Featured Publications
BRD7 improves glucose homeostasis independent of IRS proteins.
Kim Y, Lee J, Han Y, Tao R, White M, Liu R, Park S. BRD7 improves glucose homeostasis independent of IRS proteins. Journal Of Endocrinology 2023, 258 PMID: 37578842, PMCID: PMC10430774, DOI: 10.1530/joe-23-0119.Peer-Reviewed Original ResearchConceptsGlucose homeostasisKnockout miceAlternative insulinObese miceGlucose homeostasis independentGlucose metabolism parametersContext of obesityBlood glucose levelsMetabolism parametersGlucose levelsGlucose metabolismInsulinMiceIRS proteinsInsulin receptorProtein 7ObesityHomeostasisUpregulationBRD7InvolvementPathwayNovel insightsEuglycemiaFindings
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
Insulin receptor substrate‐2 is expressed in kidney epithelium and up‐regulated in diabetic nephropathy
Hookham M, O'Donovan H, Church R, Mercier‐Zuber A, Luzi L, Curran S, Carew R, Droguett A, Mezzano S, Schubert M, White M, Crean J, Brazil D. Insulin receptor substrate‐2 is expressed in kidney epithelium and up‐regulated in diabetic nephropathy. The FEBS Journal 2013, 280: 3232-3243. PMID: 23617393, PMCID: PMC4022317, DOI: 10.1111/febs.12305.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAnimalsBase SequenceBinding SitesBone Morphogenetic Protein 7Case-Control StudiesCell LineChildDiabetic NephropathiesEpitheliumFemaleGene ExpressionHumansInsulin Receptor Substrate ProteinsKidney TubulesMaleMiceMiddle AgedPhosphorylationProtein Processing, Post-TranslationalSignal TransductionSmad4 ProteinTranscriptional ActivationYoung AdultConceptsDiabetic nephropathyBone morphogenetic protein-7DN patientsInsulin receptor substrateChronic kidney disease severityEnd-stage renal diseaseProgression of DNKidney epitheliumTyrosine/serine phosphorylationHuman kidney proximal tubule epithelial cellsKidney disease severityProximal tubule epithelial cellsKidney proximal tubule epithelial cellsHK-2 cellsRole of insulinInsulin receptor substrate 2Growth factor-β1Tubule epithelial cellsIRS2 transcriptionSDS/PAGEIRS proteinsDN progressionRenal diseaseKidney failureMorphogenetic protein-7
2010
Chapter 331 IRS-Protein Scaffolds and Insulin/IGF Action in Central and Peripheral Tissues
White M. Chapter 331 IRS-Protein Scaffolds and Insulin/IGF Action in Central and Peripheral Tissues. 2010, 2873-2883. DOI: 10.1016/b978-0-12-374145-5.00331-4.Peer-Reviewed Original ResearchInsulin-like growth factor signalsInsulin-like receptorGrowth factor signalsΒ-cell growthIRS proteinsNutrient homeostasisFactor signalsAdapter moleculeSystemic growthInsulin receptorSimilar signalingInsulin targetsRational platformCommon systemic disordersType 2 diabetesCascadePhysiologic roleInsulin actionInsulin resistanceSystemic disordersIGF actionInsulin responseInsulin secretionCardiovascular diseaseDiabetic tissues
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
Role of Insulin Receptor Substrates and Protein Kinase C-ζ in Vascular Permeability Factor/Vascular Endothelial Growth Factor Expression in Pancreatic Cancer Cells*
Neid M, Datta K, Stephan S, Khanna I, Pal S, Shaw L, White M, Mukhopadhyay D. Role of Insulin Receptor Substrates and Protein Kinase C-ζ in Vascular Permeability Factor/Vascular Endothelial Growth Factor Expression in Pancreatic Cancer Cells*. Journal Of Biological Chemistry 2003, 279: 3941-3948. PMID: 14604996, DOI: 10.1074/jbc.m303975200.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaBase SequenceCell Line, TumorDNA, NeoplasmFeedbackGene Expression Regulation, NeoplasticHumansInsulin Receptor Substrate ProteinsIntracellular Signaling Peptides and ProteinsNeovascularization, PathologicPancreatic NeoplasmsPhosphoproteinsProtein Kinase CSignal TransductionSp1 Transcription FactorVascular Endothelial Growth Factor AConceptsVPF/VEGF expressionIRS proteinsIRS-2Negative feedback loopVEGF transcriptionPKC-zetaVascular Permeability Factor/Vascular Endothelial Growth Factor ExpressionPancreatic cancer cellsProtein kinase C zetaCancer cellsInsulin receptor substrate-1IGF-1RReceptor substrate-1Insulin receptor substrateIRS-2 proteinProtein kinase CMajor downstream moleculesInsulin-like growth factor receptorRenal cancer cellsVascular permeability factor/vascular endothelial growth factorIGF-1R signalingGrowth factorRas pathwayGrowth factor receptorC zetaChapter 72 IRS-Protein Scaffolds and Insulin/IGF Action
