis 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 treatmentINSRPlasma insulin levels predict the development of atherosclerosis when IRS2 deficiency is combined with severe hypercholesterolemia in apolipoprotein E-null mice.
Gonzalez-Navarro H, Vila-Caballer M, Pastor M, Vinue A, White M, Burks D, Andres V. Plasma insulin levels predict the development of atherosclerosis when IRS2 deficiency is combined with severe hypercholesterolemia in apolipoprotein E-null mice. Frontiers In Bioscience-Landmark 2007, 12: 2291-8. PMID: 17127239, DOI: 10.2741/2231.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApolipoproteins EAtherosclerosisBlood GlucoseDiabetes Mellitus, Type 2Diabetic AngiopathiesFemaleHypercholesterolemiaInsulinInsulin Receptor Substrate ProteinsIntracellular Signaling Peptides and ProteinsLipidsMacrophagesMaleMiceMice, KnockoutMuscle, Smooth, VascularPhosphoproteinsConceptsInsulin receptor substrate 2ApoE-/- miceDevelopment of atherosclerosisIrs2-/- miceSevere hypercholesterolemiaInsulin levelsType 2 diabetic patientsAtherosclerotic lesion burdenPre-diabetic patientsPlasma insulin levelsFat-fed miceAbsence of hyperglycaemiaDefective insulin signalingDiabetic patientsLesion burdenClinical manifestationsInsulin resistanceModerate hypercholesterolemiaApolipoprotein EGlucose levelsAtherosclerotic lesionsAtherosclerosisHypercholesterolemiaNull miceImportant modulator
2006
The reciprocal stability of FOXO1 and IRS2 creates a regulatory circuit that controls insulin signaling.
Guo S, Dunn S, White M. The reciprocal stability of FOXO1 and IRS2 creates a regulatory circuit that controls insulin signaling. Endocrinology 2006, 20: 3389-99. PMID: 16916938, DOI: 10.1210/me.2006-0092.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCells, CulturedFibroblastsForkhead Box Protein O1Forkhead Transcription FactorsInsulinInsulin Receptor Substrate ProteinsIntracellular Signaling Peptides and ProteinsMiceMice, Mutant StrainsPhosphatidylinositol 3-KinasesPhosphoproteinsProtein KinasesProto-Oncogene Proteins c-aktRecombinant ProteinsSignal TransductionTOR Serine-Threonine KinasesTyrosineConceptsInsulin stimulationWild-type mouse embryo fibroblastsInsulin-receptor substrate IRS1Metastatic mammary tumor cellsProlonged insulin stimulationMouse embryo fibroblastsTranscription factor FOXO1Substrates IRS1FoxO phosphorylationRegulatory circuitsNuclear exclusionWT MEFsTyrosine phosphorylationGene expressionMetabolic regulationEmbryo fibroblastsIRS1 expressionMammary tumor cellsIRS2 expressionCell growthIRS2AktIRS1MEFsPancreatic beta cellsRegulating insulin signaling and -cell function through IRS proteinsThis paper is one of a selection of papers published in this Special Issue, entitled Second Messengers and Phosphoproteins12th International Conference.
White M. Regulating insulin signaling and -cell function through IRS proteinsThis paper is one of a selection of papers published in this Special Issue, entitled Second Messengers and Phosphoproteins12th International Conference. Canadian Journal Of Physiology And Pharmacology 2006, 84: 725-737. PMID: 16998536, DOI: 10.1139/y06-008.Peer-Reviewed Original ResearchMeSH KeywordsDiabetes MellitusHumansHyperglycemiaInsulinInsulin Receptor Substrate ProteinsInsulin ResistanceInsulin-Secreting CellsIntracellular Signaling Peptides and ProteinsModels, BiologicalPhosphoproteinsSignal TransductionConceptsType 2 diabetesInsulin resistanceBeta-cell destructionPeripheral insulin resistanceDiabetes mellitusChronic hyperglycemiaSystemic disordersFemale infertilityInsulin secretionCardiovascular diseaseCell functionInevitable progressionComplex disorderDisordersDiabetesGreater frequencyPrevalent formInsulinPhosphoproteins12th International ConferenceAgeSecond messengerDyslipidemiaHypertensionMellitusAutoimmune
