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
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
Insulin receptor substrate proteins and diabetes
Lee Y, White M. Insulin receptor substrate proteins and diabetes. Archives Of Pharmacal Research 2004, 27: 361-370. PMID: 15180298, DOI: 10.1007/bf02980074.Peer-Reviewed Original ResearchConceptsInsulin receptor substrate (IRS) proteinsSubstrate proteinsPancreatic β-cell growthInsulin/IGFIntracellular signaling cascadesReceptor tyrosine kinasesΒ-cell growthCell surface receptorsIRS proteinsGrowth factor actionProtein signalingSerine phosphorylationSignaling cascadesInsulin resistanceTyrosine kinaseInsulin-like growth factor actionIrs2 branchCell growthSurface receptorsFactor actionPeripheral insulin responsePeripheral insulin resistanceIRS2ProteinImportant mechanism
2002
IRS 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 role
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 inhibition
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 cellsJNK
1999
Endothelin-1 modulates insulin signaling through phosphatidylinositol 3-kinase pathway in vascular smooth muscle cells.
Jiang Z, Zhou Q, Chatterjee A, Feener E, Myers M, White M, King G. Endothelin-1 modulates insulin signaling through phosphatidylinositol 3-kinase pathway in vascular smooth muscle cells. Diabetes 1999, 48: 1120-1130. PMID: 10331419, DOI: 10.2337/diabetes.48.5.1120.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsEndothelin Receptor AntagonistsEndothelin-1Enzyme InhibitorsGTP-Binding ProteinsHumansInsulinInsulin Receptor Substrate ProteinsIntracellular Signaling Peptides and ProteinsMaleMuscle, Smooth, VascularPeptides, CyclicPertussis ToxinPhosphatidylinositol 3-KinasesPhosphoinositide-3 Kinase InhibitorsPhosphoproteinsPhosphoserineProtein Kinase CRatsRats, ZuckerSignal TransductionTetradecanoylphorbol AcetateVirulence Factors, BordetellaConceptsInsulin-stimulated phosphatidylinositolProtein kinase CIRS-2P85 subunitSerine phosphorylationSmooth muscle cellsInsulin receptor beta subunitInsulin-induced phosphatidylinositolInsulin receptor substrateReceptor beta subunitMuscle cellsTreatment of cellsArterial smooth muscle cellsReceptor substratePretreatment of cellsVascular smooth muscle cellsBeta subunitKinase CPhosphatidylinositolIndependent pathwaysSpecific inhibitorET-1SubunitsPhosphorylationPathway
1997
Activation of the phosphatidylinositol 3-kinase serine kinase by IFN-alpha.
Uddin S, Fish E, Sher D, Gardziola C, White M, Platanias L. Activation of the phosphatidylinositol 3-kinase serine kinase by IFN-alpha. The Journal Of Immunology 1997, 158: 2390-7. PMID: 9036989, DOI: 10.4049/jimmunol.158.5.2390.Peer-Reviewed Original ResearchConceptsSerine kinaseTreatment of cellsIRS-1Kinase assaysSerine kinase activityDual-specificity enzymeP85 regulatory subunitReceptor-generated signalsIRS-1 proteinJak-1 kinasesIFN-alpha-induced activationProtein associatesP85 subunitPhosphoaminoacid analysisRegulatory subunitSerine residuesSerine phosphorylationTyrosine phosphorylationTyk-2STAT-2MAP kinaseKinase activityPretreatment of cellsInhibitor wortmanninPhosphatidylinositol
1996
Tumor Necrosis Factor (TNF)-α Inhibits Insulin Signaling through Stimulation of the p55 TNF Receptor and Activation of Sphingomyelinase*
Peraldi P, Hotamisligil G, Buurman W, White M, Spiegelman B. Tumor Necrosis Factor (TNF)-α Inhibits Insulin Signaling through Stimulation of the p55 TNF Receptor and Activation of Sphingomyelinase*. Journal Of Biological Chemistry 1996, 271: 13018-13022. PMID: 8662983, DOI: 10.1074/jbc.271.22.13018.Peer-Reviewed Original ResearchMeSH Keywords3T3 CellsAdipocytesAnimalsAntigens, CDCell LineCeramidesEnzyme ActivationHumansInsulinInsulin Receptor Substrate ProteinsMicePhosphoproteinsPhosphorylationReceptor, InsulinReceptors, Tumor Necrosis FactorReceptors, Tumor Necrosis Factor, Type ISignal TransductionSphingomyelin PhosphodiesteraseTumor Necrosis Factor-alphaTyrosineConceptsInsulin receptor substrate-1Myeloid 32D cellsInsulin receptorP55 TNF receptorP75 TNF receptorTyrosine phosphorylationInhibits InsulinIRS-2Insulin-dependent tyrosine phosphorylationTNF receptorIRS-1 tyrosine phosphorylationTNF-alphaIR tyrosine kinaseReceptor substrate-1Tyrosine kinase activityNecrosis factorActivation of sphingomyelinaseSerine phosphorylationBiological functionsKinase activitySubstrate-1Tyrosine kinaseExogenous sphingomyelinaseMurine TNF-alphaTumor necrosis factor