2017
Correction for Long et al., “Insulin Receptor Substrates Irs1 and Irs2 Coordinate Skeletal Muscle Growth and Metabolism via the Akt and AMPK Pathways”
Long Y, Cheng Z, Copps K, White M. Correction for Long et al., “Insulin Receptor Substrates Irs1 and Irs2 Coordinate Skeletal Muscle Growth and Metabolism via the Akt and AMPK Pathways”. Molecular And Cellular Biology 2017, 37: e00232-17. PMID: 28710120, PMCID: PMC5514452, DOI: 10.1128/mcb.00232-17.Peer-Reviewed Original Research
2013
Insulin receptor substrate signaling suppresses neonatal autophagy in the heart
Riehle C, Wende A, Sena S, Pires K, Pereira R, Zhu Y, Bugger H, Frank D, Bevins J, Chen D, Perry C, Dong X, Valdez S, Rech M, Sheng X, Weimer B, Gottlieb R, White M, Abel E. Insulin receptor substrate signaling suppresses neonatal autophagy in the heart. Journal Of Clinical Investigation 2013, 123: 5319-5333. PMID: 24177427, PMCID: PMC3859408, DOI: 10.1172/jci71171.Peer-Reviewed Original ResearchMeSH KeywordsAmino AcidsAnimalsApoptosisApoptosis Regulatory ProteinsAutophagyBeclin-1Cardiomyopathy, DilatedFetal HeartHeartHeart FailureInsulinInsulin Receptor Substrate ProteinsInsulin-Like Growth Factor IMiceMitochondria, HeartMyocytes, CardiacOxidative PhosphorylationPhosphorylationProtein Processing, Post-TranslationalReceptor, IGF Type 1Signal TransductionTOR Serine-Threonine KinasesConceptsInsulin receptor substrateInduction of autophagyActivation of mTORIGF-1R signalingPostnatal cardiac developmentUnrestrained autophagyCardiomyocyte-specific deletionGenetic suppressionCardiac developmentReceptor substrateIGF-1 receptorEssential adaptationProsurvival signalingAutophagic fluxAutophagy suppressionAutophagyMitochondrial dysfunctionMammalian heartPhysiological suppressionNeonatal starvationAutophagic activationSignalingIRS1IRS2Insulin actionMyocardial Loss of IRS1 and IRS2 Causes Heart Failure and Is Controlled by p38α MAPK During Insulin Resistance
Qi Y, Xu Z, Zhu Q, Thomas C, Kumar R, Feng H, Dostal D, White M, Baker K, Guo S. Myocardial Loss of IRS1 and IRS2 Causes Heart Failure and Is Controlled by p38α MAPK During Insulin Resistance. Diabetes 2013, 62: 3887-3900. PMID: 24159000, PMCID: PMC3806607, DOI: 10.2337/db13-0095.Peer-Reviewed Original ResearchConceptsIRS2 proteinGene expressionType 2 diabetesEnergy metabolism gene expressionInsulin resistanceMetabolic gene expressionBox class ODouble knockout miceHeart failureActivation of p38Chronic insulin exposureActivation of p38αMetabolism gene expressionProtein kinaseRole of IRS1Cellular metabolismMolecular mechanismsInsulin receptorNeonatal rat ventricular cardiomyocytesP38α MAPKCause heart failureCellular dysfunctionIRS1Myocardial insulin resistanceClass O
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-86SignalingIRS1Insulin Receptor Substrates Irs1 and Irs2 Coordinate Skeletal Muscle Growth and Metabolism via the Akt and AMPK Pathways
