Featured Publications
Mechanism of Insulin Action
White M. Mechanism of Insulin Action. 2024, 111-127. DOI: 10.1002/9781119697473.ch9.Peer-Reviewed Original ResearchReceptor tyrosine kinasesTyrosine kinaseGrowth factor signalingSecrete sufficient insulinDysregulated insulin signalingPancreatic beta cellsMuscle insulin resistanceEnvironmental signalsSignal transductionInsulin signalingMuscle-specific deletionSystemic insulin actionSystemic insulin resistanceAdequate insulin responseFactor signalingInsulin-like growth factor signalingPlasma membraneInsulin resistanceInsulin receptorLigand bindingBeta cellsMetabolic stressChronic insulin resistanceGlucose transportTransphosphorylation
2018
Receptor Tyrosine Kinases and the Insulin Signaling System
White M. Receptor Tyrosine Kinases and the Insulin Signaling System. Endocrinology 2018, 121-155. DOI: 10.1007/978-3-319-44675-2_7.Peer-Reviewed Original ResearchProtein tyrosine kinasesTyrosine kinaseExtracellular ligand-binding domainLarge multigene familyRTK family membersInsulin Signaling SystemCell-cell interactionsLigand-binding domainReceptor tyrosine kinasesSystemic nutrient homeostasisPolypeptide growth factorsAspects of metabolismMultigene familyHuman genomeNutrient homeostasisPlasma membraneIntracellular signalsMetabolic regulationSignaling systemInsulin receptorBroader roleHeterologous regulationCell proliferationKinaseGrowth factor
2017
Receptor Tyrosine Kinases and the Insulin Signaling System
White M. Receptor Tyrosine Kinases and the Insulin Signaling System. Endocrinology 2017, 1-34. DOI: 10.1007/978-3-319-27318-1_7-1.Peer-Reviewed Original ResearchProtein tyrosine kinasesTyrosine kinaseExtracellular ligand-binding domainLarge multigene familyRTK family membersInsulin Signaling SystemCell-cell interactionsLigand-binding domainReceptor tyrosine kinasesSystemic nutrient homeostasisPolypeptide growth factorsAspects of metabolismMultigene familyHuman genomeNutrient homeostasisPlasma membraneIntracellular signalsMetabolic regulationSignaling systemInsulin receptorBroader roleHeterologous regulationCell proliferationKinaseGrowth factor
2016
Mechanism of Insulin Action
White M. Mechanism of Insulin Action. 2016, 114-132. DOI: 10.1002/9781118924853.ch8.Peer-Reviewed Original ResearchInsulin-like signalingGenome-wide association studiesInsulin-like peptidesClassical insulin target tissuesInsulin-like growth factor 2Receptor tyrosine kinasesSimilar receptor tyrosine kinasesEnvironmental signalsHuman genomeInsulin target tissuesGenetic lociPancreatic β-cellsInsulin signalTyrosine kinaseAssociation studiesRelease of nutrientsConflicting signalsGrowth factor 2IGF signalingAnimal growthFactor 1Factor 2Insulin-like growth factor-1Β-cellsGenes
2014
Insulin and Metabolic Stress Stimulate Multisite Serine/Threonine Phosphorylation of Insulin Receptor Substrate 1 and Inhibit Tyrosine Phosphorylation*
Hançer N, Qiu W, Cherella C, Li Y, Copps K, White M. Insulin and Metabolic Stress Stimulate Multisite Serine/Threonine Phosphorylation of Insulin Receptor Substrate 1 and Inhibit Tyrosine Phosphorylation*. Journal Of Biological Chemistry 2014, 289: 12467-12484. PMID: 24652289, PMCID: PMC4007441, DOI: 10.1074/jbc.m114.554162.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnisomycinAntigens, CDBlotting, WesternCHO CellsCricetinaeCricetulusEnzyme InhibitorsHumansHypoglycemic AgentsInsulinInsulin Receptor Substrate ProteinsPhosphatidylinositol 3-KinasesPhosphoinositide-3 Kinase InhibitorsPhosphorylationProtein Serine-Threonine KinasesProto-Oncogene Proteins c-aktRatsReceptor, InsulinRibosomal Protein S6 Kinases, 70-kDaSerineSignal TransductionThapsigarginThreonineTOR Serine-Threonine KinasesTunicamycinTyrosineConceptsTyrosine phosphorylationPhospho-specific monoclonal antibodiesSerine/threonine phosphorylationInsulin receptor tyrosine kinasePI3KInsulin receptor substrate-1Insulin-stimulated cellsHuman insulin receptorIRS1 tyrosine phosphorylationReceptor substrate-1Metabolic stressReceptor tyrosine kinasesThreonine phosphorylationThreonine residuesS6 kinasePI3K inhibitionSubstrate-1Mechanistic targetTyrosine kinaseInsulin stimulationMEK pathwayKey substrateInsulin receptorPresence of inhibitorsCHO cells
