2016
IRS proteins and diabetic complications
Lavin D, White M, Brazil D. IRS proteins and diabetic complications. Diabetologia 2016, 59: 2280-2291. PMID: 27514532, PMCID: PMC5506098, DOI: 10.1007/s00125-016-4072-7.Peer-Reviewed Original ResearchConceptsIRS proteinsType 2 diabetesDiabetic complicationsMitogen-activated protein kinaseElicit cellular responsesCoronary artery diseaseElevated blood glucoseComplications of diabetesProtein kinaseDownstream effectorsAdaptor moleculeInsulin signalingCellular responsesNumber of organsInsulin receptorMacrovascular complicationsMicrovascular complicationsArtery diseasePatient morbidityBlood glucoseProteinMale micePatient outcomesCell proliferationComplications
2013
Phosphatidylcholine Transfer Protein Interacts with Thioesterase Superfamily Member 2 to Attenuate Insulin Signaling
Ersoy B, Tarun A, D’Aquino K, Hancer N, Ukomadu C, White M, Michel T, Manning B, Cohen D. Phosphatidylcholine Transfer Protein Interacts with Thioesterase Superfamily Member 2 to Attenuate Insulin Signaling. Science Signaling 2013, 6: ra64. PMID: 23901139, PMCID: PMC3959124, DOI: 10.1126/scisignal.2004111.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsGlucoseHEK293 CellsHomeostasisHumansInhibitory Concentration 50InsulinLiverMechanistic Target of Rapamycin Complex 1MiceMice, TransgenicMultiprotein ComplexesPhospholipid Transfer ProteinsPhosphorylationSignal TransductionThiolester HydrolasesTOR Serine-Threonine KinasesTuberous Sclerosis Complex 2 ProteinTumor Suppressor ProteinsConceptsThioesterase superfamily member 2Insulin receptor substrate 2Phosphatidylcholine transfer proteinTSC1-TSC2 complexGenetic ablationRapamycin complex 1Transfer proteinSteady-state amountsMember 2Hepatic glucose homeostasisPhospholipid-binding proteinProtein exhibitInsulin signalingChemical inhibitionKey effectorsSubstrate 2Mammalian targetDiet-induced diabetesProteinTSC2KnockdownGlucose homeostasisPhospholipid-dependent mechanismsActivationComplexes 1
2005
Molecular mechanism(s) of burn-induced insulin resistance in murine skeletal muscle: Role of IRS phosphorylation
Zhang Q, Carter E, Ma B, White M, Fischman A, Tompkins R. Molecular mechanism(s) of burn-induced insulin resistance in murine skeletal muscle: Role of IRS phosphorylation. Life Sciences 2005, 77: 3068-3077. PMID: 15982669, DOI: 10.1016/j.lfs.2005.02.034.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBurnsDisease Models, AnimalEnzyme ActivationHindlimbInsulin Receptor Substrate ProteinsInsulin ResistanceJNK Mitogen-Activated Protein KinasesMaleMAP Kinase Kinase 4MiceMitogen-Activated Protein Kinase KinasesMuscle, SkeletalPhosphatidylinositol 3-KinasesPhosphoproteinsPhosphorylationProtein Serine-Threonine KinasesProto-Oncogene ProteinsProto-Oncogene Proteins c-aktReceptor, InsulinSignal TransductionConceptsInsulin receptor substrate-1Burn-induced insulin resistanceAkt kinase activityIRS-1 proteinSAPK/JNKSerine 307Kinase activitySkeletal muscleReceptor substrate-1Murine skeletal muscleHind limb skeletal muscleStress kinasesKey proteinsSubstrate-1Biochemical basisPhosphorylationIRS phosphorylationKinase enzymeProteinEnzyme activityJNKLimb skeletal muscleProtein contentInsulin resistanceKinaseInsulin 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 receptorProtein
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
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 phenotypeRegulation
2000
Dysregulation of IRS-proteins causes insulin resistance and diabetes