Long Y, Cheng Z, Copps K, White M. Insulin Receptor Substrates Irs1 and Irs2 Coordinate Skeletal Muscle Growth and Metabolism via the Akt and AMPK Pathways. Molecular And Cellular Biology 2011, 31: 430-441. PMID: 21135130, PMCID: PMC3028618, DOI: 10.1128/mcb.00983-10.Peer-Reviewed Original ResearchMeSH KeywordsAMP-Activated Protein KinasesAnimalsBody CompositionBody WeightEnzyme ActivationForkhead Transcription FactorsGlucoseHomeostasisIn Vitro TechniquesInsulinInsulin Receptor Substrate ProteinsLactic AcidMiceMice, KnockoutModels, BiologicalMuscle, SkeletalMyocardiumOrgan SizeOrgan SpecificityProto-Oncogene Proteins c-aktSignal TransductionUp-RegulationConceptsSkeletal muscle growthMdKO miceMuscle growthElevated AMP/ATP ratioInsulin-receptor substrate IRS1AMP/ATP ratioSkeletal muscleInsulin receptor substrateMuscle creatine kinaseSubstrates IRS1Insulin-stimulated glucose uptakeProtein kinaseNutrient availabilityReceptor substrateCarboxylase phosphorylationFatty acid oxidationAMPK pathwayMetabolic homeostasisATP ratioIRS1Impaired growthKinaseAmino acid releaseSkeletal muscle massAtrogene expression
2010
Irs1 Serine 307 Promotes Insulin Sensitivity in Mice
Copps K, Hancer N, Opare-Ado L, Qiu W, Walsh C, White M. Irs1 Serine 307 Promotes Insulin Sensitivity in Mice. Cell Metabolism 2010, 11: 84-92. PMID: 20074531, PMCID: PMC3314336, DOI: 10.1016/j.cmet.2009.11.003.Peer-Reviewed Original Research
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
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
2005
Irs1 and Irs2 signaling is essential for hepatic glucose homeostasis and systemic growth
Dong X, Park S, Lin X, Copps K, Yi X, White M. Irs1 and Irs2 signaling is essential for hepatic glucose homeostasis and systemic growth. Journal Of Clinical Investigation 2005, 116: 101-114. PMID: 16374520, PMCID: PMC1319221, DOI: 10.1172/jci25735.Peer-Reviewed Original ResearchConceptsSystemic growthHundreds of genesInsulin receptor substrateHepatic nutrient homeostasisHepatic glucose homeostasisHeterologous pathwaysNutrient homeostasisReceptor substrateGene expressionGSK3beta phosphorylationReceptor signalsHepatic gene expressionLKO miceInsulin receptorGlucose homeostasisIRS2IRS1Hepatic genesHepatic insulin receptorAkt-FoxO1 pathwayHomeostasisGenesHepatic glycogen storesLKO liversPathway
2002
SOCS-1 and SOCS-3 Block Insulin Signaling by Ubiquitin-mediated Degradation of IRS1 and IRS2*
Rui L, Yuan M, Frantz D, Shoelson S, White M. SOCS-1 and SOCS-3 Block Insulin Signaling by Ubiquitin-mediated Degradation of IRS1 and IRS2*. Journal Of Biological Chemistry 2002, 277: 42394-42398. PMID: 12228220, DOI: 10.1074/jbc.c200444200.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCarrier ProteinsElonginGlucoseHomeostasisHumansInsulin Receptor Substrate ProteinsInsulin ResistanceIntracellular Signaling Peptides and ProteinsMaleMiceMice, Inbred C57BLPhosphoproteinsProteinsRepressor ProteinsSuppressor of Cytokine Signaling 1 ProteinSuppressor of Cytokine Signaling 3 ProteinSuppressor of Cytokine Signaling ProteinsTranscription FactorsUbiquitinConceptsUbiquitin ligase complexCritical signaling moleculesIRS2 protein levelsDegradation of IRS1Multiple cell typesIRS proteinsSOCS boxSOCS proteinsNutrient homeostasisUbiquitin ligaseSignaling moleculesInflammation-induced insulin resistanceInsulin signalingSOCS-1Expression of SOCS1Cell typesSubsequent degradationHepatic Irs1IRS1IRS2General mechanismUbiquitinationProtein levelsSOCS1Mutants