2013
Nerve Growth Factor Receptor TrkA, a New Receptor in Insulin Signaling Pathway in PC12 Cells*
Geetha T, Rege S, Mathews S, Meakin S, White M, Babu J. Nerve Growth Factor Receptor TrkA, a New Receptor in Insulin Signaling Pathway in PC12 Cells*. Journal Of Biological Chemistry 2013, 288: 23807-23813. PMID: 23749991, PMCID: PMC3745327, DOI: 10.1074/jbc.m112.436279.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid MotifsAmino Acid SequenceAnimalsEnzyme ActivationGlucoseHumansInsulinInsulin Receptor Substrate ProteinsMitogen-Activated Protein Kinase 7Molecular Sequence DataNerve Growth FactorPC12 CellsPhosphorylationPhosphotyrosineProtein BindingProto-Oncogene Proteins c-aktRatsReceptor, InsulinReceptor, trkASignal TransductionConceptsInsulin receptor substrate-1Insulin receptorPC12 cellsTrkA kinase domainTransmembrane receptor tyrosine kinaseKinase-inactive mutantInsulin Signaling PathwayReceptor substrate-1Nerve growth factor receptor TrkAReceptor tyrosine kinasesNerve growth factorActivation of AktNPXY motifKinase domainTyrosine phosphorylationSubstrate-1Regulatory loopTyrosine kinaseSignaling pathwaysGrowth factorNew receptorsReceptor TrkACellsPathwayTrkA
2012
Regulation of insulin sensitivity by serine/threonine phosphorylation of insulin receptor substrate proteins IRS1 and IRS2
Copps K, White M. Regulation of insulin sensitivity by serine/threonine phosphorylation of insulin receptor substrate proteins IRS1 and IRS2. Diabetologia 2012, 55: 2565-2582. PMID: 22869320, PMCID: PMC4011499, DOI: 10.1007/s00125-012-2644-8.Peer-Reviewed Original ResearchConceptsInsulin receptor substrateT phosphorylationReceptor substrateSerine/threonine residuesSerine/threonine phosphorylationInsulin receptor tyrosine kinaseInsulin-stimulated kinasesReceptor tyrosine kinasesThreonine phosphorylationThreonine residuesNegative regulationTyrosine kinasePhosphorylationCultured cellsKinaseMetabolic diseasesIRS2IRS1Hormonal controlKey targetAltered patternTail regionComplex mechanismsRegulationDysregulation
2011
Mechanisms of Insulin Action
White M, White M. Mechanisms of Insulin Action. 2011, 19-38. DOI: 10.1007/978-1-4614-1028-7_2.Peer-Reviewed Original ResearchInsulin-like growth factor 2Receptor tyrosine kinasesTyrosine kinaseInsulin-like signalingInsulin-like peptidesG protein-coupled receptorsInsulin-like growth factor-1Caenorhabditis elegansEnvironmental signalsHuman genomeFruit flyRelease of nutrientsGrowth factor 2Factor 1Factor 2Somatic growthKinaseLower animalsGrowth factor-1Common mechanismSimilar peptidesInsulin actionWide arrayMetabolismMetazoans
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
2002
Defective insulin secretion in pancreatic β cells lacking type 1 IGF receptor
Xuan S, Kitamura T, Nakae J, Politi K, Kido Y, Fisher P, Morroni M, Cinti S, White M, Herrera P, Accili D, Efstratiadis A. Defective insulin secretion in pancreatic β cells lacking type 1 IGF receptor. Journal Of Clinical Investigation 2002, 110: 1011-1019. PMID: 12370279, PMCID: PMC151144, DOI: 10.1172/jci15276.Peer-Reviewed Original ResearchConceptsType 1 IGF receptorBeta-cell massDefective insulin secretionInsulin secretionIGF receptorInsulin releaseInadequate compensatory increaseGlucose-dependent insulin releaseBeta-cell proliferationAge-dependent impairmentPancreatic β-cellsGlucose toleranceDecrease of glucoseBeta cellsType 2Compensatory increaseCell massΒ-cellsReceptor tyrosine kinasesSecretionCell proliferationAntiapoptotic roleReceptorsTyrosine kinaseConditional mutagenesisSpecificity 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-4
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-1
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 signalsThe 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 diabetes
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 levels
1996
Cross-talk between the insulin and angiotensin signaling systems.
