2009
Breathing Room: The (Un)Natural History of Adipose Microhypoxia and Insulin Resistance
Copps K, White M. Breathing Room: The (Un)Natural History of Adipose Microhypoxia and Insulin Resistance. Diabetes 2009, 58: 26-27. PMID: 19114728, PMCID: PMC2606882, DOI: 10.2337/db08-1517.Peer-Reviewed Original Research
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
Essential role of protein kinase Cζ in the impairment of insulin‐induced glucose transport in IRS‐2‐deficient brown adipocytes
Arribas M, Valverde A, Burks D, Klein J, Farese R, White M, Benito M. Essential role of protein kinase Cζ in the impairment of insulin‐induced glucose transport in IRS‐2‐deficient brown adipocytes. FEBS Letters 2003, 536: 161-166. PMID: 12586357, DOI: 10.1016/s0014-5793(03)00049-8.Peer-Reviewed Original ResearchConceptsGLUT4 translocationIRS-2/PIBrown adipocytesInsulin-induced glucose transportProtein kinase C zetaIRS-2-associated phosphatidylinositolKinase-inactive mutantGlucose uptakeWild-type cellsProtein kinase CζEssential roleInsulin receptor substrate-2-deficient (IRS2(-/-)) miceC zetaPKC-zetaMolecular mechanismsIRS-2Impaired glucose uptakeGlucose transportAdipocytesTranslocationCellsUptakeMutantsPhosphatidylinositolCζ
2001
Regulation 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 cycle
2000
Essential Role of Insulin Receptor Substrate-2 in Insulin Stimulation of Glut4 Translocation and Glucose Uptake in Brown Adipocytes*
Fasshauer M, Klein J, Ueki K, Kriauciunas K, Benito M, White M, Kahn C. Essential Role of Insulin Receptor Substrate-2 in Insulin Stimulation of Glut4 Translocation and Glucose Uptake in Brown Adipocytes*. Journal Of Biological Chemistry 2000, 275: 25494-25501. PMID: 10829031, DOI: 10.1074/jbc.m004046200.Peer-Reviewed Original ResearchMeSH KeywordsAdipocytesAdipose Tissue, BrownAnimalsArabidopsis ProteinsAzo CompoundsBiological TransportCell DifferentiationCell MembraneCells, CulturedColoring AgentsDose-Response Relationship, DrugGlucoseGlucose Transporter Type 4ImmunoblottingInsulinInsulin Receptor Substrate ProteinsIntracellular Signaling Peptides and ProteinsMiceMice, KnockoutMonosaccharide Transport ProteinsMuscle ProteinsPhosphatidylinositol 3-KinasesPhosphoproteinsPhosphorylationPlant ProteinsPlasmidsPotassium ChannelsPrecipitin TestsProtein Serine-Threonine KinasesProto-Oncogene ProteinsProto-Oncogene Proteins c-aktRetroviridaeSignal TransductionSubcellular FractionsTime FactorsConceptsInsulin-stimulated GLUT4 translocationGLUT4 translocationInsulin-induced glucose uptakeIRS-2Plasma membraneDownstream effectorsWild typeInsulin receptor substrate (IRS) proteinsBrown adipocyte cell lineInsulin stimulationGlycogen synthase kinase-3IRS-2-associated phosphatidylinositolGlucose uptakeAkt-dependent phosphorylationInsulin receptor substrate 2Synthase kinase-3Brown adipocytesMajor downstream effectorActivity of AktMature brown adipocytesAdipocyte cell lineSubstrate proteinsWild-type counterpartsKO cellsKinase 3
1998
Insulin receptor substrate (IRS) proteins IRS-1 and IRS-2 differential signaling in the insulin/insulin-like growth factor-I pathways in fetal brown adipocytes.
Valverde A, Lorenzo M, Pons S, White M, Benito M. Insulin receptor substrate (IRS) proteins IRS-1 and IRS-2 differential signaling in the insulin/insulin-like growth factor-I pathways in fetal brown adipocytes. Endocrinology 1998, 12: 688-97. PMID: 9605931, DOI: 10.1210/mend.12.5.0106.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAdipocytesAdipose Tissue, BrownAmino Acid SequenceAnimalsEnzyme ActivationFetusGRB2 Adaptor ProteinInsulinInsulin Receptor Substrate ProteinsInsulin-Like Growth Factor IIntracellular Signaling Peptides and ProteinsMolecular Sequence DataPhosphatidylinositol 3-KinasesPhosphoproteinsPhosphorylationProtein BindingProteinsRatsRats, WistarReceptor, InsulinSignal TransductionSrc Homology DomainsTyrosineConceptsInsulin/IGFInsulin receptor substrateIRS-1IRS-2Shc proteinsTyrosine phosphorylationInsulin receptor substrate (IRS) proteinsInsulin/insulin-like growth factorFetal rat brown adipocytesIRS-2-associated phosphatidylinositolIRS-2 tyrosine phosphorylationFetal brown adipocytesProtein kinase signal pathwayBrown adipocytesKinase signal pathwayBrown adipocyte proliferationInsulin/insulinSubstrate proteinsSH2 domainGrb-2Thermogenic differentiationFetal brown adipose tissueReceptor substrateFusion proteinInsulin-like growth factor
1997
The 60 kDa Insulin Receptor Substrate Functions Like an IRS Protein (pp60IRS3) in Adipose Cells †
Smith-Hall J, Pons S, Patti M, Burks D, Yenush L, Sun X, Kahn C, White M. The 60 kDa Insulin Receptor Substrate Functions Like an IRS Protein (pp60IRS3) in Adipose Cells †. Biochemistry 1997, 36: 8304-8310. PMID: 9204876, DOI: 10.1021/bi9630974.Peer-Reviewed Original ResearchMeSH KeywordsAdipocytesAnimalsImmunosorbent TechniquesInsulinInsulin Receptor Substrate ProteinsIntracellular Signaling Peptides and ProteinsMaleMiceMolecular WeightPhosphatidylinositol 3-KinasesPhosphoproteinsPhosphotransferases (Alcohol Group Acceptor)PhosphotyrosineRatsRats, Sprague-DawleyReceptor, InsulinTestisConceptsIRS-1IRS proteinsInsulin receptor substrates functionIRS-2IRS protein familyTyrosine phosphorylated proteinsInsulin receptor signalsInsulin receptor substratePTB domainNPXY motifSH2 domainProtein familyPhosphorylated proteinsReceptor substrateInsulin stimulationReceptor signalsSubstrate functionP85New memberProteinRat adipocytesAdipose cellsAlternate pathwayFunctional characteristicsSynthetic peptides
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