2003
cAMP promotes pancreatic β-cell survival via CREB-mediated induction of IRS2
Jhala U, Canettieri G, Screaton R, Kulkarni R, Krajewski S, Reed J, Walker J, Lin X, White M, Montminy M. cAMP promotes pancreatic β-cell survival via CREB-mediated induction of IRS2. Genes & Development 2003, 17: 1575-1580. PMID: 12842910, PMCID: PMC196130, DOI: 10.1101/gad.1097103.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisCell LineCell SurvivalColforsinCyclic AMPCyclic AMP Response Element-Binding ProteinDiabetes MellitusGene Expression RegulationGlucagonGlucagon-Like Peptide 1GlucoseGlucose IntoleranceHumansInsulinInsulin Receptor Substrate ProteinsInsulin-Like Growth Factor IIntracellular Signaling Peptides and ProteinsIslets of LangerhansMiceMice, TransgenicPeptide FragmentsPhosphoproteinsPhosphorylationPromoter Regions, GeneticProtein PrecursorsProtein Serine-Threonine KinasesProto-Oncogene ProteinsProto-Oncogene Proteins c-aktSignal TransductionTransfectionTransgenesTumor Cells, CulturedConceptsPancreatic β-cell survivalActivity of CREBSecond messenger cAMPSurvival kinase AktΒ-cell survivalKinase AktPathway componentsA-CREBCREB actionExpression of IRS2Cell survivalBeta-cell apoptosisDirect targetIslet cell survivalNovel mechanismCREBIRS2ExpressionCAMPInductionTransgeneAktIGF-1ApoptosisSurvival
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-1
1998
Differential Regulation of Insulin Receptor Substrate-2 and Mitogen-Activated Protein Kinase Tyrosine Phosphorylation by Phosphatidylinositol 3-Kinase Inhibitors in SH-SY5Y Human Neuroblastoma Cells*This work was supported by NIH Grants R29-NS-32843 and R01-NS-36778, grants from the American Diabetes Association and Juvenile Diabetes Foundation (to E.L.F.), and a grant from the Millie Schembechler Adrenal Research Fund of the University of Michigan Comprehensive Cancer Center (to E.L.F. and P.S.L.).
Kim B, Leventhal P, White M, Feldman E. Differential Regulation of Insulin Receptor Substrate-2 and Mitogen-Activated Protein Kinase Tyrosine Phosphorylation by Phosphatidylinositol 3-Kinase Inhibitors in SH-SY5Y Human Neuroblastoma Cells*This work was supported by NIH Grants R29-NS-32843 and R01-NS-36778, grants from the American Diabetes Association and Juvenile Diabetes Foundation (to E.L.F.), and a grant from the Millie Schembechler Adrenal Research Fund of the University of Michigan Comprehensive Cancer Center (to E.L.F. and P.S.L.). Endocrinology 1998, 139: 4881-4889. PMID: 9832424, DOI: 10.1210/endo.139.12.6348.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAdaptor Proteins, Vesicular TransportCalcium-Calmodulin-Dependent Protein KinasesElectrophoresis, Polyacrylamide GelEnzyme InhibitorsGRB2 Adaptor ProteinHumansInsulin Receptor Substrate ProteinsInsulin-Like Growth Factor IIntracellular Signaling Peptides and ProteinsIsoenzymesMitogen-Activated Protein Kinase 1NeuritesNeuroblastomaPhosphatidylinositol 3-KinasesPhosphoinositide-3 Kinase InhibitorsPhosphoproteinsPhosphorylationProteinsShc Signaling Adaptor ProteinsSrc Homology 2 Domain-Containing, Transforming Protein 1Tumor Cells, CulturedTyrosineConceptsInsulin receptor substrate 2IRS-2 tyrosine phosphorylationMitogen-activated protein kinase activationTyrosine phosphorylationProtein kinase activationKinase activationSerine/threonine phosphorylationSubstrate 2Association of Grb2Neurite outgrowthSH-SY5Y human neuroblastomaThreonine phosphorylationNegative regulationSH-SY5Y human neuroblastoma cellsIRS-1Grb2Nervous system growthDifferential regulationPhosphorylationHuman neuroblastoma cellsNeuronal cellsPhosphatidylinositolPI 3Concentration-dependent mannerInsulin-like growth factor IA specific increased expression of insulin receptor substrate 2 in pancreatic beta-cell lines is involved in mediating serum-stimulated beta-cell growth.
