Featured Publications
The P300 acetyltransferase inhibitor C646 promotes membrane translocation of insulin receptor protein substrate and interaction with the insulin receptor
Peng J, Ramatchandirin B, Wang Y, Pearah A, Namachivayam K, Wolf R, Steele K, MohanKumar K, Yu L, Guo S, White M, Maheshwari A, He L. The P300 acetyltransferase inhibitor C646 promotes membrane translocation of insulin receptor protein substrate and interaction with the insulin receptor. Journal Of Biological Chemistry 2022, 298: 101621. PMID: 35074429, PMCID: PMC8850660, DOI: 10.1016/j.jbc.2022.101621.Peer-Reviewed Original ResearchConceptsAbsence of insulinP300 acetyltransferase activityTyrosine kinase activityAcetyltransferase activityInsulin receptorObese patientsTyrosine phosphorylationRole of acetylationInsulinNormal functionMembrane translocationSubsequent activationC646PatientsLiver hepatocytesProtein substratesInhibitionReceptorsMolecular mechanismsHepatocytesPhosphorylationBeta subunitKinase activityObesityUnique effects
2013
Chronic activation of a designer Gq-coupled receptor improves β cell function
Jain S, de Azua I, Lu H, White M, Guettier J, Wess J. Chronic activation of a designer Gq-coupled receptor improves β cell function. Journal Of Clinical Investigation 2013, 123: 1750-1762. PMID: 23478411, PMCID: PMC3613926, DOI: 10.1172/jci66432.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell Line, TumorCell ProliferationClozapineDiabetes Mellitus, ExperimentalDrug Evaluation, PreclinicalFemaleGene ExpressionGTP-Binding Protein alpha Subunits, Gq-G11Hypoglycemic AgentsInsulin Receptor Substrate ProteinsInsulin-Secreting CellsMaleMAP Kinase Signaling SystemMiceMice, Inbred C57BLMice, TransgenicMolecular Targeted TherapyMuscarinic AgonistsProtein EngineeringReceptor, Muscarinic M3Receptors, G-Protein-CoupledRecombinant ProteinsConceptsΒ-cell functionΒ-cellsCell functionPancreatic β-cell functionStreptozotocin-induced diabetesBeneficial metabolic effectsTreatment of T2D.High-fat dietType 2 diabetesNovel antidiabetic drugsType G proteinsClasses of receptorsChronic stimulationMetabolic deficitsAntidiabetic drugsMetabolic effectsChronic activationGlucose homeostasisTherapeutic strategiesCell pathwaysEnhanced expressionReceptorsNumerous receptorsCellular effectsDiabetes
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 mutagenesis
1999
Irs-2 coordinates Igf-1 receptor-mediated β-cell development and peripheral insulin signalling
Withers D, Burks D, Towery H, Altamuro S, Flint C, White M. Irs-2 coordinates Igf-1 receptor-mediated β-cell development and peripheral insulin signalling. Nature Genetics 1999, 23: 32-40. PMID: 10471495, DOI: 10.1038/12631.Peer-Reviewed Original ResearchMeSH KeywordsAge FactorsAnimalsApoptosisBlood GlucoseBody WeightFemaleGene Expression Regulation, DevelopmentalGlucose Tolerance TestInsulinInsulin Receptor Substrate ProteinsIntracellular Signaling Peptides and ProteinsIslets of LangerhansLiverMaleMiceMice, KnockoutMuscle, SkeletalPancreasPhosphoproteinsReceptor, IGF Type 1Signal TransductionTime FactorsConceptsIGF-1 receptorΒ-cell developmentIGF-1Glucose homeostasisΒ-cellsPeripheral insulin resistancePeripheral target tissuesEffect of insulinPancreatic β-cellsPeripheral insulinInsulin resistanceInsulin receptor substratePost-natal growthGlucose metabolismNull allelesTarget tissuesInsulinMiceReceptor substrateIR-1Carbohydrate metabolismReceptorsSurvivalCell growthPleiotropic effects
1998
The 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 levelsTyr624 and Tyr628 in Insulin Receptor Substrate-2 Mediate Its Association with the Insulin Receptor*
Sawka-Verhelle D, Baron V, Mothe I, Filloux C, White M, Van Obberghen E. Tyr624 and Tyr628 in Insulin Receptor Substrate-2 Mediate Its Association with the Insulin Receptor*. Journal Of Biological Chemistry 1997, 272: 16414-16420. PMID: 9195949, DOI: 10.1074/jbc.272.26.16414.Peer-Reviewed Original ResearchConceptsInsulin receptorIRS-2Tyrosine residuesPleckstrin homology domainPeptide competition studiesInsulin receptor substrateAmino acids 591Homology domainReceptor substrateBinding domainsRegulatory loopIRS-1Novel mechanismPosition 624ResiduesCompetition studiesReceptorsDomainIts AssociationPhosphotyrosinePhosphorylationBindsBindingRegionInteraction
1996
Growth Hormone, Interferon-γ, and Leukemia Inhibitory Factor Utilize Insulin Receptor Substrate-2 in Intracellular Signaling*
Argetsinger L, Norstedt G, Billestrup N, White M, Carter-Su C. Growth Hormone, Interferon-γ, and Leukemia Inhibitory Factor Utilize Insulin Receptor Substrate-2 in Intracellular Signaling*. Journal Of Biological Chemistry 1996, 271: 29415-29421. PMID: 8910607, DOI: 10.1074/jbc.271.46.29415.Peer-Reviewed Original ResearchMeSH Keywords3T3 CellsAnimalsCHO CellsCricetinaeGrowth InhibitorsHuman Growth HormoneHumansInsulin Receptor Substrate ProteinsInterferon-gammaInterleukin-6Intracellular Signaling Peptides and ProteinsLeukemia Inhibitory FactorLymphokinesMicePhosphatidylinositol 3-KinasesPhosphoproteinsPhosphorylationPhosphotransferases (Alcohol Group Acceptor)Signal TransductionTyrosineConceptsInsulin receptor substrate 2Tyrosyl phosphorylationLeukemia inhibitory factorProtein tyrosine phosphatase SHP2Substrate 2JAK2 associationPhosphatase SHP2Regulatory subunitJAK kinasesMaximal phosphorylationTyrosine phosphorylationTyrosine residuesIntracellular signalingPhosphorylationMultiple membersGH receptorInhibitory factorCytokine familyGrowth hormoneReceptorsSHP2KinasePhosphatidylinositolSubstantial signalCross-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 kinaseThe 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 associationComplexesKinaseReceptorsP85The 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