2013
Insulin receptor substrate‐2 is expressed in kidney epithelium and up‐regulated in diabetic nephropathy
Hookham M, O'Donovan H, Church R, Mercier‐Zuber A, Luzi L, Curran S, Carew R, Droguett A, Mezzano S, Schubert M, White M, Crean J, Brazil D. Insulin receptor substrate‐2 is expressed in kidney epithelium and up‐regulated in diabetic nephropathy. The FEBS Journal 2013, 280: 3232-3243. PMID: 23617393, PMCID: PMC4022317, DOI: 10.1111/febs.12305.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAnimalsBase SequenceBinding SitesBone Morphogenetic Protein 7Case-Control StudiesCell LineChildDiabetic NephropathiesEpitheliumFemaleGene ExpressionHumansInsulin Receptor Substrate ProteinsKidney TubulesMaleMiceMiddle AgedPhosphorylationProtein Processing, Post-TranslationalSignal TransductionSmad4 ProteinTranscriptional ActivationYoung AdultConceptsDiabetic nephropathyBone morphogenetic protein-7DN patientsInsulin receptor substrateChronic kidney disease severityEnd-stage renal diseaseProgression of DNKidney epitheliumTyrosine/serine phosphorylationHuman kidney proximal tubule epithelial cellsKidney disease severityProximal tubule epithelial cellsKidney proximal tubule epithelial cellsHK-2 cellsRole of insulinInsulin receptor substrate 2Growth factor-β1Tubule epithelial cellsIRS2 transcriptionSDS/PAGEIRS proteinsDN progressionRenal diseaseKidney failureMorphogenetic protein-7
2004
Involvement of Insulin Receptor Substrate 2 in Mammary Tumor Metastasis
Nagle J, Ma Z, Byrne M, White M, Shaw L. Involvement of Insulin Receptor Substrate 2 in Mammary Tumor Metastasis. Molecular And Cellular Biology 2004, 24: 9726-9735. PMID: 15509777, PMCID: PMC525494, DOI: 10.1128/mcb.24.22.9726-9735.2004.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisBase SequenceBreast NeoplasmsCell Line, TumorDNA, NeoplasmFemaleHumansInsulin Receptor Substrate ProteinsIntracellular Signaling Peptides and ProteinsMammary Neoplasms, ExperimentalMiceMice, Inbred C57BLMice, KnockoutMice, TransgenicMitosisNeoplasm InvasivenessPhosphoproteinsPhosphorylationConceptsIRS-2Insulin receptor substrate (IRS) proteinsMammary tumor cellsPolyoma virus middle T antigenInsulin receptor substrate 2Middle T antigenGrowth factor deprivationTumor cellsIRS-2 expressionSubstrate proteinsPyV mTMammary tumor metastasisApoptotic stimuliFactor deprivationAdaptor moleculeIncidence of metastasisMitotic cellsMammary fat padMammary tumor progressionBreast cancer metastasisHuman breast cancerSubstrate 2T antigenTumor initiationCancer metastasis
2003
Role of Insulin Receptor Substrates and Protein Kinase C-ζ in Vascular Permeability Factor/Vascular Endothelial Growth Factor Expression in Pancreatic Cancer Cells*
Neid M, Datta K, Stephan S, Khanna I, Pal S, Shaw L, White M, Mukhopadhyay D. Role of Insulin Receptor Substrates and Protein Kinase C-ζ in Vascular Permeability Factor/Vascular Endothelial Growth Factor Expression in Pancreatic Cancer Cells*. Journal Of Biological Chemistry 2003, 279: 3941-3948. PMID: 14604996, DOI: 10.1074/jbc.m303975200.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaBase SequenceCell Line, TumorDNA, NeoplasmFeedbackGene Expression Regulation, NeoplasticHumansInsulin Receptor Substrate ProteinsIntracellular Signaling Peptides and ProteinsNeovascularization, PathologicPancreatic NeoplasmsPhosphoproteinsProtein Kinase CSignal TransductionSp1 Transcription FactorVascular Endothelial Growth Factor AConceptsVPF/VEGF expressionIRS proteinsIRS-2Negative feedback loopVEGF transcriptionPKC-zetaVascular Permeability Factor/Vascular Endothelial Growth Factor ExpressionPancreatic cancer cellsProtein kinase C zetaCancer cellsInsulin receptor substrate-1IGF-1RReceptor substrate-1Insulin receptor substrateIRS-2 proteinProtein kinase CMajor downstream moleculesInsulin-like growth factor receptorRenal cancer cellsVascular permeability factor/vascular endothelial growth factorIGF-1R signalingGrowth factorRas pathwayGrowth factor receptorC zeta