Schuppin G, Pons S, Hügl S, Aiello L, King G, White M, Rhodes C. A specific increased expression of insulin receptor substrate 2 in pancreatic beta-cell lines is involved in mediating serum-stimulated beta-cell growth. Diabetes 1998, 47: 1074-1085. PMID: 9648831, DOI: 10.2337/diabetes.47.7.1074.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBase SequenceBloodCell DifferentiationCell DivisionDNAGene ExpressionGenes, fosGenes, junInsulin Receptor Substrate ProteinsInsulinomaIntracellular Signaling Peptides and ProteinsIslets of LangerhansMitogensMolecular Sequence DataPancreatic NeoplasmsPhosphoproteinsRatsRetroelementsRNA, MessengerSignal TransductionTumor Cells, CulturedConceptsSignal transduction pathwaysIRS-2 expressionPancreatic beta-cell lineIRS-2Protein kinaseTransduction pathwaysBeta-cell lineGene expressionIRS-2 gene expressionSevenless-1 proteinBeta-cell growthDifferential mRNA display analysisMitogen-activated protein kinaseDifferential gene expressionTyrosine protein kinaseInsulin receptor substrate 2Insulinoma cellsInsulin receptor substrateGene candidate approachSerum-stimulated DNA synthesisPancreatic beta-cell growthRibosomal proteinsProtein complexesMRNA levelsBeta-cells contributesInsulin Receptor Substrate-1 is the Predominant Signaling Molecule Activated by Insulin-like Growth Factor-I, Insulin, and Interleukin-4 in Estrogen Receptor-positive Human Breast Cancer Cells*
Jackson J, White M, Yee D. Insulin Receptor Substrate-1 is the Predominant Signaling Molecule Activated by Insulin-like Growth Factor-I, Insulin, and Interleukin-4 in Estrogen Receptor-positive Human Breast Cancer Cells*. Journal Of Biological Chemistry 1998, 273: 9994-10003. PMID: 9545345, DOI: 10.1074/jbc.273.16.9994.Peer-Reviewed Original ResearchMeSH KeywordsAndrostadienesBreast NeoplasmsCalcium-Calmodulin-Dependent Protein KinasesEnzyme InhibitorsFemaleFlavonoidsHumansInsulinInsulin Receptor Substrate ProteinsInsulin-Like Growth Factor IInterleukin-4Intracellular Signaling Peptides and ProteinsKineticsMitogen-Activated Protein Kinase KinasesPhosphatidylinositol 3-KinasesPhosphoinositide-3 Kinase InhibitorsPhosphoproteinsPhosphorylationPhosphotyrosineProtein Kinase InhibitorsProtein KinasesReceptor, InsulinReceptors, EstrogenSignal TransductionTumor Cells, CulturedWortmanninConceptsIRS-1Tyrosine phosphorylationIRS-2Insulin-like growth factorBreast cancer cellsIGF-I treatmentGreater tyrosine phosphorylationInterleukin-4Substrate adaptor proteinMitogen-activated protein kinase activityCancer cellsCell linesInsulin receptor substrate-1Mitogen-activated protein kinaseP85 regulatory subunitProtein kinase activityActivation of phosphatidylinositolReceptor substrate-1Estrogen receptor-positive human breast cancer cellsGrowth factorPrimary breast tumor specimensIGF-stimulated growthAdaptor proteinRegulatory subunitT47-D breast cancer cells
1997
The IRS-pathway operates distinctively from the Stat-pathway in hematopoietic cells and transduces common and distinct signals during engagement of the insulin or interferon-alpha receptors.
Uddin S, Fish E, Sher D, Gardziola C, Colamonici O, Kellum M, Pitha P, White M, Platanias L. The IRS-pathway operates distinctively from the Stat-pathway in hematopoietic cells and transduces common and distinct signals during engagement of the insulin or interferon-alpha receptors. Blood 1997, 90: 2574-82. PMID: 9326223.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBurkitt LymphomaDNA-Binding ProteinsHematopoietic Stem CellsHumansInsulinInsulin Receptor Substrate ProteinsInsulin-Like Growth Factor IInterferon-alphaIntracellular Signaling Peptides and ProteinsLeukemia, Myelomonocytic, AcuteLeukemia-Lymphoma, Adult T-CellMiceMultiple MyelomaNeoplasm ProteinsPhosphoproteinsReceptor, InsulinReceptor, Interferon alpha-betaReceptors, InterferonSignal TransductionSrc Homology DomainsSTAT1 Transcription FactorSTAT2 Transcription FactorSTAT3 Transcription FactorTrans-ActivatorsTumor Cells, CulturedConceptsSTAT pathwaySH2 domainHematopoietic cellsInsulin/insulin-like growth factorIRS pathwayDistinct downstream signalsTHP-1 cellsIRS-1 functionInsulin/IGFActivator of transcriptionInsulin receptor substrateDistinct signalsIFN-alphaHuman myelomonocytic cellsDocking proteinMouse myeloid cellsGrb-2P85 subunitInterferon alpha receptorSTAT-2Receptor substrateVesicular stomatitis virusSignal transducerIRS-2IRS-1Interaction of p59fynwith Interferon-Activated Jak Kinases
Uddin S, Sher D, Alsayed Y, Pons S, Colamonici O, Fish E, White M, Platanias L. Interaction of p59fynwith Interferon-Activated Jak Kinases. Biochemical And Biophysical Research Communications 1997, 235: 83-88. PMID: 9196040, DOI: 10.1006/bbrc.1997.6741.Peer-Reviewed Original ResearchAntibodies, MonoclonalBlotting, WesternGlutathione TransferaseHumansInterferon Type IInterferon-gammaJanus Kinase 1Janus Kinase 2PhosphotyrosineProteinsProtein-Tyrosine KinasesProto-Oncogene MasProto-Oncogene ProteinsProto-Oncogene Proteins c-cblProto-Oncogene Proteins c-fynRecombinant Fusion ProteinsRecombinant ProteinsSignal TransductionSrc Homology DomainsTumor Cells, CulturedTYK2 KinaseUbiquitin-Protein LigasesActivation 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