2018
Receptor Tyrosine Kinases and the Insulin Signaling System
White M. Receptor Tyrosine Kinases and the Insulin Signaling System. Endocrinology 2018, 121-155. DOI: 10.1007/978-3-319-44675-2_7.Peer-Reviewed Original ResearchProtein tyrosine kinasesTyrosine kinaseExtracellular ligand-binding domainLarge multigene familyRTK family membersInsulin Signaling SystemCell-cell interactionsLigand-binding domainReceptor tyrosine kinasesSystemic nutrient homeostasisPolypeptide growth factorsAspects of metabolismMultigene familyHuman genomeNutrient homeostasisPlasma membraneIntracellular signalsMetabolic regulationSignaling systemInsulin receptorBroader roleHeterologous regulationCell proliferationKinaseGrowth factor
2017
Receptor Tyrosine Kinases and the Insulin Signaling System
White M. Receptor Tyrosine Kinases and the Insulin Signaling System. Endocrinology 2017, 1-34. DOI: 10.1007/978-3-319-27318-1_7-1.Peer-Reviewed Original ResearchProtein tyrosine kinasesTyrosine kinaseExtracellular ligand-binding domainLarge multigene familyRTK family membersInsulin Signaling SystemCell-cell interactionsLigand-binding domainReceptor tyrosine kinasesSystemic nutrient homeostasisPolypeptide growth factorsAspects of metabolismMultigene familyHuman genomeNutrient homeostasisPlasma membraneIntracellular signalsMetabolic regulationSignaling systemInsulin receptorBroader roleHeterologous regulationCell proliferationKinaseGrowth factor
2015
Mapping the path to a longer life
White M. Mapping the path to a longer life. Nature 2015, 524: 170-171. PMID: 26268188, PMCID: PMC4791944, DOI: 10.1038/524170a.Peer-Reviewed Original Research
2013
Nerve Growth Factor Receptor TrkA, a New Receptor in Insulin Signaling Pathway in PC12 Cells*
Geetha T, Rege S, Mathews S, Meakin S, White M, Babu J. Nerve Growth Factor Receptor TrkA, a New Receptor in Insulin Signaling Pathway in PC12 Cells*. Journal Of Biological Chemistry 2013, 288: 23807-23813. PMID: 23749991, PMCID: PMC3745327, DOI: 10.1074/jbc.m112.436279.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid MotifsAmino Acid SequenceAnimalsEnzyme ActivationGlucoseHumansInsulinInsulin Receptor Substrate ProteinsMitogen-Activated Protein Kinase 7Molecular Sequence DataNerve Growth FactorPC12 CellsPhosphorylationPhosphotyrosineProtein BindingProto-Oncogene Proteins c-aktRatsReceptor, InsulinReceptor, trkASignal TransductionConceptsInsulin receptor substrate-1Insulin receptorPC12 cellsTrkA kinase domainTransmembrane receptor tyrosine kinaseKinase-inactive mutantInsulin Signaling PathwayReceptor substrate-1Nerve growth factor receptor TrkAReceptor tyrosine kinasesNerve growth factorActivation of AktNPXY motifKinase domainTyrosine phosphorylationSubstrate-1Regulatory loopTyrosine kinaseSignaling pathwaysGrowth factorNew receptorsReceptor TrkACellsPathwayTrkA
2005
Phosphatase and Tensin Homolog Regulation of Islet Growth and Glucose Homeostasis*
Kushner J, Simpson L, Wartschow L, Guo S, Rankin M, Parsons R, White M. Phosphatase and Tensin Homolog Regulation of Islet Growth and Glucose Homeostasis*. Journal Of Biological Chemistry 2005, 280: 39388-39393. PMID: 16170201, DOI: 10.1074/jbc.m504155200.Peer-Reviewed Original ResearchConceptsInsulin/insulin-like growth factorWild typeIrs2 branchBeta-cell growthInsulin-like growth factorPhosphatase PTENGrowth factorFoxO1 phosphorylationBeta-cell massPTEN expressionAktPTENCascadeSmall isletsGlucose homeostasisInsulin productionGrowthIslet growthSufficient insulinPhosphatidylinositolTolerancePhosphorylationMiceSignalingHomeostasis
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 zetaInsulin Receptor Substrate-2 Deficiency Impairs Brain Growth and Promotes Tau Phosphorylation
