2017
mTOR (Mechanistic Target of Rapamycin) Inhibition Decreases Mechanosignaling, Collagen Accumulation, and Stiffening of the Thoracic Aorta in Elastin-Deficient Mice
Jiao Y, Li G, Li Q, Ali R, Qin L, Li W, Qyang Y, Greif DM, Geirsson A, Humphrey JD, Tellides G. mTOR (Mechanistic Target of Rapamycin) Inhibition Decreases Mechanosignaling, Collagen Accumulation, and Stiffening of the Thoracic Aorta in Elastin-Deficient Mice. Arteriosclerosis Thrombosis And Vascular Biology 2017, 37: 1657-1666. PMID: 28751568, PMCID: PMC5574180, DOI: 10.1161/atvbaha.117.309653.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAorta, ThoracicAortic DiseasesCell ProliferationCollagenElastinEverolimusFocal Adhesion Kinase 1Genetic Predisposition to DiseaseHumansImatinib MesylateMechanistic Target of Rapamycin Complex 1Mechanistic Target of Rapamycin Complex 2Mechanotransduction, CellularMice, Inbred C57BLMice, KnockoutMultiprotein ComplexesMuscle, Smooth, VascularPhenotypePhosphorylationProtein Kinase InhibitorsSirolimusTime FactorsTOR Serine-Threonine KinasesVascular StiffnessWilliams SyndromeConceptsElastin deficiencyCollagen accumulationArterial phenotypeNull miceGrowth factorSmooth muscle cell proliferationMuscle cell proliferationEarly postnatal deathInhibition of mTORAortic fibrosisAortic obstructionMedial thickeningAortic stiffeningNeonatal deathLuminal stenosisPharmacological blockadeAbsence of elastinThoracic aortaTherapeutic benefitJuvenile micePostnatal deathMTOR inhibitionAortaHeterozygous lossMice
2004
Calmodulin phosphorylation and modulation of endothelial nitric oxide synthase catalysis
Greif DM, Sacks DB, Michel T. Calmodulin phosphorylation and modulation of endothelial nitric oxide synthase catalysis. Proceedings Of The National Academy Of Sciences Of The United States Of America 2004, 101: 1165-1170. PMID: 14736917, PMCID: PMC337024, DOI: 10.1073/pnas.0306377101.Peer-Reviewed Original ResearchConceptsPhosphorylation of CaMBovine aortic endothelial cellsCaM phosphorylationCaM mutantsCalcium regulatory protein calmodulinBiosynthetic labelingRegulation of eNOSProtein kinase pathwayEndothelial NO synthaseSer-81Regulatory protein calmodulinKinase CK2Kinase pathwayEndothelial cellsCK2Protein calmodulinMutantsCalmodulin phosphorylationPhosphorylationAortic endothelial cellsPhenyl-SepharoseUnique pathwayENOS activationMutant CaMPathway
2002
Site-Specific Dephosphorylation of Endothelial Nitric Oxide Synthase by Protein Phosphatase 2A: Evidence for Crosstalk between Phosphorylation Sites †
Greif DM, Kou R, Michel T. Site-Specific Dephosphorylation of Endothelial Nitric Oxide Synthase by Protein Phosphatase 2A: Evidence for Crosstalk between Phosphorylation Sites †. Biochemistry 2002, 41: 15845-15853. PMID: 12501214, DOI: 10.1021/bi026732g.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCattleCell LineCOS CellsEnzyme ActivationEnzyme InhibitorsMarine ToxinsMutagenesis, Site-DirectedNitric Oxide SynthaseNitric Oxide Synthase Type IIIOkadaic AcidOxazolesPhosphatesPhosphoprotein PhosphatasesPhosphorus RadioisotopesPhosphorylationProtein Phosphatase 2SerineSignal TransductionThreonineTransfectionConceptsProtein phosphatase 2ASerine 116Bovine aortic endothelial cellsCOS-7 cellsENOS dephosphorylationENOS mutantPhosphatase 2ASerine 1179Phosphorylation sitesThreonine 497Calcium/calmodulin-dependent enzymesInhibitor of PP2ASite-specific dephosphorylationProtein kinase pathwayWild-type eNOSEnzyme activityNitric oxide-dependent signaling pathwaysCalmodulin-dependent enzymesProtein phosphatasePosttranslational modificationsEpitope tagENOS phosphorylationKinase pathwayEndothelial cellsRecombinant proteinsDephosphorylation of Endothelial Nitric-oxide Synthase by Vascular Endothelial Growth Factor IMPLICATIONS FOR THE VASCULAR RESPONSES TO CYCLOSPORIN A*
Kou R, Greif D, Michel T. Dephosphorylation of Endothelial Nitric-oxide Synthase by Vascular Endothelial Growth Factor IMPLICATIONS FOR THE VASCULAR RESPONSES TO CYCLOSPORIN A*. Journal Of Biological Chemistry 2002, 277: 29669-29673. PMID: 12050171, DOI: 10.1074/jbc.m204519200.Peer-Reviewed Original ResearchConceptsENOS dephosphorylationSerine 116MAP kinase pathway inhibitor U0126Protein phosphatase pathwaysPhosphorylation-deficient mutantDependent protein phosphatasePhosphorylation state-specific antibodiesWild-type enzymeVascular endothelial growth factorProtein kinase C inhibitor calphostinPathway inhibitor U0126Activation of calcineurinProtein phosphataseInhibitor of calcineurinPhosphatase pathwaysENOS agonistsProtein kinaseEndothelial cellsAlanine residuesDephosphorylationDependent enzymesInhibitor U0126Dephosphorylation of eNOSCultured endothelial cellsEnzyme activity