2016
Serine 302 Phosphorylation of Mouse Insulin Receptor Substrate 1 (IRS1) Is Dispensable for Normal Insulin Signaling and Feedback Regulation by Hepatic S6 Kinase*
Copps K, Hançer N, Qiu W, White M. Serine 302 Phosphorylation of Mouse Insulin Receptor Substrate 1 (IRS1) Is Dispensable for Normal Insulin Signaling and Feedback Regulation by Hepatic S6 Kinase*. Journal Of Biological Chemistry 2016, 291: 8602-8617. PMID: 26846849, PMCID: PMC4861431, DOI: 10.1074/jbc.m116.714915.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SubstitutionAnimalsCHO CellsCricetinaeCricetulusGene DeletionGlucose IntoleranceInsulinInsulin Receptor Substrate ProteinsLiverMechanistic Target of Rapamycin Complex 1MiceMice, TransgenicMultiprotein ComplexesMutation, MissensePhosphatidylinositol 3-KinasesPhosphorylationProto-Oncogene Proteins c-aktRibosomal Protein S6 KinasesSerineSignal TransductionTOR Serine-Threonine KinasesTuberous Sclerosis Complex 1 ProteinTumor Suppressor ProteinsConceptsInsulin receptor substrate-1Receptor substrate-1PI3K associationS6 kinaseSubstrate-1Insulin-stimulated Akt activityAkt phosphorylationK associationRapamycin complex 1S6K signalingInsulin-stimulated IRS1 tyrosine phosphorylationSer-302IRS1 tyrosine phosphorylationMTORC1 inhibitor rapamycinRibosomal S6 proteinTsc1 deletionFeedback phosphorylationIntracellular amino acidsInsulin sensitivityTyrosine phosphorylationAlanine mutationsS6 proteinS6KAkt activityInsulin signaling
2013
IRS1Ser307 phosphorylation does not mediate mTORC1-induced insulin resistance
Herrema H, Lee J, Zhou Y, Copps K, White M, Ozcan U. IRS1Ser307 phosphorylation does not mediate mTORC1-induced insulin resistance. Biochemical And Biophysical Research Communications 2013, 443: 689-693. PMID: 24333417, PMCID: PMC3926104, DOI: 10.1016/j.bbrc.2013.12.023.Peer-Reviewed Original ResearchConceptsInsulin resistanceGlucose intoleranceInsulin sensitivityImpaired insulin receptorStress-induced insulin resistanceRapamycin complex 1 (mTORC1) activityPhosphorylation of IRS1Endoplasmic reticulum stressDiabetic miceER stress-induced insulin resistanceMammalian targetIRS1 phosphorylationReticulum stressMiceIntoleranceInsulin receptorVivoSer307Phosphatidylcholine Transfer Protein Interacts with Thioesterase Superfamily Member 2 to Attenuate Insulin Signaling
Ersoy B, Tarun A, D’Aquino K, Hancer N, Ukomadu C, White M, Michel T, Manning B, Cohen D. Phosphatidylcholine Transfer Protein Interacts with Thioesterase Superfamily Member 2 to Attenuate Insulin Signaling. Science Signaling 2013, 6: ra64. PMID: 23901139, PMCID: PMC3959124, DOI: 10.1126/scisignal.2004111.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsGlucoseHEK293 CellsHomeostasisHumansInhibitory Concentration 50InsulinLiverMechanistic Target of Rapamycin Complex 1MiceMice, TransgenicMultiprotein ComplexesPhospholipid Transfer ProteinsPhosphorylationSignal TransductionThiolester HydrolasesTOR Serine-Threonine KinasesTuberous Sclerosis Complex 2 ProteinTumor Suppressor ProteinsConceptsThioesterase superfamily member 2Insulin receptor substrate 2Phosphatidylcholine transfer proteinTSC1-TSC2 complexGenetic ablationRapamycin complex 1Transfer proteinSteady-state amountsMember 2Hepatic glucose homeostasisPhospholipid-binding proteinProtein exhibitInsulin signalingChemical inhibitionKey effectorsSubstrate 2Mammalian targetDiet-induced diabetesProteinTSC2KnockdownGlucose homeostasisPhospholipid-dependent mechanismsActivationComplexes 1