2005
Irs1 and Irs2 signaling is essential for hepatic glucose homeostasis and systemic growth
Dong X, Park S, Lin X, Copps K, Yi X, White M. Irs1 and Irs2 signaling is essential for hepatic glucose homeostasis and systemic growth. Journal Of Clinical Investigation 2005, 116: 101-114. PMID: 16374520, PMCID: PMC1319221, DOI: 10.1172/jci25735.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisBody WeightBone DensityGlucoseHomeostasisInsulin Receptor Substrate ProteinsIntracellular Signaling Peptides and ProteinsLiverMiceMice, KnockoutOrgan SizePancreasPhosphoproteinsReceptor, InsulinSignal TransductionConceptsSystemic growthHundreds of genesInsulin receptor substrateHepatic nutrient homeostasisHepatic glucose homeostasisHeterologous pathwaysNutrient homeostasisReceptor substrateGene expressionGSK3beta phosphorylationReceptor signalsHepatic gene expressionLKO miceInsulin receptorGlucose homeostasisIRS2IRS1Hepatic genesHepatic insulin receptorAkt-FoxO1 pathwayHomeostasisGenesHepatic glycogen storesLKO liversPathwayExendin-4 Uses Irs2 Signaling to Mediate Pancreatic β Cell Growth and Function*
Park S, Dong X, Fisher T, Dunn S, Omer A, Weir G, White M. Exendin-4 Uses Irs2 Signaling to Mediate Pancreatic β Cell Growth and Function*. Journal Of Biological Chemistry 2005, 281: 1159-1168. PMID: 16272563, DOI: 10.1074/jbc.m508307200.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBlood GlucoseCell LineCell SurvivalCyclic AMPDose-Response Relationship, DrugElectrophoresis, Polyacrylamide GelExenatideGenotypeGlucagon-Like Peptide-1 ReceptorGlucoseGuinea PigsHumansHyperglycemiaImmunoblottingImmunohistochemistryImmunoprecipitationInsulinInsulin Receptor Substrate ProteinsInsulin SecretionInsulin-Secreting CellsIntracellular Signaling Peptides and ProteinsIslets of LangerhansMiceMice, TransgenicModels, BiologicalModels, ChemicalPancreasPeptidesPhosphoproteinsPhosphorylationReceptor, InsulinReceptors, GlucagonReverse Transcriptase Polymerase Chain ReactionRNA, MessengerRNA, Small InterferingSignal TransductionTime FactorsVenomsConceptsGlucagon-like peptide-1 receptor agonistsPeptide-1 receptor agonistsReceptor agonistExendin-4Beta cellsProgressive beta cell lossShort-term therapeutic effectsInsulin-like growth factorBeta-cell lossProgression of diabetesBeta-cell massBeta-cell replicationBeta-cell growthPancreatic β-cell growthΒ-cell growthIrs2 branchPrevents diabetesInsulin/insulin-like growth factorCell growthInsulin secretionTherapeutic effectIRS2 expressionLong-term effectsFatal diabetesCell lossPhosphatase and Tensin Homolog Regulation of Islet Growth and Glucose Homeostasis*
Kushner J, Simpson L, Wartschow L, Guo S, Rankin M, Parsons R, White M. Phosphatase and Tensin Homolog Regulation of Islet Growth and Glucose Homeostasis*. Journal Of Biological Chemistry 2005, 280: 39388-39393. PMID: 16170201, DOI: 10.1074/jbc.m504155200.Peer-Reviewed Original ResearchConceptsInsulin/insulin-like growth factorWild typeIrs2 branchBeta-cell growthInsulin-like growth factorPhosphatase PTENGrowth factorFoxO1 phosphorylationBeta-cell massPTEN expressionAktPTENCascadeSmall isletsGlucose homeostasisInsulin productionGrowthIslet growthSufficient insulinPhosphatidylinositolTolerancePhosphorylationMiceSignalingHomeostasisAttenuation of Accumulation of Neointimal Lipid by Pioglitazone in Mice Genetically Deficient in Insulin Receptor Substrate-2 and Apolipoprotein E
