2001
Dynamic regulation of metabolism and respiration by endogenously produced nitric oxide protects against oxidative stress
Paxinou E, Weisse M, Chen Q, Souza J, Hertkorn C, Selak M, Daikhin E, Yudkoff M, Sowa G, Sessa W, Ischiropoulos H. Dynamic regulation of metabolism and respiration by endogenously produced nitric oxide protects against oxidative stress. Proceedings Of The National Academy Of Sciences Of The United States Of America 2001, 98: 11575-11580. PMID: 11562476, PMCID: PMC58771, DOI: 10.1073/pnas.201293198.Peer-Reviewed Original ResearchConceptsEndothelial nitric oxide synthaseNitric oxideOxidative stressProtective effectNitric oxide protectsNitric oxide synthaseNitric oxide synthesisECV304 cellsSteady-state levelsMechanism of protectionOxide synthaseOxide synthesisENOS cDNAHuman ECV304 cellsMitochondria respirationDeathMitochondrial respirationExposureSame extentCellsCell metabolismDynamic regulationMetabolismLow steady-state levelsGlycolytic pathwayAkt-Mediated Phosphorylation of the G Protein-Coupled Receptor EDG-1 Is Required for Endothelial Cell Chemotaxis
Lee M, Thangada S, Paik J, Sapkota G, Ancellin N, Chae S, Wu M, Morales-Ruiz M, Sessa W, Alessi D, Hla T. Akt-Mediated Phosphorylation of the G Protein-Coupled Receptor EDG-1 Is Required for Endothelial Cell Chemotaxis. Molecular Cell 2001, 8: 693-704. PMID: 11583630, DOI: 10.1016/s1097-2765(01)00324-0.Peer-Reviewed Original ResearchMeSH KeywordsActinsAnimalsCell LineChemotaxisEndothelium, VascularEnzyme ActivationHumansImmediate-Early ProteinsLysophospholipidsModels, BiologicalNeovascularization, PhysiologicPhosphorylationProtein BindingProtein Serine-Threonine KinasesProtein Structure, TertiaryProto-Oncogene ProteinsProto-Oncogene Proteins c-aktRac GTP-Binding ProteinsReceptors, Cell SurfaceReceptors, G-Protein-CoupledReceptors, LysophospholipidRecombinant Fusion ProteinsSignal TransductionSphingosineConceptsG protein-coupled receptor Edg-1EDG-1Cell migrationRac activationAkt-Mediated PhosphorylationCortical actin assemblyProtein kinase AktThird intracellular loopAkt bindsActin assemblyEndothelial cell migrationKinase AktSpecificity switchEndothelial cell chemotaxisCellular phenomenaDependent signalingIntracellular loopAktCell chemotaxisTransactivationPhosphorylationGPCRsChemotaxisActivationMutantsAkt Down-regulation of p38 Signaling Provides a Novel Mechanism of Vascular Endothelial Growth Factor-mediated Cytoprotection in Endothelial Cells*
Gratton J, Morales-Ruiz M, Kureishi Y, Fulton D, Walsh K, Sessa W. Akt Down-regulation of p38 Signaling Provides a Novel Mechanism of Vascular Endothelial Growth Factor-mediated Cytoprotection in Endothelial Cells*. Journal Of Biological Chemistry 2001, 276: 30359-30365. PMID: 11387313, DOI: 10.1074/jbc.m009698200.Peer-Reviewed Original ResearchMeSH KeywordsAdenoviridaeAnimalsApoptosisBlotting, WesternCattleCell DeathCell LineCell SurvivalCells, CulturedDose-Response Relationship, DrugDown-RegulationEndothelial Growth FactorsEndothelium, VascularEnzyme ActivationEnzyme InhibitorsFlow CytometryHumansImidazolesLymphokinesMitogen-Activated Protein KinasesP38 Mitogen-Activated Protein KinasesPhosphatidylinositol 3-KinasesPhosphorylationProtein BindingProtein Serine-Threonine KinasesProto-Oncogene ProteinsProto-Oncogene Proteins c-aktPyridinesSignal TransductionTime FactorsUmbilical VeinsVascular Endothelial Growth Factor AVascular Endothelial Growth FactorsConceptsMEKK3 phosphorylationP38 activationMEKK3 kinase activityMitogen-activated protein kinaseP38 mitogen-activated protein kinaseP38-dependent apoptosisP38 MAPK inhibitor SB203580Dominant-negative RacInhibition of PIActivation of MKK3/6Vascular endothelial growth factorMAPK inhibitor SB203580P38 MAPK pathwayP38 MAPK activationEndothelial cellsEndothelial cell survivalGrowth factorRac activationProtein kinaseActive AktPro-apoptotic effectsKinase activityInhibitor SB203580MAPK activationP38 signaling
