2024
Latrophilin-2 mediates fluid shear stress mechanotransduction at endothelial junctions
Tanaka K, Chen M, Prendergast A, Zhuang Z, Nasiri A, Joshi D, Hintzen J, Chung M, Kumar A, Mani A, Koleske A, Crawford J, Nicoli S, Schwartz M. Latrophilin-2 mediates fluid shear stress mechanotransduction at endothelial junctions. The EMBO Journal 2024, 43: 3175-3191. PMID: 38886581, PMCID: PMC11294477, DOI: 10.1038/s44318-024-00142-0.Peer-Reviewed Original ResearchLatrophilin-2Affinity purification methodCell-cell junctionsHuman genetic dataPECAM-1SiRNA screenGenetic dataEndothelial cell response to fluid shear stressGA proteinsDownstream eventsEndothelial-specific knockoutG-proteinActivity assayShear stress mechanotransductionPlexin-D1Endothelial signalingJunctional complexesPurification methodVE-cadherinResponse to fluid shear stressVascular developmentGA residuesEndothelial junctionsGPCRsVEGF receptors
2017
VE-Cadherin Phosphorylation Regulates Endothelial Fluid Shear Stress Responses through the Polarity Protein LGN
Conway DE, Coon BG, Budatha M, Arsenovic PT, Orsenigo F, Wessel F, Zhang J, Zhuang Z, Dejana E, Vestweber D, Schwartz MA. VE-Cadherin Phosphorylation Regulates Endothelial Fluid Shear Stress Responses through the Polarity Protein LGN. Current Biology 2017, 27: 2219-2225.e5. PMID: 28712573, PMCID: PMC5667920, DOI: 10.1016/j.cub.2017.06.020.Peer-Reviewed Original ResearchConceptsSrc family kinasesProtein LGNCytoplasmic tyrosinesVE-cadherinVascular endothelial growth factor receptorVE-cadherin functionJunctional complexesRespective cytoplasmic domainsBlood vessel developmentVE-cadherin phosphorylationTransduce forcesTransduce signalsCytoplasmic domainFamily kinasesBlood vessel remodelingGrowth factor receptorVEGFR activationPECAM-1Stress responseComplex consistingFluid shear stressVessel developmentFlow-dependent vascular remodelingSpecific poolPhosphorylation
2016
Endothelial basement membrane laminin 511 is essential for shear stress response
Di Russo J, Luik A, Yousif L, Budny S, Oberleithner H, Hofschröer V, Klingauf J, van Bavel E, Bakker E, Hellstrand P, Bhattachariya A, Albinsson S, Pincet F, Hallmann R, Sorokin L. Endothelial basement membrane laminin 511 is essential for shear stress response. The EMBO Journal 2016, 36: 183-201. PMID: 27940654, PMCID: PMC5239996, DOI: 10.15252/embj.201694756.Peer-Reviewed Original ResearchConceptsCell-cell adhesion strengthLaminin-511Junctional complexesVE-cadherinIntegrin-mediated interactionsEndothelial basement membrane componentVinculin-positive focal adhesionsCatenin associationFocal adhesionsStress responseCell junctionsMembrane componentsBasement membrane componentsBasement membraneArterial endotheliumCortical stiffnessMechanotransductionPECAM-1Firm anchorageEndothelial basement membraneJunctional associationMembraneConsiderable informationComplexesAdhesion
2015
Intramembrane binding of VE-cadherin to VEGFR2 and VEGFR3 assembles the endothelial mechanosensory complex
