2011
Splice isoform estrogen receptors as integral transmembrane proteins
Kim KH, Toomre D, Bender JR. Splice isoform estrogen receptors as integral transmembrane proteins. Molecular Biology Of The Cell 2011, 22: 4415-4423. PMID: 21937726, PMCID: PMC3216666, DOI: 10.1091/mbc.e11-05-0416.Peer-Reviewed Original ResearchConceptsSplice isoformsTotal internal reflection fluorescence microscopySteroid hormone receptorsIntegral transmembrane proteinN-terminal ectodomainReflection fluorescence microscopyHormone receptorsTransmembrane proteinPlasma membraneProtein structureHuman endothelial cellsLigand engagementPotential novel therapeutic targetER46Fluorescence microscopyNovel therapeutic targetEcliptic pHluorinActivation signalsEndothelial nitric oxide synthase activationEstrogen receptor αENOS activationReceptor αIsoformsTherapeutic targetNitric oxide synthase activation
2009
Membrane-initiated actions of estrogen on the endothelium
Kim KH, Bender JR. Membrane-initiated actions of estrogen on the endothelium. Molecular And Cellular Endocrinology 2009, 308: 3-8. PMID: 19549586, PMCID: PMC2701909, DOI: 10.1016/j.mce.2009.03.025.Peer-Reviewed Original ResearchConceptsEndothelial nitric oxide synthaseNumerous signal transduction cascadesSignal transduction cascadeNitric oxideEndothelial cellsNon-genomic actionsAction of estrogenNitric oxide synthaseCaveolar membranesEstrogen receptor alphaTransduction cascadeC-SrcN-terminusShort isoformHuman endothelial cellsRapid activationProduct nitric oxideVascular studiesOxide synthaseReceptor alphaEstrogenVascular structuresER46Favorable effectCritical role
2008
Vascular cell signaling by membrane estrogen receptors
Kim KH, Moriarty K, Bender JR. Vascular cell signaling by membrane estrogen receptors. Steroids 2008, 73: 864-869. PMID: 18325557, PMCID: PMC2519041, DOI: 10.1016/j.steroids.2008.01.008.Peer-Reviewed Original ResearchConceptsNumerous signal transduction cascadesEndothelial nitric oxide synthaseCaveolin-1 interactionSignal transduction cascadeEndothelial cellsNon-genomic actionsTranscriptional regulationPI3K/AktMembrane estrogen receptorsCaveolar membranesTransduction cascadeCell signalingC-SrcN-terminusHuman endothelial cellsRapid activationMolecular studiesConsequent activationVascular cellsNumerous animalsNitric oxideMultiple biological effectsEstrogen receptor alphaFavorable estrogenic effectsER46
2004
Vascular cell adhesion molecule-1-targeted detection of endothelial activation in human microvasculature
Sadeghi MM, Schechner JS, Krassilnikova S, Gharaei AA, Zhang J, Kirkiles-Smith N, Sinusas AJ, Zaret BL, Bender JR. Vascular cell adhesion molecule-1-targeted detection of endothelial activation in human microvasculature. Transplantation Proceedings 2004, 36: 1585-1591. PMID: 15251390, DOI: 10.1016/j.transproceed.2004.05.060.Peer-Reviewed Original ResearchConceptsChimeric human/mouse modelHuman/mouse modelHuman skin graftsEndothelial activationSkin graftsEndothelial cellsMouse modelIsotype-matched control antibodySCID/beige miceTumor necrosis factorEndothelial adhesion moleculesMurine VCAM-1Murine red blood cellsRed blood cellsHuman endothelial cellsControl antibodyInflammatory responseNecrosis factorBeige miceTc-99mVCAM-1Tissue vascularityMonoclonal antibodiesBlood cellsAdhesion molecules
2003
Plasma membrane localization and function of the estrogen receptor α variant (ER46) in human endothelial cells
Li L, Haynes MP, Bender JR. Plasma membrane localization and function of the estrogen receptor α variant (ER46) in human endothelial cells. Proceedings Of The National Academy Of Sciences Of The United States Of America 2003, 100: 4807-4812. PMID: 12682286, PMCID: PMC153637, DOI: 10.1073/pnas.0831079100.Peer-Reviewed Original ResearchMeSH KeywordsAlternative SplicingAnimalsBase SequenceCell LineCell MembraneCOS CellsEndothelium, VascularEstrogen Receptor alphaGenes, ReporterGenetic VariationHumansNitric Oxide SynthaseNitric Oxide Synthase Type IIIProtein Processing, Post-TranslationalReceptors, EstrogenRecombinant ProteinsRNA, MessengerSubcellular FractionsTranscriptional ActivationTransfectionConceptsPlasma membranePalmitoylation-dependent mannerPlasma membrane localizationInhibition of palmitoylationFull-length ER alphaReporter gene transactivationCOS-7 cellsEndothelial cell proteinsMembrane localizationAlternative splicingEstrogen receptor α variantsOestrogen receptor-alpha variantsN-terminusHuman endothelial cellsCell proteinsER46Synthase pathwayAcid labelingHy926 cellsNonendothelial cellsENOS activationENOS phosphorylationCellsEndothelial cellsMembrane
