2016
Down-regulation of Insulin Receptor Substrate 1 during Hyperglycemia Induces Vascular Smooth Muscle Cell Dedifferentiation*
Xi G, Wai C, White M, Clemmons D. Down-regulation of Insulin Receptor Substrate 1 during Hyperglycemia Induces Vascular Smooth Muscle Cell Dedifferentiation*. Journal Of Biological Chemistry 2016, 292: 2009-2020. PMID: 28003360, PMCID: PMC5290970, DOI: 10.1074/jbc.m116.758987.Peer-Reviewed Original ResearchConceptsInsulin receptor substrate-1Receptor substrate-1IRS-1Differentiated stateSubstrate-1Aberrant signalingMetabolic stressVascular smooth muscle cell dedifferentiationIGF-I stimulationIRS-1 expressionVascular smooth muscle cell migrationScaffold proteinSHPS-1Transcription factorsSmooth muscle cell dedifferentiationSmooth muscle cell migrationMuscle cell dedifferentiationMuscle cell migrationReceptor signalsVSMC dedifferentiationCell migrationInsulin-like growth factor ICell dedifferentiationMajor risk factorDevelopment of atherosclerosis
2009
Targeted Disruption of ROCK1 Causes Insulin Resistance in Vivo *
Lee D, Shi J, Jeoung N, Kim M, Zabolotny J, Lee S, White M, Wei L, Kim Y. Targeted Disruption of ROCK1 Causes Insulin Resistance in Vivo *. Journal Of Biological Chemistry 2009, 284: 11776-11780. PMID: 19276091, PMCID: PMC2673246, DOI: 10.1074/jbc.c900014200.Peer-Reviewed Original ResearchMeSH KeywordsAdiposityAnimalsDiabetes Mellitus, Type 2GlucoseGTPase-Activating ProteinsInsulinInsulin Receptor Substrate ProteinsInsulin ResistanceMiceMice, KnockoutObesityPhosphatidylinositol 3-KinasesPhosphorylationProto-Oncogene Proteins c-aktRho-Associated KinasesRibosomal Protein S6 KinasesSignal TransductionConceptsIRS-1Skeletal muscleWhole-body glucose homeostasisInsulin resistanceBody glucose homeostasisCultured cell linesPhosphorylation of AktPhospho-tyrosinesGlucose homeostasisROCK1-deficient miceSerine phosphorylationNovel regulatorTyrosine phosphorylationS6KRho kinase isoformsInsulin sensitivityPhysiological roleGene ablationAbility of insulinInsulin receptorTargeted disruptionPhosphorylationNormal glucose homeostasisGlucose-induced insulin secretionROCK1
2008
Muscle-Specific IRS-1 Ser→Ala Transgenic Mice Are Protected From Fat-Induced Insulin Resistance in Skeletal Muscle
Morino K, Neschen S, Bilz S, Sono S, Tsirigotis D, Reznick RM, Moore I, Nagai Y, Samuel V, Sebastian D, White M, Philbrick W, Shulman GI. Muscle-Specific IRS-1 Ser→Ala Transgenic Mice Are Protected From Fat-Induced Insulin Resistance in Skeletal Muscle. Diabetes 2008, 57: 2644-2651. PMID: 18633112, PMCID: PMC2551673, DOI: 10.2337/db06-0454.Peer-Reviewed Original ResearchMeSH KeywordsAlanineAmino Acid SubstitutionAnimalsBlotting, WesternDietary FatsFemaleGlucose Clamp TechniqueGlucose Tolerance TestImmunoprecipitationInsulinInsulin Receptor Substrate ProteinsInsulin ResistanceMaleMiceMice, Inbred C57BLMice, TransgenicMuscle, SkeletalPhosphorylationSerineTriglyceridesConceptsSerine phosphorylationIRS-1IRS-1-associated phosphatidylinositolSkeletal muscleInsulin-stimulated IRS-1-associated phosphatidylinositolWild-type transgenic miceFat-induced insulin resistanceInsulin receptor substrateTransgenic miceReceptor substrateInsulin signalingAkt phosphorylationPhosphorylationCellular mechanismsCritical roleGlucose uptakeHigh-fat feedingInsulin resistanceMuscle glucose uptakeInsulin actionVivoSerInsulin-stimulated muscle glucose uptakeImportant rolePhosphatidylinositol
