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
2019
Phosphorylation of Forkhead Protein FoxO1 at S253 Regulates Glucose Homeostasis in Mice
Zhang K, Guo X, Yan H, Wu Y, Pan Q, Shen J, Li X, Chen Y, Li L, Qi Y, Xu Z, Xie W, Zhang W, Threadgill D, He L, Villarreal D, Sun Y, White M, Zheng H, Guo S. Phosphorylation of Forkhead Protein FoxO1 at S253 Regulates Glucose Homeostasis in Mice. Endocrinology 2019, 160: 1333-1347. PMID: 30951171, PMCID: PMC6482038, DOI: 10.1210/en.2018-00853.Peer-Reviewed Original ResearchConceptsKey phosphorylation sitesForkhead protein FoxO1Protein kinase BTranscription factor forkhead box O1Factor forkhead box O1FOXO1 nuclear localizationMultiple physiological functionsMouse Foxo1Forkhead box O1Pancreatic plasticityPhosphorylation sitesHuman FOXO1Nuclear localizationTarget genesMolecular basisS253Kinase BFoxO1 activityPhysiological functionsGlucose homeostasisBox O1Pancreatic β-cell functionFOXO1PhosphorylationHepatic glucose production
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
Inhibition of Insulin Signaling in Endothelial Cells by Protein Kinase C-induced Phosphorylation of p85 Subunit of Phosphatidylinositol 3-Kinase (PI3K)*
Maeno Y, Li Q, Park K, Rask-Madsen C, Gao B, Matsumoto M, Liu Y, Wu I, White M, Feener E, King G. Inhibition of Insulin Signaling in Endothelial Cells by Protein Kinase C-induced Phosphorylation of p85 Subunit of Phosphatidylinositol 3-Kinase (PI3K)*. Journal Of Biological Chemistry 2011, 287: 4518-4530. PMID: 22158866, PMCID: PMC3281670, DOI: 10.1074/jbc.m111.286591.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCattleCells, CulturedClass Ia Phosphatidylinositol 3-KinaseEndothelial CellsEnzyme ActivationInsulinInsulin Receptor Substrate ProteinsMetabolic DiseasesNitric Oxide Synthase Type IIIPhosphorylationProtein Kinase CProto-Oncogene Proteins c-aktSignal TransductionVascular Endothelial Growth Factor AConceptsP85/PI3KPI3KPKC activationInsulin receptor substrateProtein kinase C activationEndothelial nitric oxide synthaseProtein kinase CAkt/endothelial nitric oxide synthaseKinase C activationPI3K/Akt pathwayP85 subunitDeletion mutantsGeneral activatorTyrosine phosphorylationReceptor substrateEndothelial cellsInsulin signalingInsulin activationKinase CAkt pathwayPhosphorylationC activationThr-86SignalingIRS1
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 rolePhosphatidylinositolStructural and biochemical characterization of the KRLB region in insulin receptor substrate-2
Wu J, Tseng Y, Xu C, Neubert T, White M, Hubbard S. Structural and biochemical characterization of the KRLB region in insulin receptor substrate-2. Nature Structural & Molecular Biology 2008, 15: 251-258. PMID: 18278056, DOI: 10.1038/nsmb.1388.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsCHO CellsCricetinaeCricetulusCrystallography, X-RayHumansInsulin Receptor Substrate ProteinsIntracellular Signaling Peptides and ProteinsMiceModels, MolecularMolecular Sequence DataMutationPhosphoproteinsPhosphorylationPhosphotyrosineProtein BindingProtein Structure, TertiaryProtein-Tyrosine KinasesReceptor, IGF Type 1Structure-Activity RelationshipSubstrate SpecificityConceptsInsulin receptorPleckstrin homology domainCrucial adaptor proteinTwo-hybrid studiesInsulin receptor kinaseKinase active siteInsulin receptor substrate 2C-terminal regionTyrosine kinase domainPrevious yeastThreonine phosphorylationHomology domainAdaptor proteinReceptor kinaseKinase domainTyrosine phosphorylationBiochemical characterizationRegion functionsSubstrate 2Binding regionsPhosphorylationKinase inhibitionFactor 1IRS2Insulin-like growth factor-1
2007
Phosphorylation of Irs1 at SER-522 Inhibits Insulin Signaling
Giraud J, Haas M, Feener E, Copps K, Dong X, Dunn S, White M. Phosphorylation of Irs1 at SER-522 Inhibits Insulin Signaling. Endocrinology 2007, 21: 2294-2302. PMID: 17579213, DOI: 10.1210/me.2007-0159.Peer-Reviewed Original ResearchConceptsTyrosine phosphorylationInsulin-stimulated tyrosine phosphorylationInsulin-stimulated IRS1 tyrosine phosphorylationIRS1 tyrosine phosphorylationInsulin-stimulated phosphorylationPhosphorylation of IRS1Threonine residuesMultisite phosphorylationPhosphorylation sitesPhosphoserine antibodyInhibits InsulinL6 myoblastsPhosphorylationCultured cellsIRS1Akt expressionPhosphatidylinositolFunctional effectsMass spectrometryPD98059WortmanninMyoblastsMyotubesRNASerine