2000
Direct Interaction between Endothelial Nitric-oxide Synthase and Dynamin-2 IMPLICATIONS FOR NITRIC-OXIDE SYNTHASE FUNCTION*
Cao S, Yao J, McCabe T, Yao Q, Katusic Z, Sessa W, Shah V. Direct Interaction between Endothelial Nitric-oxide Synthase and Dynamin-2 IMPLICATIONS FOR NITRIC-OXIDE SYNTHASE FUNCTION*. Journal Of Biological Chemistry 2000, 276: 14249-14256. PMID: 11120737, DOI: 10.1074/jbc.m006258200.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAortaBlotting, WesternCalcimycinCattleCell LineDose-Response Relationship, DrugDynamin IDynaminsEndothelium, VascularGlutathione TransferaseGolgi ApparatusGTP PhosphohydrolasesIonophoresKineticsMicroscopy, ConfocalMicroscopy, FluorescenceNitric Oxide SynthaseNitric Oxide Synthase Type IIIPrecipitin TestsProtein BindingProtein BiosynthesisRatsRecombinant Fusion ProteinsTransfectionConceptsDynamin 2Bovine aortic endothelial cellsRecombinant eNOS proteinDirect protein-protein interactionDouble-label confocal immunofluorescenceProtein-protein interactionsSpecific protein interactionsDirect interactionClone 9 cellsEndothelial nitric oxide synthaseMembrane compartmentsLarge GTPaseGlutathione S-transferaseProtein interactionsNovel functionDynaminECV-304 cellsSynthase functionIntracellular signalsMembrane distributionConfocal immunofluorescenceFluorescent proteinENOS regulationGreen fluorescentProtein
1998
Dynamic activation of endothelial nitric oxide synthase by Hsp90
García-Cardeña G, Fan R, Shah V, Sorrentino R, Cirino G, Papapetropoulos A, Sessa W. Dynamic activation of endothelial nitric oxide synthase by Hsp90. Nature 1998, 392: 821-824. PMID: 9580552, DOI: 10.1038/33934.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibiotics, AntineoplasticAortaBenzoquinonesCattleCell LineCOS CellsEndothelial Growth FactorsEndothelium, VascularEnzyme ActivationHistamineHSP90 Heat-Shock ProteinsHumansLactams, MacrocyclicLymphokinesMuscle RelaxationNitric OxideNitric Oxide SynthasePrecipitin TestsQuinonesRatsSignal TransductionStress, MechanicalTransfectionVascular Endothelial Growth Factor AVascular Endothelial Growth FactorsConceptsActivation of eNOSCellular targetsHeat shock protein 90Binding of HSP90Specific cellular targetsEndothelial nitric oxide synthaseMolecular chaperonesHsp90 associatesSignaling proteinsProtein foldingProtein 90Mechanotransduction pathwaysENOS complexG proteinsFluid shear stressHsp90Activation statePrecise roleGrowth factorDynamic activationVascular endothelial growth factorSynthaseNitric oxide synthaseEndothelial growth factorActivation
1997
Substrate Binding and Calmodulin Binding to Endothelial Nitric Oxide Synthase Coregulate Its Enzymatic Activity
Presta A, Liu J, Sessa W, Stuehr D. Substrate Binding and Calmodulin Binding to Endothelial Nitric Oxide Synthase Coregulate Its Enzymatic Activity. Nitric Oxide 1997, 1: 74-87. PMID: 9701047, DOI: 10.1006/niox.1996.0110.Peer-Reviewed Original Research
1996
Palmitoylation of Endothelial Nitric Oxide Synthase Is Necessary for Optimal Stimulated Release of Nitric Oxide: Implications for Caveolae Localization †
Liu J, García-Cardeña G, Sessa W. Palmitoylation of Endothelial Nitric Oxide Synthase Is Necessary for Optimal Stimulated Release of Nitric Oxide: Implications for Caveolae Localization †. Biochemistry 1996, 35: 13277-13281. PMID: 8873592, DOI: 10.1021/bi961720e.Peer-Reviewed Original ResearchConceptsPalmitoylation-deficient mutantMembrane associationN-myristoylationWT enzymeLocalization of eNOSActivation of eNOSEndothelial nitric oxide synthaseCaveolae membranesCaveolar localizationPalmitoylationCysteine palmitoylationWT proteinGolgi complexMutantsIntact cellsCaveolaeVivo significanceHigh saltEnzymeCellsSynthaseNitric oxide synthaseTriton XLocalizationImportant role