2007
Insulin receptor substrate 1 (IRS‐1) plays a unique role in normal epidermal physiology
Sadagurski M, Nofech‐Mozes S, Weingarten G, White M, Kadowaki T, Wertheimer E. Insulin receptor substrate 1 (IRS‐1) plays a unique role in normal epidermal physiology. Journal Of Cellular Physiology 2007, 213: 519-527. PMID: 17508357, DOI: 10.1002/jcp.21131.Peer-Reviewed Original ResearchConceptsNull miceIRS-1IRS-1 null miceIRS-2Skin physiologySkin cellsNormal epidermal physiologyInsulin receptor substrate-1Primary skin cellsSkin differentiationIRS-2 proteinReceptor substrate-1Skin epidermal cellsInsulin actionAdvanced stageExpression of K1Histological analysisNull skinSkin sectionsInsulin receptor substrate (IRS) proteinsEpidermal physiologyMiceSkin keratinocytesMarked decreaseEffects of inactivation
2006
Suppression of Insulin Receptor Substrate 1 (IRS-1) Promotes Mammary Tumor Metastasis
Ma Z, Gibson S, Byrne M, Zhang J, White M, Shaw L. Suppression of Insulin Receptor Substrate 1 (IRS-1) Promotes Mammary Tumor Metastasis. Molecular And Cellular Biology 2006, 26: 9338-9351. PMID: 17030605, PMCID: PMC1698550, DOI: 10.1128/mcb.01032-06.Peer-Reviewed Original ResearchConceptsIRS-1Insulin receptor substrate (IRS) proteinsInsulin receptor substrate-1Wild-type levelsMetastasis suppressor functionReceptor substrate-1Cell surface receptorsBreast cancerSubstrate proteinsCytoplasmic adaptorAkt/mTOR activityMammary tumor metastasisSignificant homologySerine phosphorylationDistinct functionsSubstrate-1Mammary tumorsIRS-2MTOR activitySuppressor functionMetastatic mammary tumorsTumor cellsIR-1Surface receptorsBreast cancer metastasis
2004
Mammalian target of rapamycin regulates IRS-1 serine 307 phosphorylation
Carlson C, White M, Rondinone C. Mammalian target of rapamycin regulates IRS-1 serine 307 phosphorylation. Biochemical And Biophysical Research Communications 2004, 316: 533-539. PMID: 15020250, DOI: 10.1016/j.bbrc.2004.02.082.Peer-Reviewed Original ResearchConceptsSerine 307 phosphorylationSerine 307Rapamycin-sensitive mannerInsulin receptor substrateRole of mTORAmino acid stimulationActivation of mTORPhosphatase PP2AKinase mTOROkadaic acidReceptor substrateInsulin signalingIRS-1MTOR activityPhosphorylationMammalian targetMTORCytosolic fractionRapamycinPP2AAcid stimulationPKBInhibitorsSignalingJNK
2003
Nutrient-dependent and Insulin-stimulated Phosphorylation of Insulin Receptor Substrate-1 on Serine 302 Correlates with Increased Insulin Signaling*
Giraud J, Leshan R, Lee Y, White M. Nutrient-dependent and Insulin-stimulated Phosphorylation of Insulin Receptor Substrate-1 on Serine 302 Correlates with Increased Insulin Signaling*. Journal Of Biological Chemistry 2003, 279: 3447-3454. PMID: 14623899, DOI: 10.1074/jbc.m308631200.