2005
Deletion of Cdkn1b ameliorates hyperglycemia by maintaining compensatory hyperinsulinemia in diabetic mice
Uchida T, Nakamura T, Hashimoto N, Matsuda T, Kotani K, Sakaue H, Kido Y, Hayashi Y, Nakayama K, White M, Kasuga M. Deletion of Cdkn1b ameliorates hyperglycemia by maintaining compensatory hyperinsulinemia in diabetic mice. Nature Medicine 2005, 11: 175-182. PMID: 15685168, DOI: 10.1038/nm1187.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell Cycle ProteinsCell NucleusCyclin-Dependent Kinase Inhibitor p27Diabetes Mellitus, Type 2Disease Models, AnimalEnzyme InhibitorsHyperglycemiaHyperinsulinismInsulin Receptor Substrate ProteinsInsulin-Like Growth Factor IIntracellular Signaling Peptides and ProteinsIslets of LangerhansLeptinMiceMice, KnockoutPhosphoproteinsProtein Serine-Threonine KinasesProto-Oncogene ProteinsProto-Oncogene Proteins c-aktReceptors, Cell SurfaceReceptors, LeptinSignal TransductionTumor Suppressor ProteinsConceptsCyclin-dependent kinasesInsulin receptor substrate 2Cell cycle progressionPancreatic beta cell proliferationPotential new targetsCompensatory hyperinsulinemiaCycle progressionProtein p27Kip1Substrate 2Type 2 diabetes mellitusPancreatic beta cellsP27Kip1Beta-cell failureBeta-cell proliferationType 2 diabetesLong formNew targetsDeletionDiabetes mellitusDiabetic miceIslet massLeptin receptorBeta cellsAnimal modelsMice
2004
Signaling Pathways: The Benefits of Good Communication
Fisher T, White M. Signaling Pathways: The Benefits of Good Communication. Current Biology 2004, 14: r1005-r1007. PMID: 15589136, DOI: 10.1016/j.cub.2004.11.024.Peer-Reviewed Original Research
2002
Stat6 and IRS-2 Cooperate in Interleukin 4 (IL-4)-Induced Proliferation and Differentiation but Are Dispensable for IL-4-Dependent Rescue from Apoptosis
Wurster A, Withers D, Uchida T, White M, Grusby M. Stat6 and IRS-2 Cooperate in Interleukin 4 (IL-4)-Induced Proliferation and Differentiation but Are Dispensable for IL-4-Dependent Rescue from Apoptosis. Molecular And Cellular Biology 2002, 22: 117-126. PMID: 11739727, PMCID: PMC134231, DOI: 10.1128/mcb.22.1.117-126.2002.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisCell Cycle ProteinsCell DifferentiationCell DivisionCell SeparationCells, CulturedCyclin-Dependent Kinase Inhibitor p27Enzyme InhibitorsFlow CytometryInsulin Receptor Substrate ProteinsInterleukin-4Intracellular Signaling Peptides and ProteinsMiceMice, KnockoutPhosphatidylinositol 3-KinasesPhosphoproteinsSignal TransductionSTAT6 Transcription FactorTh2 CellsT-LymphocytesTrans-ActivatorsTumor Suppressor ProteinsConceptsIRS-2Protein tyrosine phosphatase activityProtein tyrosine phosphatase inhibitorTyrosine phosphatase activityTyrosine phosphatase inhibitorWild-type cellsIL-4 signal transductionIRS-2 expressionIL-4-induced proliferationCDK inhibitor p27Kip1Antiapoptotic effectPrimary T cellsPhosphatase inhibitorCytoplasmic tailSignal transductionDifferentiation eventsCooperative regulationGene expressionAntiapoptotic signalsCell developmentAntiapoptotic activityInterleukin-4 receptorPhosphatase activityPrimary lymphocytesSTAT6