Clough M, Schneider D, Sobel B, White M, Wadsworth M, Taatjes D. Attenuation of Accumulation of Neointimal Lipid by Pioglitazone in Mice Genetically Deficient in Insulin Receptor Substrate-2 and Apolipoprotein E. Journal Of Histochemistry & Cytochemistry 2005, 53: 603-610. PMID: 15872053, DOI: 10.1369/jhc.4a6590.2005.Peer-Reviewed Original ResearchMeSH KeywordsAdministration, OralAnimalsAortaApolipoproteins EArteriosclerosisHyperlipidemiasHypoglycemic AgentsInsulin Receptor Substrate ProteinsInsulin ResistanceIntracellular Signaling Peptides and ProteinsLipid MetabolismMiceMice, Inbred C57BLMice, KnockoutPhosphoproteinsPioglitazoneReceptor, InsulinThiazolidinedionesTunica IntimaConceptsInsulin resistanceApolipoprotein EAcute coronary syndromeVulnerable atherosclerotic plaquesInsulin receptor substrate 2Accumulation of lipidsCoronary syndromeProximal aortaInsulin sensitizersNeointimal accumulationAtheroma formationAortic intimaAtherosclerotic lesionsAtherosclerotic plaquesType 2PioglitazoneMiceLesionsCross-sectional areaHeterozygous deficiencyAtherogenesisSubstrate 2TreatmentLipidsAtheromaAlterations 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 effectIGFInsulin Receptor Substrate 2 Plays Diverse Cell-specific Roles in the Regulation of Glucose Transport*
Sadagurski M, Weingarten G, Rhodes C, White M, Wertheimer E. Insulin Receptor Substrate 2 Plays Diverse Cell-specific Roles in the Regulation of Glucose Transport*. Journal Of Biological Chemistry 2005, 280: 14536-14544. PMID: 15705592, DOI: 10.1074/jbc.m410227200.Peer-Reviewed Original ResearchMeSH KeywordsAdenoviridaeAnimalsBiological TransportDeoxyglucoseEpidermisFibroblastsGenotypeGlucoseHomozygoteImmunoblottingImmunoprecipitationInsulin Receptor Substrate ProteinsIntracellular Signaling Peptides and ProteinsKeratinocytesMiceMice, KnockoutPhosphatidylinositol 3-KinasesPhosphoproteinsSkinThymidineTime FactorsConceptsIRS-2Glucose transportInsulin receptor substrate-2 proteinInsulin-induced glucose transportInsulin receptor substrate 2Insulin-stimulated glucose transportIRS-1 proteinCell specific associationIRS-2 proteinClassical insulin target tissuesCell-specific mannerSkin epidermal keratinocytesIRS-PICell-specific rolePositive regulatorInsulin target tissuesCell physiologyDermal fibroblastsKO cellsEpidermal keratinocytesAkt activationPhosphatidylinositolSubstrate 2Insulin receptorProteinInsulin Receptor Substrate 2 Is Essential for Maturation and Survival of Photoreceptor Cells
Yi X, Schubert M, Peachey N, Suzuma K, Burks D, Kushner J, Suzuma I, Cahill C, Flint C, Dow M, Leshan R, King G, White M. Insulin Receptor Substrate 2 Is Essential for Maturation and Survival of Photoreceptor Cells. Journal Of Neuroscience 2005, 25: 1240-1248. PMID: 15689562, PMCID: PMC6725974, DOI: 10.1523/jneurosci.3664-04.2005.Peer-Reviewed Original ResearchMeSH KeywordsAge FactorsAnimalsAnimals, NewbornApoptosisCell SurvivalDiabetic RetinopathyEye ProteinsGene DeletionHomeodomain ProteinsHyperglycemiaHyperinsulinismInsulin Receptor Substrate ProteinsInsulin ResistanceInsulin-Like Growth Factor IIntracellular Signaling Peptides and ProteinsMiceMice, KnockoutPhosphoproteinsPhosphorylationPhotic StimulationPhotoreceptor CellsProtein Processing, Post-TranslationalProtein Serine-Threonine KinasesProto-Oncogene ProteinsProto-Oncogene Proteins c-aktRetinal Ganglion CellsSignal TransductionTrans-ActivatorsConceptsIrs2-/- micePhotoreceptor cellsPlexiform layerInsulin receptor substrate 2Insulin receptor substrateInsulin-like growth factor 1 receptorGrowth factor 1 receptorMost photoreceptor cellsInner plexiform layerOuter plexiform layerFactor 1 receptorFinal common pathwaySurvival of photoreceptorsNormal electrical functionMonths of ageWeeks of ageReceptor substrateCellular growthSubstrate 2Akt phosphorylationGanglion cellsIRS2 expressionPharmacological strategiesControl littermatesPhotoreceptor degenerationDeletion of Cdkn1b ameliorates hyperglycemia by maintaining compensatory hyperinsulinemia in diabetic mice
