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
2021
Characterization of a Novel Caveolin Modulator That Reduces Vascular Permeability and Ocular Inflammation
Bernatchez PN, Tao B, Bradshaw RA, Eveleth D, Sessa WC. Characterization of a Novel Caveolin Modulator That Reduces Vascular Permeability and Ocular Inflammation. Translational Vision Science & Technology 2021, 10: 21-21. PMID: 34111267, PMCID: PMC8132009, DOI: 10.1167/tvst.10.6.21.Peer-Reviewed Original ResearchConceptsOcular inflammationCell-permeable peptideRetinal damageVascular permeabilityModel of uveitisVascular endothelial growth factorNitric oxide releaseEndothelial growth factorNovel cell-permeable peptideEndothelial cell signalingVascular leakageClinical developmentInflammationOxide releaseEndothelial cellsNO releaseGrowth factorUveitisVEGFDistinct assaysPhage display technologyPresent studyVivoCell signalingPeptides
2001
Akt 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
Vascular Endothelial Growth Factor–Stimulated Actin Reorganization and Migration of Endothelial Cells Is Regulated via the Serine/Threonine Kinase Akt
Morales-Ruiz M, Fulton D, Sowa G, Languino L, Fujio Y, Walsh K, Sessa W. Vascular Endothelial Growth Factor–Stimulated Actin Reorganization and Migration of Endothelial Cells Is Regulated via the Serine/Threonine Kinase Akt. Circulation Research 2000, 86: 892-896. PMID: 10785512, DOI: 10.1161/01.res.86.8.892.Peer-Reviewed Original ResearchConceptsSignal transduction mechanismsCell migrationActin reorganizationActive AktMyr-AktSerine/threonine kinase AktCell signal transduction mechanismsTransduction mechanismsThreonine kinase AktVascular endothelial growth factorDominant-negative AktDistinct signal transduction mechanismsBovine lung microvascular endothelial cellsEndothelial cellsAbsence of VEGFActin cytoskeletonGrowth factorMicrovascular endothelial cellsKinase AktActin rearrangementStress fibersF-actinCell locomotionEndothelial growth factorEndothelial cell proliferation
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
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