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAmino AcidsAndrostadienesAnimalsBlotting, WesternBromodeoxyuridineCell DivisionCell LineCHO CellsCricetinaeCulture Media, Serum-FreeDose-Response Relationship, DrugEnzyme InhibitorsGlucoseGlycogen Synthase Kinase 3Glycogen Synthase Kinase 3 betaInsulinInsulin Receptor Substrate ProteinsJNK Mitogen-Activated Protein KinasesMiceMitogen-Activated Protein KinasesMolecular Sequence DataMutagenesis, Site-DirectedMutationPhosphoproteinsPhosphorylationPoint MutationPrecipitin TestsRatsSerineSignal TransductionSirolimusTime FactorsWortmanninConceptsInsulin/IGFIRS-1Insulin-stimulated signal transductionInsulin receptor substrate IRS-1Ser/Thr phosphorylationSequence-specific polyclonal antibodiesInsulin-stimulated tyrosine phosphorylationInsulin receptor substrate-1Synthase kinase-3beta phosphorylationSubstrate IRS-1IRS-1-mediated signalingRibosomal S6 proteinC-Jun kinaseInsulin-stimulated phosphorylationReceptor substrate-1IGF-I stimulationThr phosphorylationKinase associatesP85 bindingPhosphorylated residuesSignal transductionInsulin-stimulated AktTyrosine phosphorylationS6 proteinNutrient availability
2002
Mechanism by Which Fatty Acids Inhibit Insulin Activation of Insulin Receptor Substrate-1 (IRS-1)-associated Phosphatidylinositol 3-Kinase Activity in Muscle*
Yu C, Chen Y, Cline GW, Zhang D, Zong H, Wang Y, Bergeron R, Kim JK, Cushman SW, Cooney GJ, Atcheson B, White MF, Kraegen EW, Shulman GI. Mechanism by Which Fatty Acids Inhibit Insulin Activation of Insulin Receptor Substrate-1 (IRS-1)-associated Phosphatidylinositol 3-Kinase Activity in Muscle*. Journal Of Biological Chemistry 2002, 277: 50230-50236. PMID: 12006582, DOI: 10.1074/jbc.m200958200.Peer-Reviewed Original ResearchConceptsIRS-1 tyrosine phosphorylationInsulin receptor substrate-1PI3-kinase activityReceptor substrate-1IRS-1Tyrosine phosphorylationSubstrate-1Insulin activationIRS-1-associated PI3-kinase activityInsulin-stimulated IRS-1 tyrosine phosphorylationInsulin-stimulated glucose transport activityProtein kinase CGlucose transport activityFatty acidsLipid infusionFatty acyl-CoAsDAG concentrationKinase CTransport activityPKC-thetaPhosphorylationIntracellular ceramideAcyl-CoAsTime-dependent fashionPhosphatidylinositolIRS 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
Role of Allelic Variants Gly972Arg of IRS-1 and Gly1057Asp of IRS-2 in Moderate-to-Severe Insulin Resistance of Women With Polycystic Ovary Syndrome
El Mkadem S, Lautier C, Macari F, Molinari N, Lefèbvre P, Renard E, Gris J, Cros G, Daurès J, Bringer J, White M, Grigorescu F. Role of Allelic Variants Gly972Arg of IRS-1 and Gly1057Asp of IRS-2 in Moderate-to-Severe Insulin Resistance of Women With Polycystic Ovary Syndrome. Diabetes 2001, 50: 2164-2168. PMID: 11522686, DOI: 10.2337/diabetes.50.9.2164.Peer-Reviewed Original ResearchConceptsPolycystic ovary syndromeInsulin resistanceIRS-1 variantOvary syndromeInsulin-resistant patientsIRS-2Severe insulin resistanceIRS-1IRS-2 geneControl subjectsPlasma glucoseInsulin receptor substrateWild-type variantMultivariate modelInsulin receptorNovel mutationsDirect sequencingGene dosage effectReceptor substrateSyndromeVariable degreesFunctional impactWomenPolymorphic allelesGly972ArgRegulation 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-1Association of Insulin Receptor Substrate 1 (IRS-1) Y895 with Grb-2 Mediates the Insulin Signaling Involved in IRS-1-Deficient Brown Adipocyte Mitogenesis