Aguirre V, White M. Dysregulation of IRS-proteins causes insulin resistance and diabetes. Current Opinion In Endocrinology Diabetes And Obesity 2000, 7: 1-7. DOI: 10.1097/00060793-200002000-00001.Peer-Reviewed Original ResearchIRS proteinsInsulin receptor substrate (IRS) proteinsInsulin/insulin-like growth factorPeripheral insulin resistanceType 2 diabetesInsulin resistanceSubstrate proteinsGenetic approachesCommon type 2 diabetesΒ-cell failureInsulin-like growth factorCompensatory insulin secretionDevelopment of diabetesNormal carbohydrate metabolismEarly-onset formCarbohydrate metabolismGrowth factorInsulin secretionDiabetesInsulin actionImportant insightsDysregulationSecretionProteinResistance
1998
IRS Pleckstrin Homology Domains Bind to Acidic Motifs in Proteins*
Burks D, Wang J, Towery H, Ishibashi O, Lowe D, Riedel H, White M. IRS Pleckstrin Homology Domains Bind to Acidic Motifs in Proteins*. Journal Of Biological Chemistry 1998, 273: 31061-31067. PMID: 9813005, DOI: 10.1074/jbc.273.47.31061.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAmino Acids, DicarboxylicATP-Dependent ProteasesBinding SitesBlood ProteinsHeat-Shock ProteinsInsulin Receptor Substrate ProteinsIntracellular Signaling Peptides and ProteinsLigandsMolecular Sequence DataOligopeptidesPeptide FragmentsPhosphoproteinsProtein BindingRecombinant ProteinsRNA-Binding ProteinsSequence Homology, Amino AcidSerine EndopeptidasesConceptsPH domainAcidic motifIRS-2IRS-1IRS proteinsLon proteaseInsulin-stimulated tyrosine phosphorylationTwo-hybrid systemBinding of nucleolinPleckstrin homologyPhospholipase CgammaMembrane proteinsTyrosine phosphorylationNucleolinPeptide motifsMembrane receptorsInsulin receptorSpecific functionsProteinMotifInsulin actionProteaseSynthetic peptidesBindingDomainThe IRS-signalling system: A network of docking proteins that mediate insulin action
White M. The IRS-signalling system: A network of docking proteins that mediate insulin action. Molecular And Cellular Biochemistry 1998, 182: 3-11. PMID: 9609109, DOI: 10.1023/a:1006806722619.Peer-Reviewed Original ResearchConceptsIRS proteinsTyrosine phosphorylationIntrinsic protein tyrosine kinase activityProtein tyrosine kinase activityInsulin-stimulated tyrosine phosphorylationTyrosine kinase activityDocking proteinKinase activityInsulin actionCellular substratesTyrosine kinaseTransmembrane glycoproteinInsulin receptorBiological responsesPhosphorylationGrowth factorComplete understandingNew moleculesTransductionKinaseType II diabetesProteinEnzymeMoleculesII diabetesThe IRS-signalling system: A network of docking proteins that mediate insulin action
White M. The IRS-signalling system: A network of docking proteins that mediate insulin action. Developments In Molecular And Cellular Biochemistry 1998, 3-11. DOI: 10.1007/978-1-4615-5647-3_1.Peer-Reviewed Original ResearchIRS proteinsTyrosine phosphorylationIntrinsic protein tyrosine kinase activityProtein tyrosine kinase activityInsulin-stimulated tyrosine phosphorylationTyrosine kinase activityDocking proteinKinase activityInsulin actionCellular substratesTyrosine kinaseTransmembrane glycoproteinInsulin receptorBiological responsesPhosphorylationGrowth factorComplete understandingNew moleculesTransductionKinaseType II diabetesProteinEnzymeMoleculesII diabetesThe IRS-Signaling System: A Network of Docking Proteins That Mediate Insulin and Cytokine Action