White M. Chapter 72 IRS-Protein Scaffolds and Insulin/IGF Action. 2003, 409-419. DOI: 10.1016/b978-012124546-7/50433-2.Peer-Reviewed Original ResearchIRS protein familyMultiple biological processesIRS proteinsIL-9 signalingTissue agingBiological processesIRS-2Growth controlPeripheral insulin sensitivityPeripheral insulin actionType 2 diabetesPancreatic p-cellsCell functionIRS2IGF actionIL-4Insulin sensitivityInflammatory responseInsulin actionInsulin secretionIL-7Immune responseFundamental roleTumor growthP cells
2002
SOCS-1 and SOCS-3 Block Insulin Signaling by Ubiquitin-mediated Degradation of IRS1 and IRS2*
Rui L, Yuan M, Frantz D, Shoelson S, White M. SOCS-1 and SOCS-3 Block Insulin Signaling by Ubiquitin-mediated Degradation of IRS1 and IRS2*. Journal Of Biological Chemistry 2002, 277: 42394-42398. PMID: 12228220, DOI: 10.1074/jbc.c200444200.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCarrier ProteinsElonginGlucoseHomeostasisHumansInsulin Receptor Substrate ProteinsInsulin ResistanceIntracellular Signaling Peptides and ProteinsMaleMiceMice, Inbred C57BLPhosphoproteinsProteinsRepressor ProteinsSuppressor of Cytokine Signaling 1 ProteinSuppressor of Cytokine Signaling 3 ProteinSuppressor of Cytokine Signaling ProteinsTranscription FactorsUbiquitinConceptsUbiquitin ligase complexCritical signaling moleculesIRS2 protein levelsDegradation of IRS1Multiple cell typesIRS proteinsSOCS boxSOCS proteinsNutrient homeostasisUbiquitin ligaseSignaling moleculesInflammation-induced insulin resistanceInsulin signalingSOCS-1Expression of SOCS1Cell typesSubsequent degradationHepatic Irs1IRS1IRS2General mechanismUbiquitinationProtein levelsSOCS1MutantsIRS proteins and the common path to diabetes
White M. IRS proteins and the common path to diabetes. AJP Endocrinology And Metabolism 2002, 283: e413-e422. PMID: 12169433, DOI: 10.1152/ajpendo.00514.2001.Peer-Reviewed Original ResearchConceptsInsulin receptor substrate (IRS) proteinsIRS protein functionsProteosome-mediated degradationCommon regulatory pathwayCommon molecular mechanismIntracellular signaling cascadesInsulin/IGF receptorIRS-2 signalingCell surface receptorsIRS proteinsSubstrate proteinsPancreatic beta-cell growthProtein functionGrowth factor actionNutrient sensingSerine phosphorylationRegulatory pathwaysSignaling cascadesIGF-signaling pathwayInsulin resistanceMolecular mechanismsIRS-2Insulin-like growth factor actionIRS-1Broader roleSpecificity 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-1IRS 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
The c-Jun NH2-terminal Kinase Promotes Insulin Resistance during Association with Insulin Receptor Substrate-1 and Phosphorylation of Ser307 *
Davis R, Aguirre V, Uchida T, Yenush L, White M. The c-Jun NH2-terminal Kinase Promotes Insulin Resistance during Association with Insulin Receptor Substrate-1 and Phosphorylation of Ser307 *. Journal Of Biological Chemistry 2000, 275: 9047-9054. PMID: 10722755, DOI: 10.1074/jbc.275.12.9047.