2005
Phosphatase and Tensin Homolog Regulation of Islet Growth and Glucose Homeostasis*
Kushner J, Simpson L, Wartschow L, Guo S, Rankin M, Parsons R, White M. Phosphatase and Tensin Homolog Regulation of Islet Growth and Glucose Homeostasis*. Journal Of Biological Chemistry 2005, 280: 39388-39393. PMID: 16170201, DOI: 10.1074/jbc.m504155200.Peer-Reviewed Original ResearchConceptsInsulin/insulin-like growth factorWild typeIrs2 branchBeta-cell growthInsulin-like growth factorPhosphatase PTENGrowth factorFoxO1 phosphorylationBeta-cell massPTEN expressionAktPTENCascadeSmall isletsGlucose homeostasisInsulin productionGrowthIslet growthSufficient insulinPhosphatidylinositolTolerancePhosphorylationMiceSignalingHomeostasisMolecular mechanism(s) of burn-induced insulin resistance in murine skeletal muscle: Role of IRS phosphorylation
Zhang Q, Carter E, Ma B, White M, Fischman A, Tompkins R. Molecular mechanism(s) of burn-induced insulin resistance in murine skeletal muscle: Role of IRS phosphorylation. Life Sciences 2005, 77: 3068-3077. PMID: 15982669, DOI: 10.1016/j.lfs.2005.02.034.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBurnsDisease Models, AnimalEnzyme ActivationHindlimbInsulin Receptor Substrate ProteinsInsulin ResistanceJNK Mitogen-Activated Protein KinasesMaleMAP Kinase Kinase 4MiceMitogen-Activated Protein Kinase KinasesMuscle, SkeletalPhosphatidylinositol 3-KinasesPhosphoproteinsPhosphorylationProtein Serine-Threonine KinasesProto-Oncogene ProteinsProto-Oncogene Proteins c-aktReceptor, InsulinSignal TransductionConceptsInsulin receptor substrate-1Burn-induced insulin resistanceAkt kinase activityIRS-1 proteinSAPK/JNKSerine 307Kinase activitySkeletal muscleReceptor substrate-1Murine skeletal muscleHind limb skeletal muscleStress kinasesKey proteinsSubstrate-1Biochemical basisPhosphorylationIRS phosphorylationKinase enzymeProteinEnzyme activityJNKLimb skeletal muscleProtein contentInsulin resistanceKinase
2004
Disruption of the SH2-B Gene Causes Age-Dependent Insulin Resistance and Glucose Intolerance
Duan C, Yang H, White M, Rui L. Disruption of the SH2-B Gene Causes Age-Dependent Insulin Resistance and Glucose Intolerance. Molecular And Cellular Biology 2004, 24: 7435-7443. PMID: 15314154, PMCID: PMC506995, DOI: 10.1128/mcb.24.17.7435-7443.2004.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAdipose TissueAgingAnimalsBlood GlucoseCarrier ProteinsCell LineDietary FatsGlucose IntoleranceHomeostasisHumansInsulinInsulin Receptor Substrate ProteinsInsulin ResistanceIntracellular Signaling Peptides and ProteinsIslets of LangerhansLiverMaleMiceMice, Inbred StrainsMice, KnockoutMitogen-Activated Protein KinasesMuscle, SkeletalPhosphatidylinositol 3-KinasesPhosphoproteinsProtein Serine-Threonine KinasesProto-Oncogene ProteinsProto-Oncogene Proteins c-aktReceptor, InsulinSignal TransductionConceptsSrc homology 2Insulin receptor substrate-1Insulin receptor activationInsulin receptorTyrosine phosphorylationSH2 domain-dependent mannerPleckstrin homology domain-containing adaptor proteinDomain-containing adaptor proteinDomain-dependent mannerReceptor substrate-1Skeletal muscleSH2 domainHomology 2Adaptor proteinReceptor activationSubstrate-1Physiological roleCultured cellsGlucose homeostasisERK1/2 pathwayDependent insulin resistancePhysiological enhancerSystemic deletionPhosphorylationIRS2Mammalian 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
Insulin Receptor Substrate-2 Deficiency Impairs Brain Growth and Promotes Tau Phosphorylation