Coon BG, Baeyens N, Han J, Budatha M, Ross TD, Fang JS, Yun S, Thomas JL, Schwartz MA. Intramembrane binding of VE-cadherin to VEGFR2 and VEGFR3 assembles the endothelial mechanosensory complex. Journal Of Cell Biology 2015, 208: 975-986. PMID: 25800053, PMCID: PMC4384728, DOI: 10.1083/jcb.201408103.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, CDCadherinsCell MovementCells, CulturedEndothelium, VascularHEK293 CellsHuman Umbilical Vein Endothelial CellsHumansMechanotransduction, CellularMiceMice, Inbred C57BLNeovascularization, PhysiologicPlaque, AtheroscleroticPlatelet Endothelial Cell Adhesion Molecule-1Protein Structure, TertiaryRNA InterferenceRNA, Small InterferingStress, MechanicalStress, PhysiologicalVascular Endothelial Growth Factor Receptor-2Vascular Endothelial Growth Factor Receptor-3
2013
Fluid Shear Stress on Endothelial Cells Modulates Mechanical Tension across VE-Cadherin and PECAM-1
Conway DE, Breckenridge MT, Hinde E, Gratton E, Chen CS, Schwartz MA. Fluid Shear Stress on Endothelial Cells Modulates Mechanical Tension across VE-Cadherin and PECAM-1. Current Biology 2013, 23: 1024-1030. PMID: 23684974, PMCID: PMC3676707, DOI: 10.1016/j.cub.2013.04.049.Peer-Reviewed Original ResearchConceptsFluid shear stressVE-cadherinCell-cell junctionsPECAM-1Junctional tensionCytoskeletal remodelingVascular morphogenesisGene expressionComplex consistingCells triggersFlow-dependent vascular remodelingIon channelsFRET measurementsEndothelial cells triggersMechanical tensionNormal vascular functionTension sensorDetectable tensionEC responseStatic cultureJunctional receptorsRemodelingCytoskeletonMorphogenesisVascular remodeling
2012
Lessons from the endothelial junctional mechanosensory complex
Conway D, Schwartz MA. Lessons from the endothelial junctional mechanosensory complex. F1000 Biology Reports 2012, 4: 1. PMID: 22238515, PMCID: PMC3251317, DOI: 10.3410/b4-1.Peer-Reviewed Original Research
2010
Atheroprone Hemodynamics Regulate Fibronectin Deposition to Create Positive Feedback That Sustains Endothelial Inflammation
Feaver RE, Gelfand BD, Wang C, Schwartz MA, Blackman BR. Atheroprone Hemodynamics Regulate Fibronectin Deposition to Create Positive Feedback That Sustains Endothelial Inflammation. Circulation Research 2010, 106: 1703-1711. PMID: 20378855, PMCID: PMC2891748, DOI: 10.1161/circresaha.109.216283.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAortic DiseasesApolipoproteins EAtherosclerosisCells, CulturedDisease Models, AnimalEndothelium, VascularFeedback, PhysiologicalFibronectinsHemodynamicsHumansInflammationMechanotransduction, CellularMiceMice, Inbred C57BLMice, KnockoutNF-kappa BPlatelet Endothelial Cell Adhesion Molecule-1Pulsatile FlowRegional Blood FlowRNA InterferenceStress, MechanicalTime FactorsTransfectionUp-RegulationConceptsFN depositionAtheroprone flowPECAM-1FN expressionTranscription factor NF-kappaB.Platelet endothelial cell adhesion moleculeNF-kappaB activationNF-kappaB activityAtheroprone hemodynamicsHuman endothelial cellsEndothelial inflammationProinflammatory phenotypeAortic archInduction of fibronectinCarotid arteryCell adhesion moleculeExogenous fibronectinInflammatory signalingFN accumulationNF-kappaBSustained increaseNF-kappaB.Nuclear factorTransient increaseEndothelial cellsInsights into Monocyte-Driven Osteoclastogenesis and Its Link with Hematopoiesis: Regulatory Roles of PECAM-1 (CD31) and SHP-1
Wu Y, Madri J. Insights into Monocyte-Driven Osteoclastogenesis and Its Link with Hematopoiesis: Regulatory Roles of PECAM-1 (CD31) and SHP-1. Critical Reviews In Immunology 2010, 30: 423-433. PMID: 21083524, DOI: 10.1615/critrevimmunol.v30.i5.20.Peer-Reviewed Original Research
