2001
Akt-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 signalingSphingosine 1-Phosphate Activates Akt, Nitric Oxide Production, and Chemotaxis through a GiProtein/Phosphoinositide 3-Kinase Pathway in Endothelial Cells*
Morales-Ruiz M, Lee M, Zöllner S, Gratton J, Scotland R, Shiojima I, Walsh K, Hla T, Sessa W. Sphingosine 1-Phosphate Activates Akt, Nitric Oxide Production, and Chemotaxis through a GiProtein/Phosphoinositide 3-Kinase Pathway in Endothelial Cells*. Journal Of Biological Chemistry 2001, 276: 19672-19677. PMID: 11278592, DOI: 10.1074/jbc.m009993200.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBlotting, NorthernBlotting, WesternCattleCell MovementChemotaxisCulture Media, Serum-FreeDose-Response Relationship, DrugEndothelial Growth FactorsEndothelium, VascularEnzyme ActivationGenes, DominantGTP-Binding Protein alpha Subunits, Gi-GoLungLymphokinesLysophospholipidsNeovascularization, PhysiologicNitric OxideNitric Oxide SynthaseNitric Oxide Synthase Type IIIPhosphatidylinositol 3-KinasesPhosphorylationProtein BindingProtein Serine-Threonine KinasesProto-Oncogene ProteinsProto-Oncogene Proteins c-aktReceptors, Cell SurfaceSignal TransductionSphingosineTime FactorsVascular Endothelial Growth Factor AVascular Endothelial Growth FactorsVirulence Factors, BordetellaConceptsEndothelial differentiation gene familySerine/threonine kinase AktHeterotrimeric G proteinsThreonine kinase AktEDG-1 receptorGene familyAkt substrateKinase AktEndothelial cell chemotaxisActivates AktENOS phosphorylationAkt activationG proteinsCell survivalEndothelial nitric oxide synthasePhosphorylationAktCell chemotaxisSppSignalingGrowth factorVascular endothelial growth factorChemotaxisEndothelial cellsSphingosine
2000
The HMG-CoA reductase inhibitor simvastatin activates the protein kinase Akt and promotes angiogenesis in normocholesterolemic animals.
Kureishi Y, Luo Z, Shiojima I, Bialik A, Fulton D, Lefer D, Sessa W, Walsh K. The HMG-CoA reductase inhibitor simvastatin activates the protein kinase Akt and promotes angiogenesis in normocholesterolemic animals. Nature Medicine 2000, 6: 1004-1010. PMID: 10973320, PMCID: PMC2828689, DOI: 10.1038/79510.Peer-Reviewed Original ResearchConceptsProtein kinase Akt/PKBKinase Akt/PKBProtein kinase AktAkt/PKBAkt-dependent mannerVascular structure formationActivation of AktKinase AktVascular endothelial growth factor treatmentEnhanced phosphorylationBlood vessel growthNew blood vessel growthAktGrowth factor treatmentVessel growthEndothelial cellsEndothelial nitric oxide synthaseRecent studiesHMG-CoA reductase inhibitor simvastatinAngiogenesisPKBFactor treatmentPhosphorylationReductase inhibitor simvastatinApoptosisReconstitution of an Endothelial Nitric-oxide Synthase (eNOS), hsp90, and Caveolin-1 Complex in Vitro EVIDENCE THAT hsp90 FACILITATES CALMODULIN STIMULATED DISPLACEMENT OF eNOS FROM CAVEOLIN-1*
Gratton J, Fontana J, O'Connor D, Garcı́a-Cardeña G, McCabe T, Sessa W. Reconstitution of an Endothelial Nitric-oxide Synthase (eNOS), hsp90, and Caveolin-1 Complex in Vitro EVIDENCE THAT hsp90 FACILITATES CALMODULIN STIMULATED DISPLACEMENT OF eNOS FROM CAVEOLIN-1*. Journal Of Biological Chemistry 2000, 275: 22268-22272. PMID: 10781589, DOI: 10.1074/jbc.m001644200.Peer-Reviewed Original ResearchConceptsEndothelial nitric oxide synthaseAssociation of eNOSNitric oxide synthaseLung microvascular endothelial cellsCaveolin-1Microvascular endothelial cellsENOS enzymatic activityAction of CaMBovine lung microvascular endothelial cellsENOS functionCalcium-activated calmodulinConcentration of CaMShock protein 90Addition of CaMEndothelial cellsVitro EvidenceCav-1Protein 90AssociationPresence of Hsp90Enhanced Electron Flux and Reduced Calmodulin Dissociation May Explain “Calcium-independent” eNOS Activation by Phosphorylation*
McCabe T, Fulton D, Roman L, Sessa W. Enhanced Electron Flux and Reduced Calmodulin Dissociation May Explain “Calcium-independent” eNOS Activation by Phosphorylation*. Journal Of Biological Chemistry 2000, 275: 6123-6128. PMID: 10692402, DOI: 10.1074/jbc.275.9.6123.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCalciumCalmodulinCattleDimerizationEgtazic AcidElectronsEnzyme ActivationKineticsMutationNADH DehydrogenaseNADPNitric OxideNitric Oxide SynthaseNitric Oxide Synthase Type IIIPhosphorylationProtein Serine-Threonine KinasesProto-Oncogene ProteinsProto-Oncogene Proteins c-aktStatic ElectricityConceptsSerine 1179Reductase domainCalmodulin dissociationProtein kinase AktWild-type eNOSBovine endothelial nitric oxide synthaseEndothelial nitric oxide synthaseKinase AktRate-limiting stepReductase activityPhosphorylationENOS activationNOS functionPotential mechanismsAspartateENOS catalytic activityENOS activityCytochrome c reductionAktCalmodulinDomainProteinMutationsProductionActivity
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