Uchida T, Nakamura T, Hashimoto N, Matsuda T, Kotani K, Sakaue H, Kido Y, Hayashi Y, Nakayama K, White M, Kasuga M. Deletion of Cdkn1b ameliorates hyperglycemia by maintaining compensatory hyperinsulinemia in diabetic mice. Nature Medicine 2005, 11: 175-182. PMID: 15685168, DOI: 10.1038/nm1187.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell Cycle ProteinsCell NucleusCyclin-Dependent Kinase Inhibitor p27Diabetes Mellitus, Type 2Disease Models, AnimalEnzyme InhibitorsHyperglycemiaHyperinsulinismInsulin Receptor Substrate ProteinsInsulin-Like Growth Factor IIntracellular Signaling Peptides and ProteinsIslets of LangerhansLeptinMiceMice, KnockoutPhosphoproteinsProtein Serine-Threonine KinasesProto-Oncogene ProteinsProto-Oncogene Proteins c-aktReceptors, Cell SurfaceReceptors, LeptinSignal TransductionTumor Suppressor ProteinsConceptsCyclin-dependent kinasesInsulin receptor substrate 2Cell cycle progressionPancreatic beta cell proliferationPotential new targetsCompensatory hyperinsulinemiaCycle progressionProtein p27Kip1Substrate 2Type 2 diabetes mellitusPancreatic beta cellsP27Kip1Beta-cell failureBeta-cell proliferationType 2 diabetesLong formNew targetsDeletionDiabetes mellitusDiabetic miceIslet massLeptin receptorBeta cellsAnimal modelsMice
2004
IRS‐2 mediates the antiapoptotic effect of insulin in neonatal hepatocytes
Valverde A, Fabregat I, Burks D, White M, Benito M. IRS‐2 mediates the antiapoptotic effect of insulin in neonatal hepatocytes. Hepatology 2004, 40: 1285-1294. PMID: 15565601, DOI: 10.1002/hep.20485.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnimals, NewbornApoptosisApoptosis Regulatory ProteinsBcl-2-Like Protein 11Bcl-X ProteinBlood ProteinsCarrier ProteinsEpidermal Growth FactorFemaleForkhead Box Protein O1Forkhead Transcription FactorsGene ExpressionHepatocytesHypoglycemic AgentsInsulinInsulin Receptor Substrate ProteinsIntracellular Signaling Peptides and ProteinsMaleMembrane ProteinsMiceMice, Mutant StrainsPhosphatidylinositol 3-KinasesPhosphoproteinsPregnancyProtein Serine-Threonine KinasesProto-Oncogene ProteinsProto-Oncogene Proteins c-aktProto-Oncogene Proteins c-bcl-2Signal TransductionTranscription FactorsConceptsCaspase-3 activityIRS-2Caspase-3 activationGene expressionWild-type hepatocytesDominant negative FoxO1Wild-type cellsSerum withdrawal-induced apoptosisInsulin receptor substrateWithdrawal-induced apoptosisAnti-apoptotic gene expressionImmortalized hepatocyte cell linesIRS-2 signalingPIP3 generationProapoptotic gene expressionAntiapoptotic gene expressionProlonged insulin treatmentEpidermal growth factorActive FoxO1Receptor substrateNeonatal hepatocytesProapoptotic genesAntiapoptotic genesCaspase-8Serum withdrawalInvolvement of Insulin Receptor Substrate 2 in Mammary Tumor Metastasis
Nagle J, Ma Z, Byrne M, White M, Shaw L. Involvement of Insulin Receptor Substrate 2 in Mammary Tumor Metastasis. Molecular And Cellular Biology 2004, 24: 9726-9735. PMID: 15509777, PMCID: PMC525494, DOI: 10.1128/mcb.24.22.9726-9735.2004.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisBase SequenceBreast NeoplasmsCell Line, TumorDNA, NeoplasmFemaleHumansInsulin Receptor Substrate ProteinsIntracellular Signaling Peptides and ProteinsMammary Neoplasms, ExperimentalMiceMice, Inbred C57BLMice, KnockoutMice, TransgenicMitosisNeoplasm InvasivenessPhosphoproteinsPhosphorylationConceptsIRS-2Insulin receptor substrate (IRS) proteinsMammary tumor cellsPolyoma virus middle T antigenInsulin receptor substrate 2Middle T antigenGrowth factor deprivationTumor cellsIRS-2 expressionSubstrate proteinsPyV mTMammary tumor metastasisApoptotic stimuliFactor deprivationAdaptor moleculeIncidence of metastasisMitotic cellsMammary fat padMammary tumor progressionBreast cancer metastasisHuman breast cancerSubstrate 2T antigenTumor initiationCancer metastasis