2009
Bone Marrow Monocyte PECAM-1 Deficiency Elicits Increased Osteoclastogenesis Resulting in Trabecular Bone Loss
Wu Y, Tworkoski K, Michaud M, Madri JA. Bone Marrow Monocyte PECAM-1 Deficiency Elicits Increased Osteoclastogenesis Resulting in Trabecular Bone Loss. The Journal Of Immunology 2009, 182: 2672-2679. PMID: 19234161, DOI: 10.4049/jimmunol.0802398.Peer-Reviewed Original ResearchMeSH KeywordsAgingAnimalsBone Marrow CellsBone ResorptionCell DifferentiationCells, CulturedDown-RegulationFemaleIntracellular Signaling Peptides and ProteinsMiceMice, KnockoutMonocytesOsteoclastsOsteogenesisPhosphorylationPlatelet Endothelial Cell Adhesion Molecule-1Protein Tyrosine Phosphatase, Non-Receptor Type 6Protein-Tyrosine KinasesSyk KinaseZAP-70 Protein-Tyrosine KinaseConceptsOsteoclast-like cellsKO miceBone marrowPECAM-1-null miceTrabecular bone lossPECAM-1Trabecular bone volumeSize of osteoclastsNF-kappaB ligandOsteoclast precursor culturesSHP-1 interactionsNumber of trabeculaeWT miceBM monocytesBone lossBone resorptionReceptor activatorBone volumeSHP-1Precursor culturesNull miceMiceLong bonesSyk kinaseFurther studies
2008
Endothelial Cell PECAM-1 Promotes Atherosclerotic Lesions in Areas of Disturbed Flow in ApoE-Deficient Mice
Harry BL, Sanders JM, Feaver RE, Lansey M, Deem TL, Zarbock A, Bruce AC, Pryor AW, Gelfand BD, Blackman BR, Schwartz MA, Ley K. Endothelial Cell PECAM-1 Promotes Atherosclerotic Lesions in Areas of Disturbed Flow in ApoE-Deficient Mice. Arteriosclerosis Thrombosis And Vascular Biology 2008, 28: 2003-2008. PMID: 18688018, PMCID: PMC2651147, DOI: 10.1161/atvbaha.108.164707.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAorta, AbdominalAorta, ThoracicApolipoproteins EAtherosclerosisBone Marrow CellsBone Marrow TransplantationCells, CulturedDietary FatsDisease Models, AnimalDisease ProgressionEndothelial CellsHumansMacrophagesMiceMice, Inbred C57BLMice, KnockoutNF-kappa BPlatelet Endothelial Cell Adhesion Molecule-1Regional Blood FlowRNA InterferenceRNA, Small InterferingStress, MechanicalVascular Cell Adhesion Molecule-1ConceptsEndothelial PECAM-1PECAM-1Aortic archAbdominal aortaNF-kappaBVascular cell adhesion molecule-1 expressionCell adhesion molecule-1 expressionAdhesion molecule-1 expressionCell adhesion molecule-1ApoE-deficient miceAtherosclerotic lesion sizeBone marrow transplantationAtherosclerotic lesion formationMolecule-1 expressionVCAM-1 expressionAdhesion molecule-1Endothelial cell adhesion molecule-1NF-kappaB activityNuclear NF-kappaBDisturbed flowMarrow transplantationMacrophage infiltrationLesser curvatureWestern dietDeficient mice
2006
PECAM‐1 modulates thrombin‐induced tissue factor expression on endothelial cells
Zhang JJ, Kelm RJ, Biswas P, Kashgarian M, Madri JA. PECAM‐1 modulates thrombin‐induced tissue factor expression on endothelial cells. Journal Of Cellular Physiology 2006, 210: 527-537. PMID: 17111362, DOI: 10.1002/jcp.20908.Peer-Reviewed Original ResearchMeSH KeywordsActive Transport, Cell NucleusAnimalsApoptosisBlood CoagulationCells, CulturedDisease Models, AnimalDown-RegulationEarly Growth Response Protein 1Endothelial CellsFibrinHumansKidneyMaleMAP Kinase Signaling SystemMiceMice, Inbred C57BLMice, KnockoutOligodeoxyribonucleotides, AntisensePlatelet Endothelial