Velloso L, Folli F, Sun X, White M, Saad M, Kahn C. Cross-talk between the insulin and angiotensin signaling systems. Proceedings Of The National Academy Of Sciences Of The United States Of America 1996, 93: 12490-12495. PMID: 8901609, PMCID: PMC38019, DOI: 10.1073/pnas.93.22.12490.Peer-Reviewed Original ResearchMeSH KeywordsAngiotensin IIAnimalsElectrophoresis, Polyacrylamide GelInsulinInsulin Receptor Substrate ProteinsIntracellular Signaling Peptides and ProteinsJanus Kinase 1Janus Kinase 2Janus Kinase 3MalePhosphatidylinositol 3-KinasesPhosphoproteinsPhosphorylationPhosphotransferases (Alcohol Group Acceptor)Protein-Tyrosine KinasesProto-Oncogene ProteinsRatsRats, WistarSignal TransductionTyrosineConceptsAngiotensin IIInjection of ANGIIEffect of AIIIRS-1/IRSAT1 receptor antagonistInsulin receptorRenal functionAT1 receptorInsulin resistanceReceptor antagonistCardiovascular diseaseAII stimulationAcute inhibitionIRS phosphorylationTyrosine phosphorylationReceptorsIRS-2Insulin-stimulated PIIRS-1G proteinsJAK2 tyrosine kinaseImportant regulatorInsulinRapid tyrosine phosphorylationTyrosine kinaseTumor Necrosis Factor (TNF)-α Inhibits Insulin Signaling through Stimulation of the p55 TNF Receptor and Activation of Sphingomyelinase*
Peraldi P, Hotamisligil G, Buurman W, White M, Spiegelman B. Tumor Necrosis Factor (TNF)-α Inhibits Insulin Signaling through Stimulation of the p55 TNF Receptor and Activation of Sphingomyelinase*. Journal Of Biological Chemistry 1996, 271: 13018-13022. PMID: 8662983, DOI: 10.1074/jbc.271.22.13018.Peer-Reviewed Original ResearchMeSH Keywords3T3 CellsAdipocytesAnimalsAntigens, CDCell LineCeramidesEnzyme ActivationHumansInsulinInsulin Receptor Substrate ProteinsMicePhosphoproteinsPhosphorylationReceptor, InsulinReceptors, Tumor Necrosis FactorReceptors, Tumor Necrosis Factor, Type ISignal TransductionSphingomyelin PhosphodiesteraseTumor Necrosis Factor-alphaTyrosineConceptsInsulin receptor substrate-1Myeloid 32D cellsInsulin receptorP55 TNF receptorP75 TNF receptorTyrosine phosphorylationInhibits InsulinIRS-2Insulin-dependent tyrosine phosphorylationTNF receptorIRS-1 tyrosine phosphorylationTNF-alphaIR tyrosine kinaseReceptor substrate-1Tyrosine kinase activityNecrosis factorActivation of sphingomyelinaseSerine phosphorylationBiological functionsKinase activitySubstrate-1Tyrosine kinaseExogenous sphingomyelinaseMurine TNF-alphaTumor necrosis factorInsulin 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 signals
1991
The Juxtamembrane Regions of the Epidermal Growth Factor Receptor and gpl85 erbB-2 Determine the Specificity of Signal Transduction
Segatto O, Lonardo F, Wexler D, Fazioli F, Pierce J, Bottaro D, White M, Di Fiore P. The Juxtamembrane Regions of the Epidermal Growth Factor Receptor and gpl85 erbB-2 Determine the Specificity of Signal Transduction. Molecular And Cellular Biology 1991, 11: 3191-3202. DOI: 10.1128/mcb.11.6.3191-3202.1991.Peer-Reviewed Original ResearchEpidermal growth factor receptorSignal transductionSpecificity of substrate recognitionErbB-2Specificity of signal transductionAmino-terminal halfDeletion of residuesMitogenic signaling pathwaysMitogenic signal transductionEGFR kinaseGrowth factor receptorSubstrate recognitionTyrosine kinase domainJuxtamembrane regionKinase domainStructural homologyKinase propertiesFactor receptorMutation analysisSignaling pathwayTyrosine kinaseChimeric moleculesKinaseTyrosineTransduction