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 ResearchConceptsPhosphorylation 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
2007
Regulation of Caveolin‐2 Phosphorylation at Serines 23 and 36
Sowa G, Sessa W. Regulation of Caveolin‐2 Phosphorylation at Serines 23 and 36. The FASEB Journal 2007, 21: a1424-a1424. DOI: 10.1096/fasebj.21.6.a1424-b.Peer-Reviewed Original ResearchLipid rafts/caveolaeSerine 36 phosphorylationRafts/caveolaeSerine 23Cav-2Serine phosphorylationCav-1Phospho-specific antibodiesSubcellular fractionation dataSubcellular fractionation techniquesN-terminal serineEndothelial cellsCaveolar compartmentCaveolae assemblyLipid raftsSubcellular locationRegulated processSerine 36Caveolin-2Human endothelial cellsAdenoviral expressionIntracellular compartmentsPhosphorylationCaveolaeResidues 23
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 chemotaxisTransactivationPhosphorylationGPCRsChemotaxisActivationMutantsSphingosine 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 involvementThe 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 simvastatinApoptosisEnhanced 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
1999
Regulation of endothelium-derived nitric oxide production by the protein kinase Akt
Fulton D, Gratton J, McCabe T, Fontana J, Fujio Y, Walsh K, Franke T, Papapetropoulos A, Sessa W. Regulation of endothelium-derived nitric oxide production by the protein kinase Akt. Nature 1999, 399: 597-601. PMID: 10376602, PMCID: PMC3637917, DOI: 10.1038/21218.Peer-Reviewed Original ResearchConceptsProtein kinase AktKinase AktSerine/threonine protein kinase AktMutant eNOSRole of phosphorylationEndothelial nitric oxide synthaseSerine 1179Akt substrateSignal transductionGene transferAktAdenovirus-mediated gene transferPhosphorylationGrowth factorVascular endothelial growth factorEndothelial cellsRegulationSynthase isoformsEndothelial growth factorNitric oxide productionTransductionVascular remodellingOxide productionIsoformsProduction
1996
Endothelial Nitric Oxide Synthase Is Regulated by Tyrosine Phosphorylation and Interacts with Caveolin-1*
García-Cardeña G, Fan R, Stern D, Liu J, Sessa W. Endothelial Nitric Oxide Synthase Is Regulated by Tyrosine Phosphorylation and Interacts with Caveolin-1*. Journal Of Biological Chemistry 1996, 271: 27237-27240. PMID: 8910295, DOI: 10.1074/jbc.271.44.27237.Peer-Reviewed Original ResearchConceptsNovel regulatory mechanismTyrosine phosphorylationCaveolin-1Bovine aortic endothelial cellsRegulatory mechanismsProtein tyrosine phosphatase inhibitorCaveolin-interacting proteinsPhosphoamino acid analysisTyrosine phosphatase inhibitorTreatment of BAECBovine lung microvascular endothelial cellsEndothelial nitric oxide synthaseSubcellular traffickingPhosphatase inhibitorCoat proteinEndothelial cellsMetabolic labelingSodium orthovanadatePhosphorylationCaveolaeAortic endothelial cellsLung microvascular endothelial cellsProteinAcid analysisImmunoprecipitation