Schubert M, Brazil D, Burks D, Kushner J, Ye J, Flint C, Farhang-Fallah J, Dikkes P, Warot X, Rio C, Corfas G, White M. Insulin Receptor Substrate-2 Deficiency Impairs Brain Growth and Promotes Tau Phosphorylation. Journal Of Neuroscience 2003, 23: 7084-7092. PMID: 12904469, PMCID: PMC6740672, DOI: 10.1523/jneurosci.23-18-07084.2003.Peer-Reviewed Original ResearchMeSH KeywordsAge FactorsAnimalsApoptosisBody WeightBrainCell CountCell DivisionCell SurvivalCells, CulturedCerebellumCrosses, GeneticEnzyme InhibitorsHeterozygoteIn Situ Nick-End LabelingInsulin Receptor Substrate ProteinsIntracellular Signaling Peptides and ProteinsMiceMice, KnockoutNeuronsOrgan SizePhosphoproteinsPhosphorylationReceptor, IGF Type 1Signal TransductionTau ProteinsConceptsMolecular linkInsulin receptor substrate (IRS) proteinsBrain growthNeurodegenerative diseasesPancreatic beta-cell functionPeripheral insulin actionSubstrate proteinsBeta-cell functionTyrosine phosphorylationLike growth factorIrs2 branchInsulin resistanceTau phosphorylationIRS2 geneNeuronal proliferationInsulin actionMouse brainInsulin-IGFGrowth factorPhosphorylationIRS2DiabetesBody growthDiseaseMice
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 fashionPhosphatidylinositolc-Jun N-terminal Kinase (JNK) Mediates Feedback Inhibition of the Insulin Signaling Cascade*
Lee Y, Giraud J, Davis R, White M. c-Jun N-terminal Kinase (JNK) Mediates Feedback Inhibition of the Insulin Signaling Cascade*. Journal Of Biological Chemistry 2002, 278: 2896-2902. PMID: 12417588, DOI: 10.1074/jbc.m208359200.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsBinding SitesCell LineConsensus SequenceCulture Media, ConditionedHumansInsulinInsulin Receptor Substrate ProteinsJNK Mitogen-Activated Protein KinasesMiceMice, KnockoutMitogen-Activated Protein Kinase 8Mitogen-Activated Protein Kinase 9Mitogen-Activated Protein KinasesMolecular Sequence DataPhosphoproteinsPhosphorylationRatsSignal TransductionTransfectionConceptsC-Jun N-terminal kinaseN-terminal kinaseDirect bindingInsulin-stimulated tyrosine phosphorylationInsulin receptor substrate-1Interaction of JNKInsulin Signaling CascadeReceptor substrate-1Mouse embryo fibroblastsActivation of JNKFeedback inhibitionNegative feedback regulatorPhosphorylation of IRS1Cellular proteinsCell-permeable peptideTyrosine phosphorylationInsulin signalSignaling cascadesIRS1 proteinJNK activitySubstrate-1Insulin stimulationEmbryo fibroblastsPhosphorylationAkt phosphorylationInsulin Signaling After Exercise in Insulin Receptor Substrate-2-Deficient Mice
Howlett K, Sakamoto K, Hirshman M, Aschenbach W, Dow M, White M, Goodyear L. Insulin Signaling After Exercise in Insulin Receptor Substrate-2-Deficient Mice. Diabetes 2002, 51: 479-483. PMID: 11812758, DOI: 10.2337/diabetes.51.2.479.Peer-Reviewed Original ResearchConceptsPhosphotyrosine-associated phosphatidylinositolIRS-2 tyrosine phosphorylationIRS-2 signalingInsulin receptor substrate-2-deficient (IRS2(-/-)) miceWild-type miceIRS-2-deficient miceEnhanced insulin actionWT miceTyrosine phosphorylationTreadmill exerciseInsulin receptor substrateInsulin actionMiceImmediate periodSkeletal muscleInsulin-stimulated responsesInsulin signalingMarked increaseReceptor substrateExerciseInsulinPresent studySignalingPhosphorylation
2001
Phosphorylation of Ser307 in Insulin Receptor Substrate-1 Blocks Interactions with the Insulin Receptor and Inhibits Insulin Action*
Aguirre V, Werner E, Giraud J, Lee Y, Shoelson S, White M. Phosphorylation of Ser307 in Insulin Receptor Substrate-1 Blocks Interactions with the Insulin Receptor and Inhibits Insulin Action*. Journal Of Biological Chemistry 2001, 277: 1531-1537. PMID: 11606564, DOI: 10.1074/jbc.m101521200.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnisomycinAnti-Bacterial AgentsCell LineHumansInsulinInsulin Receptor Substrate ProteinsMitogen-Activated Protein Kinase 8Mitogen-Activated Protein KinasesPhosphatidylinositol 3-KinasesPhosphoproteinsPhosphorylationRatsReceptor, InsulinRecombinant Fusion ProteinsSignal TransductionTumor Necrosis Factor-alphaTwo-Hybrid System TechniquesConceptsInsulin receptor substrate-1Phosphotyrosine-binding (PTB) domainInsulin receptorPotential phosphorylation sitesPhosphorylation of Ser307Stress-activated kinasesInsulin-stimulated kinasesReceptor substrate-1Insulin signal transductionPTB domainMAPK cascadePhosphorylation sitesMyeloid progenitor cellsSignal transductionSerine residuesCatalytic domainSerine phosphorylationDomain functionsSubstrate-1Insulin stimulationCell backgroundPhosphorylationProgenitor cellsGeneral mechanismMechanism of inhibitionInsulin/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
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 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