Cell Adhesion Molecule-1Receptor, PAR-1Reperfusion InjuryRNA, MessengerThrombinThromboplastinThrombosisConceptsTissue factor expressionHuman umbilical vein endothelial cellsFactor expressionPECAM-1TF inductionEndothelial cellsP38 phosphorylationCell adhesion molecule-1Transient renal ischemiaThrombin receptor PAR-1PAR-1 antagonistsPertussis toxin inhibitionAdhesion molecule-1Endothelial cell adhesion molecule-1Receptor PAR-1PI3K-Akt phosphorylationGalphai/o subunitsPECAM-1 expressionRho-kinase activityUmbilical vein endothelial cellsVein endothelial cellsRenal ischemiaEgr-1 expressionFibrin depositionPlatelet functionPECAM-1 Affects GSK-3β-Mediated β-Catenin Phosphorylation and Degradation
Biswas P, Canosa S, Schoenfeld D, Schoenfeld J, Li P, Cheas LC, Zhang J, Cordova A, Sumpio B, Madri JA. PECAM-1 Affects GSK-3β-Mediated β-Catenin Phosphorylation and Degradation. American Journal Of Pathology 2006, 169: 314-324. PMID: 16816383, PMCID: PMC1698776, DOI: 10.2353/ajpath.2006.051112.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsbeta CateninBlotting, WesternCapillary PermeabilityCells, CulturedEndothelial CellsFluorescent Antibody TechniqueGlycogen Synthase Kinase 3Glycogen Synthase Kinase 3 betaHistamineHistamine AgentsHumansMiceModels, BiologicalPhosphatidylinositol 3-KinasesPhosphorylationPlatelet Endothelial Cell Adhesion Molecule-1Proto-Oncogene Proteins c-aktReceptors, HistamineSignal TransductionConceptsAdherens junctionsSerine phosphorylationSrc homology 2 domainBeta-catenin expression levelsAdherens junction componentsSerine phosphorylation levelEndothelial cellsΒ-catenin phosphorylationPECAM-1Cell biological responsesCytoplasmic domainSHP-2Proteosomal degradationGSK-3betaDynamic regulatorJunction componentsPhosphorylation levelsPhosphorylationEndothelial cell adhesion molecule-1Expression levelsGSK-3βBiological responsesEndothelial barrier permeabilityMice exhibitCell adhesion molecule-1A mechanosensory complex that mediates the endothelial cell response to fluid shear stress
Tzima E, Irani‐Tehrani M, Kiosses W, Dejana E, Schultz D, Engelhardt B, Cao G, DeLisser H, Schwartz M. A mechanosensory complex that mediates the endothelial cell response to fluid shear stress. The FASEB Journal 2006, 20: a1378-a1378. DOI: 10.1096/fasebj.20.5.a1378-c.Peer-Reviewed Original ResearchPECAM-1-null miceDownstream inflammatory genesPECAM-1VE-cadherinDevelopment of atherosclerosisICAM-1 expressionNF-kB activationInitiation of atherosclerosisBlood pressureVascular remodelingHigh-affinity stateInflammatory genesNF-κBCell responsesEndothelial cell responsesNull miceMechanosensory complexIntegrin activationAffinity stateAtherosclerosisVEGFR2Heterologous cellsPathway upstreamActivationSrc family kinasesPECAM‐1: a multi‐faceted regulator of megakaryocytopoiesis
Wu Y, Madri J. PECAM‐1: a multi‐faceted regulator of megakaryocytopoiesis. The FASEB Journal 2006, 20: a633-a633. DOI: 10.1096/fasebj.20.4.a633-c.Peer-Reviewed Original ResearchNull animalsMulti-faceted regulatorAltered localizationActin filament organizationProgenitor cellsDifferentiation of megakaryocytesCommitted progenitor cellsEndothelial cell monolayersQuiescent G0 phaseHematopoietic stem cellsSHP-2Progenitor populationsMarrow progenitor cellsSHP-1Filament organizationPECAM-1Mature megakaryocytesCell monolayersFGF-4Colony formation potentialStem cellsAbnormal megakaryocytopoiesisMegakaryocyte adhesionG0 phaseLSK population