1999
Search for variants of the gene-promoter and the potential phosphotyrosine encoding sequence of the insulin receptor substrate-2 gene: evaluation of their relation with alterations in insulin secretion and insulin sensitivity
Almind K, Frederiksen S, Bernal D, Hansen T, Ambye L, Urhammer S, Ekstrøm C, Berglund L, Reneland R, Lithell H, White M, Van Obberghen E, Pedersen O. Search for variants of the gene-promoter and the potential phosphotyrosine encoding sequence of the insulin receptor substrate-2 gene: evaluation of their relation with alterations in insulin secretion and insulin sensitivity. Diabetologia 1999, 42: 1244-1249. PMID: 10525667, DOI: 10.1007/s001250051299.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAgedAmino Acid SubstitutionBase SequenceDiabetes Mellitus, Type 2Gene FrequencyGenetic Carrier ScreeningGenetic TestingGlucose Tolerance TestHumansInsulinInsulin Receptor Substrate ProteinsInsulin SecretionIntracellular Signaling Peptides and ProteinsMaleMiddle AgedMolecular Sequence DataPedigreePhosphoproteinsPhosphotyrosinePolymorphism, Single-Stranded ConformationalPromoter Regions, GeneticProspective StudiesTwo-Hybrid System TechniquesConceptsType II diabetic patientsII diabetic patientsSerum insulin concentrationsInsulin secretionDiabetic patientsInsulin sensitivityInsulin concentrationsGly1057Asp variantInsulin receptor substrate-2 (IRS-2) geneIntravenous glucose tolerance testGlucose-tolerant offspringGlucose tolerance testGlucose-tolerant subjectsIRS-2Elderly Swedish menMiddle-aged subjectsYoung healthy subjectsAmino acid variantsWildtype carriersDiabetic parentsTolerance testTolerant subjectsHealthy subjectsStudy groupInsulin sensivity
1998
Mapping of the human insulin receptor substrate-2 gene, identification of a linked polymorphic marker and linkage analysis in families with Type II diabetes: no evidence for a major susceptibility role
Kalidas K, Wasson J, Glaser B, Meyer J, Duprat L, White M, Permutt M. Mapping of the human insulin receptor substrate-2 gene, identification of a linked polymorphic marker and linkage analysis in families with Type II diabetes: no evidence for a major susceptibility role. Diabetologia 1998, 41: 1389-1391. PMID: 9833949, DOI: 10.1007/s001250051081.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBase SequenceChromosome MappingChromosomes, Human, Pair 13Diabetes Mellitus, Type 1Europe, EasternGenetic Carrier ScreeningGenetic LinkageGenetic MarkersGenotypeHumansInsulin Receptor Substrate ProteinsIntracellular Signaling Peptides and ProteinsJewsMiceMicrosatellite RepeatsPhosphoproteinsPolymorphism, GeneticStatistics, NonparametricConceptsIRS-2 geneRadiation hybrid panel mappingPolymorphic markersInsulin receptor substrate 2Nonparametric linkage analysisMap positionChromosome 13q34Evidence of linkageInsulin receptor substrate-2 (IRS-2) geneGene regionLinkage analysisGenesSubstrate 2Excess alleleInsulin receptorNearby markersType II diabetesAshkenazi Jewish familiesMice resultsII diabetesSusceptibility roleMarkersFamilyPeripheral insulin resistanceA 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 contributes
1997
The IRS-2 gene on murine chromosome 8 encodes a unique signaling adapter for insulin and cytokine action.