White M, Yenush L. The IRS-Signaling System: A Network of Docking Proteins That Mediate Insulin and Cytokine Action. Current Topics In Microbiology And Immunology 1998, 228: 179-208. PMID: 9401207, DOI: 10.1007/978-3-642-80481-6_8.Peer-Reviewed Original ResearchConceptsTyrosine phosphorylationSrc homology 2 domainTyrosine autophosphorylation sitesProtein-lipid interactionsAssembly of multicomponentSH2 proteinAutophosphorylation sitesPH domainSpecific membrane receptorsCytosolic substratesReceptor kinaseTyrosine autophosphorylationTransmembrane signalsCellular substratesCytokine receptorsActivity of receptorsMembrane receptorsEarly stepsPhosphorylationProteinKinaseGrowth factorCytokine actionReceptorsCascade
1997
Heterologous Pleckstrin Homology Domains Do Not Couple IRS-1 to the Insulin Receptor*
Burks D, Pons S, Towery H, Smith-Hall J, Myers M, Yenush L, White M. Heterologous Pleckstrin Homology Domains Do Not Couple IRS-1 to the Insulin Receptor*. Journal Of Biological Chemistry 1997, 272: 27716-27721. PMID: 9346913, DOI: 10.1074/jbc.272.44.27716.Peer-Reviewed Original ResearchConceptsIRS-1 proteinPleckstrin homology domainPH domainIRS proteinsInsulin receptorIRS-1Homology domainTyrosine phosphorylationInsulin receptor tyrosine kinaseBeta-adrenergic receptor kinaseReceptor tyrosine kinasesNPEY motifPhospholipase CgammaReceptor kinaseTyrosine kinaseCommon functionProteinKinasePhosphorylationReceptorsDomainCgammaSpectrinMotifHigh levelsThe 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‐signalling system during insulin and cytokine action
Yenush L, White M. The IRS‐signalling system during insulin and cytokine action. BioEssays 1997, 19: 491-500. PMID: 9204766, DOI: 10.1002/bies.950190608.Peer-Reviewed Original ResearchConceptsIRS-1Grb2-binding proteinGeneral cell growthStructure/function relationshipsAnalysis of miceDrosophila proteinIRS proteinsImportant physiological roleSubstrate recognitionDocking moleculeIntracellular substratesIRS-2Physiological roleCell growthFunction relationshipsProteinDependent diabetes mellitusGrowth factorCytokine actionInsulin actionDiabetes mellitusGlucose metabolismReceptor systemGrowth hormoneIntact animals
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 synthesisProteinHDIRP70S6kThe 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 associationComplexesKinaseReceptorsP85Insulin Signal Transduction and the IRS Proteins
Myers M, White M. Insulin Signal Transduction and the IRS Proteins. The Annual Review Of Pharmacology And Toxicology 1996, 36: 615-658. PMID: 8725404, DOI: 10.1146/annurev.pa.36.040196.003151.Peer-Reviewed Original ResearchConceptsIRS proteinsIntracellular tyrosine kinaseBinding of SH2Numerous intracellular signalsTyrosine phosphorylation sitesReceptor-mediated phosphorylationInsulin signal transductionPTB domainCellular physiologyPhosphorylation sitesSignal transductionIntracellular signalsExtracellular domainTyrosine kinaseCytokine receptorsBiochemical eventsInsulin receptorGlucose transportProteinPhosphorylationSignalingGrowth factorSpecific receptorsExciting moleculesPropagation of signalsThe IRS-signalling system in insulin and cytokine action
White M, Marshall C. The IRS-signalling system in insulin and cytokine action. Philosophical Transactions Of The Royal Society B Biological Sciences 1996, 351: 181-189. PMID: 8650265, DOI: 10.1098/rstb.1996.0015.Peer-Reviewed Original ResearchConceptsIRS proteinsSrc homology 2 domainSH2 proteinAutophosphorylation sitesEndocytic pathwayTyrosine residuesIRS-2Cytokine receptorsRecent identificationStoichiometric constraintsMost receptorsIFN-alpha/betaAlpha/betaMultiple receptorsProteinNew insightsCytokine actionIL-13IL-4IGF-1IL-9ReceptorsIFN-gammaGrowth hormoneModular structure