2005
Neutrophils Lacking Platelet-Endothelial Cell Adhesion Molecule-1 Exhibit Loss of Directionality and Motility in CXCR2-Mediated Chemotaxis
Wu Y, Stabach P, Michaud M, Madri JA. Neutrophils Lacking Platelet-Endothelial Cell Adhesion Molecule-1 Exhibit Loss of Directionality and Motility in CXCR2-Mediated Chemotaxis. The Journal Of Immunology 2005, 175: 3484-3491. PMID: 16148090, DOI: 10.4049/jimmunol.175.6.3484.Peer-Reviewed Original ResearchMeSH KeywordsActinsAnimalsCell ShapeChemokine CXCL1ChemokinesChemokines, CXCChemotaxis, LeukocyteCytokinesInterleukin-8Intracellular Signaling Peptides and ProteinsMiceMice, KnockoutNeutrophilsPlatelet Endothelial Cell Adhesion Molecule-1Protein Phosphatase 1Protein Tyrosine Phosphatase, Non-Receptor Type 6Protein Tyrosine PhosphatasesReceptors, Interleukin-8BConceptsCell motilitySrc homology 2 domainF-actinSHP-1 phosphatase activityWild-type neutrophilsF-actin polymerizationPhosphatase 1Time-lapse videomicroscopyPECAM-1Cytokine-induced mobilizationPhosphatase activityExhibit lossMurine neutrophilsMotilityChemotaxisZigmond chamberCellsPECAMLeading frontCytoskeletonMoesinIL-8FMLP gradientProteinActinA mechanosensory complex that mediates the endothelial cell response to fluid shear stress
Tzima E, Irani-Tehrani M, Kiosses WB, Dejana E, Schultz DA, Engelhardt B, Cao G, DeLisser H, Schwartz MA. A mechanosensory complex that mediates the endothelial cell response to fluid shear stress. Nature 2005, 437: 426-431. PMID: 16163360, DOI: 10.1038/nature03952.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, CDCadherinsCattleCell AdhesionCells, CulturedEndothelial CellsFemaleGene DeletionMechanotransduction, CellularMiceMice, KnockoutMultiprotein ComplexesNF-kappa BPlatelet Endothelial Cell Adhesion Molecule-1RatsStress, MechanicalVascular Endothelial Growth Factor Receptor-2ConceptsDownstream inflammatory genesPECAM-1 knockout miceVascular endothelial cell cadherinVascular remodellingHigh-affinity stateInflammatory genesNF-κBVascular homeostasisEndothelial cell responsesCell responsesMechanosensory complexPECAM-1Heterologous cellsPathway upstreamCardiac developmentIntegrin activationAtherogenesisMechanism of transductionPathwayMice
2003
PECAM-1 promotes β-catenin accumulation and stimulates endothelial cell proliferation
Biswas P, Canosa S, Schoenfeld J, Schoenfeld D, Tucker A, Madri JA. PECAM-1 promotes β-catenin accumulation and stimulates endothelial cell proliferation. Biochemical And Biophysical Research Communications 2003, 303: 212-218. PMID: 12646189, DOI: 10.1016/s0006-291x(03)00313-9.Peer-Reviewed Original ResearchMeSH KeywordsActinsAnimalsbeta CateninBlotting, WesternCell AdhesionCell DivisionCytoplasmCytoskeletal ProteinsEndotheliumFlow CytometryHumansLungMiceMice, KnockoutMicroscopy, FluorescencePlatelet Endothelial Cell Adhesion Molecule-1Precipitin TestsSignal TransductionTrans-ActivatorsTranscription, GeneticTransfectionConceptsPECAM-1-positive endothelial cellsBeta-catenin proteinCell proliferationEndothelial cellsPECAM-1Beta-catenin localizationCytoplasmic domainΒ-catenin accumulationFull-length PECAM-1Functional consequencesEndothelial cell proliferationCell membraneKnockout animalsAdhesion moleculesLess accumulationCellsAccumulationProliferative rateProliferationMembraneProteinBindsPlatelet–endothelial cell adhesion molecule-1 modulates endothelial migration through its immunoreceptor tyrosine-based inhibitory motif