Valverde A, Mur C, Pons S, Alvarez A, White M, Kahn C, Benito M. Association of Insulin Receptor Substrate 1 (IRS-1) Y895 with Grb-2 Mediates the Insulin Signaling Involved in IRS-1-Deficient Brown Adipocyte Mitogenesis. Molecular And Cellular Biology 2001, 21: 2269-2280. PMID: 11259577, PMCID: PMC86861, DOI: 10.1128/mcb.21.7.2269-2280.2001.Peer-Reviewed Original ResearchConceptsMitogen-activated protein kinaseGrb-2Tyrosine phosphorylationIRS-1Brown adipocytesMAPK activationBrown adipocyte cell lineDNA synthesisActivation of MAPKWild-type IRS-1IRS-2 tyrosine phosphorylationShc tyrosine phosphorylationProtein kinase kinaseInhibition of phosphatidylinositolWild-type cell linesIRS-1 deficiencyInsulin-induced IRS-1Cell linesInsulin receptor substrate-1 (IRS-1) knockout miceAdipocyte cell lineG2/M phaseKinase kinaseMutant cellsProtein kinaseCell cycleIRS 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 phenotypeRegulationInsulin/IGF-1 and TNF-α stimulate phosphorylation of IRS-1 at inhibitory Ser307 via distinct pathways
Rui L, Aguirre V, Kim J, Shulman G, Lee A, Corbould A, Dunaif A, White M. Insulin/IGF-1 and TNF-α stimulate phosphorylation of IRS-1 at inhibitory Ser307 via distinct pathways. Journal Of Clinical Investigation 2001, 107: 181-189. PMID: 11160134, PMCID: PMC199174, DOI: 10.1172/jci10934.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnisomycinCHO CellsCricetinaeInsulinInsulin AntagonistsInsulin ResistanceInsulin-Like Growth Factor IMAP Kinase Kinase 1Mitogen-Activated Protein Kinase KinasesPhosphatidylinositol 3-KinasesPhosphorylationProtein Serine-Threonine KinasesReceptor, InsulinSerineSignal TransductionTumor Necrosis Factor-alphaTyrosineConceptsPhosphorylation of Ser307IRS-1Serine/threonine phosphorylationTNF-alpha-stimulated phosphorylationInsulin-stimulated tyrosine phosphorylationRelevant phosphorylation sitesDistinct kinase pathwaysInsulin/IGFInsulin-stimulated phosphorylationThreonine phosphorylationStimulates PhosphorylationPhosphorylation sitesJun kinaseTyrosine phosphorylationKinase pathwaySer307PhosphorylationCultured cellsDistinct pathwaysHeterologous inhibitionPolyclonal antibodiesPreadipocytesPathwayAdipocytesCells
2000
Contrasting Effects of IRS-1 Versus IRS-2 Gene Disruption on Carbohydrate and Lipid Metabolism in Vivo *
Previs S, Withers D, Ren J, White M, Shulman G. Contrasting Effects of IRS-1 Versus IRS-2 Gene Disruption on Carbohydrate and Lipid Metabolism in Vivo *. Journal Of Biological Chemistry 2000, 275: 38990-38994. PMID: 10995761, DOI: 10.1074/jbc.m006490200.Peer-Reviewed Original ResearchMeSH KeywordsAdipose TissueAnimalsCarbohydrate MetabolismFatty Acids, NonesterifiedFood DeprivationGas Chromatography-Mass SpectrometryGlucoseGlycerolInsulinInsulin Receptor Substrate ProteinsIntracellular Signaling Peptides and ProteinsLipid MetabolismLiverMaleMiceMusclesMutationPhenotypePhosphoproteinsRadioimmunoassayTime FactorsConceptsLipid metabolismInsulin resistanceIRS-2Glucose utilizationPlasma free fatty acid concentrationsWhole-body glucose utilizationGlycerol turnoverFree fatty acid concentrationsMarked insulin resistancePeripheral glucose metabolismPeripheral glucose utilizationHyperinsulinemic-euglycemic clampEndogenous glucose productionIRS-1Effect of insulinHepatic glycogen synthesisWT miceFatty acid concentrationsInsulin receptor substrateGlucose metabolismFasted miceAdipose tissueReduced suppressionGlucose productionMiceThe 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 cellsJNKIRS-4 Mediates Protein Kinase B Signaling during Insulin Stimulation without Promoting Antiapoptosis