Schubert M, Brazil D, Burks D, Kushner J, Ye J, Flint C, Farhang-Fallah J, Dikkes P, Warot X, Rio C, Corfas G, White M. Insulin Receptor Substrate-2 Deficiency Impairs Brain Growth and Promotes Tau Phosphorylation. Journal Of Neuroscience 2003, 23: 7084-7092. PMID: 12904469, PMCID: PMC6740672, DOI: 10.1523/jneurosci.23-18-07084.2003.Peer-Reviewed Original ResearchMeSH KeywordsAge FactorsAnimalsApoptosisBody WeightBrainCell CountCell DivisionCell SurvivalCells, CulturedCerebellumCrosses, GeneticEnzyme InhibitorsHeterozygoteIn Situ Nick-End LabelingInsulin Receptor Substrate ProteinsIntracellular Signaling Peptides and ProteinsMiceMice, KnockoutNeuronsOrgan SizePhosphoproteinsPhosphorylationReceptor, IGF Type 1Signal TransductionTau ProteinsConceptsMolecular linkInsulin receptor substrate (IRS) proteinsBrain growthNeurodegenerative diseasesPancreatic beta-cell functionPeripheral insulin actionSubstrate proteinsBeta-cell functionTyrosine phosphorylationLike growth factorIrs2 branchInsulin resistanceTau phosphorylationIRS2 geneNeuronal proliferationInsulin actionMouse brainInsulin-IGFGrowth factorPhosphorylationIRS2DiabetesBody growthDiseaseMice
2000
Dysregulation of IRS-proteins causes insulin resistance and diabetes
Aguirre V, White M. Dysregulation of IRS-proteins causes insulin resistance and diabetes. Current Opinion In Endocrinology Diabetes And Obesity 2000, 7: 1-7. DOI: 10.1097/00060793-200002000-00001.Peer-Reviewed Original ResearchIRS proteinsInsulin receptor substrate (IRS) proteinsInsulin/insulin-like growth factorPeripheral insulin resistanceType 2 diabetesInsulin resistanceSubstrate proteinsGenetic approachesCommon type 2 diabetesΒ-cell failureInsulin-like growth factorCompensatory insulin secretionDevelopment of diabetesNormal carbohydrate metabolismEarly-onset formCarbohydrate metabolismGrowth factorInsulin secretionDiabetesInsulin actionImportant insightsDysregulationSecretionProteinResistanceDysregulation of IRS-proteins causes insulin resistance and diabetes
Aguirre V, White M. Dysregulation of IRS-proteins causes insulin resistance and diabetes. Current Opinion In Endocrinology Diabetes And Obesity 2000, 7: 1. DOI: 10.1097/00075197-200002000-00001.Peer-Reviewed Original ResearchIRS proteinsPeripheral insulin resistanceInsulin receptor substrate (IRS) proteinsInsulin/insulin-like growth factorType 2 diabetesΒ-cell differentiationInsulin-like growth factorInsulin receptor substrateCompensatory insulin secretionChronic insulin resistanceInsulin resistanceInsulin-signaling pathwayCarbohydrate metabolismInsulin secretionSubstrate proteinsGrowth factorSignal transductionTranscription factorsGenetic approachesCommon type 2 diabetesMolecular basisPancreatic β-cellsReceptor substrateInsulin actionInsulin-signaling system
1998
Insulin-like Growth Factor I (IGF-I)-stimulated Pancreatic β-Cell Growth Is Glucose-dependent SYNERGISTIC ACTIVATION OF INSULIN RECEPTOR SUBSTRATE-MEDIATED SIGNAL TRANSDUCTION PATHWAYS BY GLUCOSE AND IGF-I IN INS-1 CELLS*
Hügl S, White M, Rhodes C. Insulin-like Growth Factor I (IGF-I)-stimulated Pancreatic β-Cell Growth Is Glucose-dependent SYNERGISTIC ACTIVATION OF INSULIN RECEPTOR SUBSTRATE-MEDIATED SIGNAL TRANSDUCTION PATHWAYS BY GLUCOSE AND IGF-I IN INS-1 CELLS*. Journal Of Biological Chemistry 1998, 273: 17771-17779. PMID: 9651378, DOI: 10.1074/jbc.273.28.17771.Peer-Reviewed Original ResearchConceptsInsulin-like growth factor IGrowth factor IBeta-cell proliferationINS-1 cell proliferationCell proliferationFactor IMM glucoseCombination of IGFPancreatic β-cell growthPancreatic beta-cell lineBeta-cell lineΒ-cell growthINS-1 cellsNM IGFBeta-cell mitogenesisCertain growth factorsSignaling mechanismSignal transduction pathwaysGlucose metabolismIGFCell proliferation rateGrowth factorIRS-2Transduction pathwaysGlucose concentrationThe IRS-signalling system: A network of docking proteins that mediate insulin action
White M. The IRS-signalling system: A network of docking proteins that mediate insulin action. Molecular And Cellular Biochemistry 1998, 182: 3-11. PMID: 9609109, DOI: 10.1023/a:1006806722619.Peer-Reviewed Original ResearchConceptsIRS proteinsTyrosine phosphorylationIntrinsic protein tyrosine kinase activityProtein tyrosine kinase activityInsulin-stimulated tyrosine phosphorylationTyrosine kinase activityDocking proteinKinase activityInsulin actionCellular substratesTyrosine kinaseTransmembrane glycoproteinInsulin receptorBiological responsesPhosphorylationGrowth factorComplete understandingNew moleculesTransductionKinaseType II diabetesProteinEnzymeMoleculesII diabetesInsulin 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 cellsThe IRS-signalling system: A network of docking proteins that mediate insulin action