2002
Src Kinase Mediates Phosphatidylinositol 3-Kinase/Akt-dependent Rapid Endothelial Nitric-oxide Synthase Activation by Estrogen*
Haynes MP, Li L, Sinha D, Russell KS, Hisamoto K, Baron R, Collinge M, Sessa WC, Bender JR. Src Kinase Mediates Phosphatidylinositol 3-Kinase/Akt-dependent Rapid Endothelial Nitric-oxide Synthase Activation by Estrogen*. Journal Of Biological Chemistry 2002, 278: 2118-2123. PMID: 12431978, DOI: 10.1074/jbc.m210828200.Peer-Reviewed Original ResearchMeSH KeywordsAdenoviridaeAnimalsBlotting, WesternCell LineCells, CulturedElectrophoresis, Polyacrylamide GelEndoplasmic ReticulumEndothelium, VascularEnzyme ActivationEnzyme InhibitorsEstrogensHumansMiceMutationNitric OxideNitric Oxide SynthaseNitric Oxide Synthase Type IINitric Oxide Synthase Type IIIPhosphatidylinositol 3-KinasesPhosphorylationPrecipitin TestsProtein BindingProtein Serine-Threonine KinasesProto-Oncogene ProteinsProto-Oncogene Proteins c-aktReceptors, EstrogenSignal TransductionSrc-Family KinasesTime FactorsTransfectionTyrosineConceptsC-SrcPI3-kinaseAkt phosphorylationSrc kinaseUpstream regulatorKinase-dead c-SrcC-Src associationActive c-SrcC-Src phosphorylationMurine embryonic fibroblastsBasal Akt phosphorylationC-Src expressionCritical upstream regulatorEndothelial nitric oxide synthaseSrc familyActive AktEmbryonic fibroblastsComplex formation resultsEndothelial cellsHuman endothelial cellsAkt activationPhosphorylationKinaseAktPhosphatidylinositol
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 involvementHuman vascular endothelial cells contain membrane binding sites for estradiol, which mediate rapid intracellular signaling
Russell K, Haynes M, Sinha D, Clerisme E, Bender J. Human vascular endothelial cells contain membrane binding sites for estradiol, which mediate rapid intracellular signaling. Proceedings Of The National Academy Of Sciences Of The United States Of America 2000, 97: 5930-5935. PMID: 10823945, PMCID: PMC18536, DOI: 10.1073/pnas.97.11.5930.Peer-Reviewed Original ResearchMeSH KeywordsAntibodies, MonoclonalCell LineCell Membrane PermeabilityCells, CulturedCyclic GMPEndothelium, VascularEstradiolFlow CytometryHumansMAP Kinase Signaling SystemMitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3Mitogen-Activated Protein KinasesNitric OxideReceptors, EstrogenRecombinant Fusion ProteinsSerum Albumin, BovineSignal TransductionTime FactorsTransfectionConceptsHuman endothelial cellsEstrogen receptorEndothelial cellsMitogen-activated protein kinaseER antagonist ICIHuman vascular endothelial cellsMembrane estrogen receptorsMembrane-impermeant formVascular endothelial cellsRapid intracellularRapid nongenomic responsesAntagonist ICIVascular functionE2 treatmentAcute effectsERalpha antibodyCGMP productionCardiovascular systemNongenomic responsesCytometric analysisEstrogen inducesGuanylate cyclaseRapid effectsNO releaseEarly effects
1995
Lymphocyte adhesion-dependent calcium signaling in human endothelial cells.
Pfau S, Leitenberg D, Rinder H, Smith BR, Pardi R, Bender JR. Lymphocyte adhesion-dependent calcium signaling in human endothelial cells. Journal Of Cell Biology 1995, 128: 969-978. PMID: 7533170, PMCID: PMC2120392, DOI: 10.1083/jcb.128.5.969.Peer-Reviewed Original ResearchConceptsEC Ca2Endothelial cellsEC alterationsLymphocyte-endothelial interactionsNatural killer cellsImmune effector cellsTumor necrosis factorHuman umbilical vein endothelial cellsCytosolic free calcium changesUmbilical vein endothelial cellsVascular endothelial cellsHuman umbilical vein ECsAllogeneic CD3Lymphocyte subsetsVein endothelial cellsHuman endothelial cellsNK cellsEffector cellsKiller cellsVascular toneInflammatory responseNecrosis factorSecond messenger pathwaysExtracellular influxCytokine activation