2023
An optogenetic-phosphoproteomic study reveals dynamic Akt1 signaling profiles in endothelial cells
Zhou W, Li W, Wang S, Salovska B, Hu Z, Tao B, Di Y, Punyamurtula U, Turk B, Sessa W, Liu Y. An optogenetic-phosphoproteomic study reveals dynamic Akt1 signaling profiles in endothelial cells. Nature Communications 2023, 14: 3803. PMID: 37365174, PMCID: PMC10293293, DOI: 10.1038/s41467-023-39514-1.Peer-Reviewed Original ResearchMeSH KeywordsEndothelial CellsHumansOptogeneticsPhosphorylationProtein Serine-Threonine KinasesProto-Oncogene Proteins c-aktSignal TransductionConceptsPhosphorylation sitesSerine/threonine kinase AktMass spectrometry-based phosphoproteomicsThreonine kinase AktAkt-dependent phosphorylationAberrant Akt activationEndothelial cellsKinase substrateKinase AktCell signalingPhosphorylation profilePhenotypic outcomesDownstream signalingAkt activationAkt1 phosphorylationHuman diseasesSystem-level analysisAKT1Vascular endothelial cellsRich resourcePhosphorylationSignalingGrowth factorAktCells
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
Membrane Estrogen Receptor Engagement Activates Endothelial Nitric Oxide Synthase via the PI3-Kinase–Akt Pathway in Human Endothelial Cells
Haynes M, Sinha D, Russell K, Collinge M, Fulton D, Morales-Ruiz M, Sessa W, Bender J. Membrane Estrogen Receptor Engagement Activates Endothelial Nitric Oxide Synthase via the PI3-Kinase–Akt Pathway in Human Endothelial Cells. Circulation Research 2000, 87: 677-682. PMID: 11029403, DOI: 10.1161/01.res.87.8.677.Peer-Reviewed Original ResearchMeSH KeywordsAdenoviridaeBinding SitesCell MembraneCells, CulturedChromonesEndothelium, VascularEnzyme InhibitorsEstradiolGenes, DominantHumansMorpholinesNitric OxideNitric Oxide SynthaseNitric Oxide Synthase Type IIIPhosphatidylinositol 3-KinasesPhosphoinositide-3 Kinase InhibitorsPhosphorylationProtein Serine-Threonine KinasesProto-Oncogene ProteinsProto-Oncogene Proteins c-aktReceptors, EstrogenSerum Albumin, BovineSignal TransductionTransduction, GeneticConceptsPI3-kinaseKinase-Akt pathwayDominant-negative AktPI3-kinase inhibitorRapid eNOS phosphorylationRapid Akt phosphorylationActivation of eNOSAkt-dependent pathwayEndothelial nitric oxide synthaseAkt substratePhosphatidylinositol 3ENOS phosphorylationCritical residuesSerine 473Human endothelial cellsEstrogen receptor antagonist ICI 182Cell membrane sitesHuman endothelial cell lineAkt pathwayAkt phosphorylationPhosphorylationReceptor engagementEndothelial cell lineActivation eventsFunctional involvementAcute modulation of endothelial Akt/PKB activity alters nitric oxide–dependent vasomotor activity in vivo
Luo Z, Fujio Y, Kureishi Y, Rudic R, Daumerie G, Fulton D, Sessa W, Walsh K. Acute modulation of endothelial Akt/PKB activity alters nitric oxide–dependent vasomotor activity in vivo. Journal Of Clinical Investigation 2000, 106: 493-499. PMID: 10953024, PMCID: PMC380252, DOI: 10.1172/jci9419.Peer-Reviewed Original ResearchConceptsDN-AktEndothelial cell nitric oxide synthaseMyr-AktSerine/threonine protein kinase AktProtein kinase AktDominant-negative AktNitric oxideVasomotor toneFemoral arteryAkt functionReplication-defective adenoviral constructKinase AktActive AktEndothelium-dependent vasodilatationKey regulatorEndothelium-independent vasodilatorEndothelium-dependent vasomotionRabbit femoral artery modelNitric oxide synthaseAorta ex vivoImportant regulatorGene transferDoppler flow measurementsAktENOS inhibitorEnhanced 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 reductionAktCalmodulinDomainProteinMutationsProductionActivityAngiopoietin-1 Inhibits Endothelial Cell Apoptosis via the Akt/Survivin Pathway*
Papapetropoulos A, Fulton D, Mahboubi K, Kalb R, O'Connor D, Li F, Altieri D, Sessa W. Angiopoietin-1 Inhibits Endothelial Cell Apoptosis via the Akt/Survivin Pathway*. Journal Of Biological Chemistry 2000, 275: 9102-9105. PMID: 10734041, DOI: 10.1074/jbc.275.13.9102.Peer-Reviewed Original ResearchMeSH KeywordsAngiopoietin-1AnimalsApoptosisCattleCells, CulturedEndothelium, VascularFlow CytometryInhibitor of Apoptosis ProteinsMembrane GlycoproteinsMicrotubule-Associated ProteinsNeoplasm ProteinsPhosphorylationProtein Serine-Threonine KinasesProteinsProto-Oncogene ProteinsProto-Oncogene Proteins c-aktSurvivinConceptsAkt/survivin pathwaySerine-threonine kinaseDeath-inducing stimuliPost-natal angiogenesisDominant-negative survivinEndothelial cellsEndothelial cell survivalAnti-apoptotic pathwaysSurvival machineryEndothelial cell apoptosisSurvivin pathwayApoptosis inhibitorCell survivalCell apoptosisVascular stabilizationAktSurvivinTie-2 receptorAngiogenic responseApoptosisCellsPathwayAngiogenesisMorphogenesisKinase