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsAnisomycinCHO CellsCricetinaeHumansInsulinInsulin Receptor Substrate ProteinsInsulin ResistanceJNK Mitogen-Activated Protein KinasesMiceMitogen-Activated Protein KinasesMolecular Sequence DataPhosphoproteinsPhosphorylationProtein BindingReceptor, InsulinRecombinant ProteinsSerineSignal TransductionTumor Necrosis Factor-alphaConceptsInsulin-stimulated tyrosine phosphorylationIRS-1Serine 307Tyrosine phosphorylationInsulin receptor substrate-1IRS-1 functionSignal transduction cascadePhosphorylation of Ser307Receptor substrate-1Chinese hamster ovary cellsIRS proteinsActivity of JNKJNK associatesPhosphorylation sitesHamster ovary cellsTransduction cascadeSerine phosphorylationTerminal kinaseSubstrate-1PhosphorylationStrong activatorPromotes Insulin ResistanceJNK phosphorylationOvary cellsJNKDysregulation 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 insightsDysregulationSecretionProteinResistanceDysregulation 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. DOI: 10.1097/00075197-200002000-00001.Peer-Reviewed Original ResearchIRS proteinsPeripheral insulin resistanceInsulin receptor substrate (IRS) proteinsInsulin/insulin-like growth factorType 2 diabetesΒ-cell differentiationInsulin-like growth factorInsulin receptor substrateCompensatory insulin secretionChronic insulin resistanceInsulin resistanceInsulin-signaling pathwayCarbohydrate metabolismInsulin secretionSubstrate proteinsGrowth factorSignal transductionTranscription factorsGenetic approachesCommon type 2 diabetesMolecular basisPancreatic β-cellsReceptor substrateInsulin actionInsulin-signaling system
1999
Differential Modulation of the Tyrosine Phosphorylation State of the Insulin Receptor by IRS (Insulin Receptor Subunit) Proteins
Solow B, Harada S, Goldstein B, Smith J, White M, Jarett L. Differential Modulation of the Tyrosine Phosphorylation State of the Insulin Receptor by IRS (Insulin Receptor Subunit) Proteins. Endocrinology 1999, 13: 1784-1798. PMID: 10517679, DOI: 10.1210/mend.13.10.0361.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAdaptor Proteins, Vesicular TransportAmino Acid MotifsAnimalsInsulinInsulin Receptor Substrate ProteinsMicePhosphatidylinositol 3-KinasesPhosphoproteinsPhosphorylationProtein Tyrosine PhosphatasesProteinsReceptor, InsulinRecombinant ProteinsSequence DeletionShc Signaling Adaptor ProteinsSignal TransductionSrc Homology 2 Domain-Containing, Transforming Protein 1Stem CellsTyrosineVanadatesConceptsInsulin receptor phosphorylationTyrosine kinase activityInsulin receptor tyrosine phosphorylationReceptor tyrosine phosphorylationTyrosine phosphorylationKinase activityIRS-1IRS-2Receptor phosphorylationInsulin receptorTyrosine-phosphorylated IRS-1Insulin stimulationProtein tyrosine phosphatase activityTyrosine phosphorylation stateProtein tyrosine phosphataseReceptor tyrosine kinase activityReceptor kinase activityInsulin receptor kinase activityInsulin receptor subunitsIRS proteinsPervanadate treatmentPhosphorylation stateDownstream eventsInsulin actionTyrosine residues
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 Pleckstrin Homology and Phosphotyrosine Binding Domains of Insulin Receptor Substrate 1 Mediate Inhibition of Apoptosis by Insulin
Yenush L, Zanella C, Uchida T, Bernal D, White M. The Pleckstrin Homology and Phosphotyrosine Binding Domains of Insulin Receptor Substrate 1 Mediate Inhibition of Apoptosis by Insulin. Molecular And Cellular Biology 1998, 18: 6784-6794. PMID: 9774692, PMCID: PMC109262, DOI: 10.1128/mcb.18.11.6784.Peer-Reviewed Original ResearchMeSH KeywordsApoptosisCalcium-Calmodulin-Dependent Protein KinasesCell DivisionCell LineCell SurvivalChromonesDNAInsulinInsulin Receptor Substrate ProteinsInterleukin-3MorpholinesPhosphatidylinositol 3-KinasesPhosphoproteinsPhosphorylationPhosphotyrosineReceptor, InsulinRecombinant Fusion ProteinsRibosomal Protein S6 KinasesConceptsPhosphotyrosine-binding (PTB) domainTyrosine phosphorylation sitesPleckstrin homologyIRS-1 proteinIRS-1Phosphorylation sitesInsulin receptorBinding domainsInsulin receptor substrate (IRS) proteinsReceptor-mediated tyrosine phosphorylationInsulin stimulationChimeric insulin receptorsPKB/AktIL-3 withdrawalIRS proteinsSubstrate proteinsPTB domainKinase cascadeMediated phosphorylationInhibition of apoptosisMyeloid progenitor cellsDiverse biological effectsPhosphatidylinositol 3Protein kinaseTyrosine phosphorylationThe 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