White M. The IRS-signalling system: A network of docking proteins that mediate insulin action. Developments In Molecular And Cellular Biochemistry 1998, 3-11. DOI: 10.1007/978-1-4615-5647-3_1.Peer-Reviewed Original ResearchIRS proteinsTyrosine phosphorylationIntrinsic protein tyrosine kinase activityProtein tyrosine kinase activityInsulin-stimulated tyrosine phosphorylationTyrosine kinase activityDocking proteinKinase activityInsulin actionCellular substratesTyrosine kinaseTransmembrane glycoproteinInsulin receptorBiological responsesPhosphorylationGrowth factorComplete understandingNew moleculesTransductionKinaseType II diabetesProteinEnzymeMoleculesII diabetesThe IRS-Signaling System: A Network of Docking Proteins That Mediate Insulin and Cytokine Action
White M, Yenush L. The IRS-Signaling System: A Network of Docking Proteins That Mediate Insulin and Cytokine Action. Current Topics In Microbiology And Immunology 1998, 228: 179-208. PMID: 9401207, DOI: 10.1007/978-3-642-80481-6_8.Peer-Reviewed Original ResearchConceptsTyrosine phosphorylationSrc homology 2 domainTyrosine autophosphorylation sitesProtein-lipid interactionsAssembly of multicomponentSH2 proteinAutophosphorylation sitesPH domainSpecific membrane receptorsCytosolic substratesReceptor kinaseTyrosine autophosphorylationTransmembrane signalsCellular substratesCytokine receptorsActivity of receptorsMembrane receptorsEarly stepsPhosphorylationProteinKinaseGrowth factorCytokine actionReceptorsCascade
1997
Calmodulin Activates Phosphatidylinositol 3-Kinase*
Joyal J, Burks D, Pons S, Matter W, Vlahos C, White M, Sacks D. Calmodulin Activates Phosphatidylinositol 3-Kinase*. Journal Of Biological Chemistry 1997, 272: 28183-28186. PMID: 9353264, DOI: 10.1074/jbc.272.45.28183.Peer-Reviewed Original ResearchConceptsSrc homology 2 domainIntact cellsPhosphorylation of phosphatidylinositolActivates PhosphatidylinositolVesicular traffickingEukaryotic cellsEffector proteinsRegulatory subunitCytoskeletal organizationUbiquitous Ca2PhosphatidylinositolIntracellular eventsNovel mechanismAffinity chromatographyGrowth factorCalmodulinCalmodulin antagonistsMultiple processesCellsCoimmunoprecipitationDirect linkPhosphorylationTraffickingSubunitsCa2The IRS‐signalling system during insulin and cytokine action
Yenush L, White M. The IRS‐signalling system during insulin and cytokine action. BioEssays 1997, 19: 491-500. PMID: 9204766, DOI: 10.1002/bies.950190608.Peer-Reviewed Original ResearchConceptsIRS-1Grb2-binding proteinGeneral cell growthStructure/function relationshipsAnalysis of miceDrosophila proteinIRS proteinsImportant physiological roleSubstrate recognitionDocking moleculeIntracellular substratesIRS-2Physiological roleCell growthFunction relationshipsProteinDependent diabetes mellitusGrowth factorCytokine actionInsulin actionDiabetes mellitusGlucose metabolismReceptor systemGrowth hormoneIntact animals
1996
Insulin Signal Transduction and the IRS Proteins
Myers M, White M. Insulin Signal Transduction and the IRS Proteins. The Annual Review Of Pharmacology And Toxicology 1996, 36: 615-658. PMID: 8725404, DOI: 10.1146/annurev.pa.36.040196.003151.Peer-Reviewed Original ResearchConceptsIRS proteinsIntracellular tyrosine kinaseBinding of SH2Numerous intracellular signalsTyrosine phosphorylation sitesReceptor-mediated phosphorylationInsulin signal transductionPTB domainCellular physiologyPhosphorylation sitesSignal transductionIntracellular signalsExtracellular domainTyrosine kinaseCytokine receptorsBiochemical eventsInsulin receptorGlucose transportProteinPhosphorylationSignalingGrowth factorSpecific receptorsExciting moleculesPropagation of signals