Sun X, Pons S, Wang L, Zhang Y, Yenush L, Burks D, Myers M, Glasheen E, Copeland N, Jenkins N, Pierce J, White M. The IRS-2 gene on murine chromosome 8 encodes a unique signaling adapter for insulin and cytokine action. Endocrinology 1997, 11: 251-62. PMID: 9013772, DOI: 10.1210/mend.11.2.9885.Peer-Reviewed Original ResearchMeSH Keywords3T3 CellsAmino Acid SequenceAnimalsBase SequenceCell DifferentiationCells, CulturedChromosome MappingChromosomesCytokinesInsulinInsulin Receptor Substrate ProteinsInterleukin-4Intracellular Signaling Peptides and ProteinsMiceMolecular Sequence DataPhosphoproteinsPhosphorylationSequence Homology, Amino AcidSignal TransductionTissue DistributionTyrosineConceptsMurine chromosome 8IRS-2IRS-1IRS-2 geneIRS proteinsExpression patternsSrc homology 2 domainChromosome 8Recombinant SH2 domainsSpecific expression patternsMurine chromosome 1Amino acid sequenceDifferential tyrosine phosphorylationMurine hematopoietic cellsDistinct phosphorylation patternsSH2 domainSignal transductionSingle exonPhosphorylation patternTyrosine phosphorylationIL-4 stimulationAcid sequenceChromosome 1Signaling adapterCytokine signaling
1996
The Fyn Tyrosine Kinase Binds Irs-1 and Forms a Distinct Signaling Complex during Insulin Stimulation (∗)
Sun X, Pons S, Asano T, Myers M, Glasheen E, White M. The Fyn Tyrosine Kinase Binds Irs-1 and Forms a Distinct Signaling Complex during Insulin Stimulation (∗). Journal Of Biological Chemistry 1996, 271: 10583-10587. PMID: 8631859, DOI: 10.1074/jbc.271.18.10583.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsBase SequenceCHO CellsCricetinaeDNA PrimersEnzyme ActivationInsulinInsulin Receptor Substrate ProteinsMiceMolecular Sequence DataPhosphoproteinsProtein-Tyrosine KinasesProto-Oncogene ProteinsProto-Oncogene Proteins c-fynSignal TransductionSrc Homology DomainsSubstrate SpecificityConceptsSrc homology 2Grb-2Insulin stimulationTyrosine phosphorylation sitesInsulin/IGFSH2 domainSH2 proteinSignaling ComplexHomology 2Related Src kinasesPhosphorylation sitesIR-1Src kinaseExpression libraryP59fyn kinaseTyrosine residuesP59fynInsulin receptorIR proteinProteinSpecific associationComplexesKinaseReceptorsP85Insulin Receptor Substrate-2 Binds to the Insulin Receptor through Its Phosphotyrosine-binding Domain and through a Newly Identified Domain Comprising Amino Acids 591–786 (∗)
Sawka-Verhelle D, Tartare-Deckert S, White M, Van Obberghen E. Insulin Receptor Substrate-2 Binds to the Insulin Receptor through Its Phosphotyrosine-binding Domain and through a Newly Identified Domain Comprising Amino Acids 591–786 (∗). Journal Of Biological Chemistry 1996, 271: 5980-5983. PMID: 8626379, DOI: 10.1074/jbc.271.11.5980.Peer-Reviewed Original ResearchConceptsTwo-hybrid systemIRS-2IRS-1Insulin receptorNPEY motifNPXY motifPhosphotyrosine-binding (PTB) domainPleckstrin homology domainTyrosine phosphorylation sitesActivated insulin receptorInsulin receptor kinaseIRS-2 phosphorylationReceptor tyrosine kinase activityTyrosine kinase activityAmino acids 591IRS proteinsHomology domainPhosphorylation sitesInteraction domainReceptor kinaseCytoplasmic portionBinding domainsKinase activityRegulatory loopNH2 terminus