Uchida T, Myers M, White M. IRS-4 Mediates Protein Kinase B Signaling during Insulin Stimulation without Promoting Antiapoptosis. Molecular And Cellular Biology 2000, 20: 126-138. PMID: 10594015, PMCID: PMC85068, DOI: 10.1128/mcb.20.1.126-138.2000.Peer-Reviewed Original ResearchConceptsPKB/AktProtein kinase BIRS-1IRS-2IRS-4Insulin stimulationGrb-2Bad phosphorylationInsulin-stimulated mitogen-activated protein kinase activityInsulin receptor substrate (IRS) proteinsProtein kinase B signalingMitogen-activated protein kinase activityProtein kinase activityHuman insulin receptorPhosphorylation of BadKinase B signalingSubstrate proteinsMyeloid progenitor cellsApoptosis of cellsKinase activityKinase BPhosphatidylinositolInsulin receptorInterleukin-3Phosphorylation
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
Differential Regulation of Insulin Receptor Substrate-2 and Mitogen-Activated Protein Kinase Tyrosine Phosphorylation by Phosphatidylinositol 3-Kinase Inhibitors in SH-SY5Y Human Neuroblastoma Cells*This work was supported by NIH Grants R29-NS-32843 and R01-NS-36778, grants from the American Diabetes Association and Juvenile Diabetes Foundation (to E.L.F.), and a grant from the Millie Schembechler Adrenal Research Fund of the University of Michigan Comprehensive Cancer Center (to E.L.F. and P.S.L.).
Kim B, Leventhal P, White M, Feldman E. Differential Regulation of Insulin Receptor Substrate-2 and Mitogen-Activated Protein Kinase Tyrosine Phosphorylation by Phosphatidylinositol 3-Kinase Inhibitors in SH-SY5Y Human Neuroblastoma Cells*This work was supported by NIH Grants R29-NS-32843 and R01-NS-36778, grants from the American Diabetes Association and Juvenile Diabetes Foundation (to E.L.F.), and a grant from the Millie Schembechler Adrenal Research Fund of the University of Michigan Comprehensive Cancer Center (to E.L.F. and P.S.L.). Endocrinology 1998, 139: 4881-4889. PMID: 9832424, DOI: 10.1210/endo.139.12.6348.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAdaptor Proteins, Vesicular TransportCalcium-Calmodulin-Dependent Protein KinasesElectrophoresis, Polyacrylamide GelEnzyme InhibitorsGRB2 Adaptor ProteinHumansInsulin Receptor Substrate ProteinsInsulin-Like Growth Factor IIntracellular Signaling Peptides and ProteinsIsoenzymesMitogen-Activated Protein Kinase 1NeuritesNeuroblastomaPhosphatidylinositol 3-KinasesPhosphoinositide-3 Kinase InhibitorsPhosphoproteinsPhosphorylationProteinsShc Signaling Adaptor ProteinsSrc Homology 2 Domain-Containing, Transforming Protein 1Tumor Cells, CulturedTyrosineConceptsInsulin receptor substrate 2IRS-2 tyrosine phosphorylationMitogen-activated protein kinase activationTyrosine phosphorylationProtein kinase activationKinase activationSerine/threonine phosphorylationSubstrate 2Association of Grb2Neurite outgrowthSH-SY5Y human neuroblastomaThreonine phosphorylationNegative regulationSH-SY5Y human neuroblastoma cellsIRS-1Grb2Nervous system growthDifferential regulationPhosphorylationHuman neuroblastoma cellsNeuronal cellsPhosphatidylinositolPI 3Concentration-dependent mannerInsulin-like growth factor I