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
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 cells
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 cellsJNKTyrosine Dephosphorylation and Deactivation of Insulin Receptor Substrate-1 by Protein-tyrosine Phosphatase 1B POSSIBLE FACILITATION BY THE FORMATION OF A TERNARY COMPLEX WITH THE GRB2 ADAPTOR PROTEIN*
Goldstein B, Bittner-Kowalczyk A, White M, Harbeck M. Tyrosine Dephosphorylation and Deactivation of Insulin Receptor Substrate-1 by Protein-tyrosine Phosphatase 1B POSSIBLE FACILITATION BY THE FORMATION OF A TERNARY COMPLEX WITH THE GRB2 ADAPTOR PROTEIN*. Journal Of Biological Chemistry 2000, 275: 4283-4289. PMID: 10660596, DOI: 10.1074/jbc.275.6.4283.Peer-Reviewed Original ResearchConceptsInsulin receptor substrate-1Receptor substrate-1Tyrosine dephosphorylationAdaptor proteinSubstrate-1Tyrosine-phosphorylated IRS-1Src homology 2 domainSteady-state tyrosine phosphorylationAdaptor protein Grb2Grb2 adaptor proteinStable protein complexesProtein tyrosine phosphataseNovel molecular interactionInsulin signal transductionMolecular interactionsProtein Grb2Protein complexesP85 subunitSHP-2Overlay blotsP-nitrophenyl phosphateSignal transductionTyrosine phosphorylationPhosphorylation stateInactive PTP1B
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 residuesCharacterization of selective resistance to insulin signaling in the vasculature of obese Zucker (fa/fa) rats
Jiang Z, Lin Y, Clemont A, Feener E, Hein K, Igarashi M, Yamauchi T, White M, King G. Characterization of selective resistance to insulin signaling in the vasculature of obese Zucker (fa/fa) rats. Journal Of Clinical Investigation 1999, 104: 447-457. PMID: 10449437, PMCID: PMC408521, DOI: 10.1172/jci5971.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAortaCalcium-Calmodulin-Dependent Protein KinasesIn Vitro TechniquesInsulinInsulin Receptor Substrate ProteinsInsulin ResistanceIntracellular Signaling Peptides and ProteinsLiverMaleMicrocirculationObesityPhosphatidylinositol 3-KinasesPhosphoproteinsPhosphorylationRatsRats, ZuckerReceptor, InsulinRecombinant ProteinsSignal TransductionTyrosineConceptsObese ratsLean ratsObese ZuckerIRS-2-associated PIIndependent risk factorProtein levelsEuglycemic clamp studiesInsulin-resistant statesObese Zucker ratsSelective resistanceTyrosine phosphorylationVascular tissueInsulin resistanceInsulin infusionRisk factorsCardiovascular diseaseClamp studiesZucker ratsReceptor beta subunitAortaRatsInsulinInsulin receptor beta subunitERK 1/2Vivo studies
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 peptidesBindingDomain
1997
Interaction of p59fynwith Interferon-Activated Jak Kinases
Uddin S, Sher D, Alsayed Y, Pons S, Colamonici O, Fish E, White M, Platanias L. Interaction of p59fynwith Interferon-Activated Jak Kinases. Biochemical And Biophysical Research Communications 1997, 235: 83-88. PMID: 9196040, DOI: 10.1006/bbrc.1997.6741.Peer-Reviewed Original ResearchAntibodies, MonoclonalBlotting, WesternGlutathione TransferaseHumansInterferon Type IInterferon-gammaJanus Kinase 1Janus Kinase 2PhosphotyrosineProteinsProtein-Tyrosine KinasesProto-Oncogene MasProto-Oncogene ProteinsProto-Oncogene Proteins c-cblProto-Oncogene Proteins c-fynRecombinant Fusion ProteinsRecombinant ProteinsSignal TransductionSrc Homology DomainsTumor Cells, CulturedTYK2 KinaseUbiquitin-Protein Ligases
1996
The Pleckstrin Homology Domain Is the Principle Link between the Insulin Receptor and IRS-1*
Yenush L, Makati K, Smith-Hall J, Ishibashi O, Myers M, White M. The Pleckstrin Homology Domain Is the Principle Link between the Insulin Receptor and IRS-1*. Journal Of Biological Chemistry 1996, 271: 24300-24306. PMID: 8798677, DOI: 10.1074/jbc.271.39.24300.Peer-Reviewed Original ResearchAmino Acid SequenceBinding SitesBlood ProteinsCell LineInsulin Receptor Substrate ProteinsMolecular Sequence DataPhosphatidylinositol 3-KinasesPhosphoproteinsPhosphotransferases (Alcohol Group Acceptor)PhosphotyrosineProtein BindingProtein Serine-Threonine KinasesReceptor, InsulinRecombinant ProteinsRibosomal Protein S6 KinasesYMXM 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 synthesisProteinHDIRP70S6kInsulin Receptor Substrate-2 Binds to the Insulin Receptor through Its Phosphotyrosine-binding Domain and through a Newly Identified Domain Comprising Amino Acids 591–786 (∗)
Sawka-Verhelle D, Tartare-Deckert S, White M, Van Obberghen E. Insulin Receptor Substrate-2 Binds to the Insulin Receptor through Its Phosphotyrosine-binding Domain and through a Newly Identified Domain Comprising Amino Acids 591–786 (∗). Journal Of Biological Chemistry 1996, 271: 5980-5983. PMID: 8626379, DOI: 10.1074/jbc.271.11.5980.Peer-Reviewed Original ResearchConceptsTwo-hybrid systemIRS-2IRS-1Insulin receptorNPEY motifNPXY motifPhosphotyrosine-binding (PTB) domainPleckstrin homology domainTyrosine phosphorylation sitesActivated insulin receptorInsulin receptor kinaseIRS-2 phosphorylationReceptor tyrosine kinase activityTyrosine kinase activityAmino acids 591IRS proteinsHomology domainPhosphorylation sitesInteraction domainReceptor kinaseCytoplasmic portionBinding domainsKinase activityRegulatory loopNH2 terminus