Gratzinger D, Barreuther M, Madri JA. Platelet–endothelial cell adhesion molecule-1 modulates endothelial migration through its immunoreceptor tyrosine-based inhibitory motif. Biochemical And Biophysical Research Communications 2003, 301: 243-249. PMID: 12535670, DOI: 10.1016/s0006-291x(02)02982-0.Peer-Reviewed Original ResearchMeSH KeywordsAdherens JunctionsAmino Acid MotifsAnimalsCattleCell MovementCells, CulturedEndothelium, VascularEnzyme ActivationIntracellular Signaling Peptides and ProteinsMiceMice, KnockoutPhosphorylationPlatelet Endothelial Cell Adhesion Molecule-1Protein BindingProtein Tyrosine Phosphatase, Non-Receptor Type 11Protein Tyrosine PhosphatasesRecombinant Fusion ProteinsTyrosineConceptsSHP-2Tyrosine phosphatase SHP-2Endothelial migrationFocal contact componentsPlatelet endothelial cell adhesion molecule-1Phosphatase SHP-2Cell-cell junctionsImmunoreceptor tyrosine-based inhibitory motifCell-substrate adhesionFocal adhesion kinaseTyrosine-based inhibitory motifPECAM-1Endothelial cellsPECAM-1 phosphorylationSelective dephosphorylationAdhesion kinaseTyrosine phosphorylationAdhesion proteinsRecombinant proteinsCytoskeletal fractionCell adhesion molecule-1Coordinated migrationInhibitory motifPhosphorylationAdhesion molecule-1
2001
PECAM-1 Is a Modulator of STAT Family Member Phosphorylation and Localization: Lessons from a Transgenic Mouse
Ilan N, Cheung L, Miller S, Mohsenin A, Tucker A, Madri J. PECAM-1 Is a Modulator of STAT Family Member Phosphorylation and Localization: Lessons from a Transgenic Mouse. Developmental Biology 2001, 232: 219-232. PMID: 11254359, DOI: 10.1006/dbio.2001.0186.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell DivisionCell NucleusCells, CulturedDNA-Binding ProteinsEndothelium, VascularFemaleHumansMammary Glands, AnimalMiceMice, TransgenicMilk ProteinsMorphogenesisPhosphorylationPlatelet Endothelial Cell Adhesion Molecule-1Pulmonary AlveoliSTAT5 Transcription FactorTrans-ActivatorsTumor Suppressor ProteinsConceptsImmunoreceptor tyrosine activation motifMilk protein gene expressionPhosphorylation levelsSignal transduction pathwaysProtein gene expressionTyrosine activation motifTyrosine phosphorylation levelsPECAM-1Cell cycle progressionMammary gland developmentInduction of p21Cytoplasmic tailBranching morphogenesisTransduction pathwaysTransgenic miceActivation motifCell adhesion moleculeDuctal epithelial cell proliferationGene expressionCycle progressionGland developmentEpithelial cell proliferationDuctal branching morphogenesisCell proliferationVascular cellsPECAM‐1 shedding during apoptosis generates a membrane‐anchored truncated molecule with unique signaling characteristics
ILAN N, MOHSENIN A, CHEUNG L, MADRI J. PECAM‐1 shedding during apoptosis generates a membrane‐anchored truncated molecule with unique signaling characteristics. The FASEB Journal 2001, 15: 362-372. PMID: 11156952, DOI: 10.1096/fj.00-0372com.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid Chloromethyl KetonesAnimalsAntigens, CDApoptosisBlood PlateletsCaspasesCattleCell DivisionCell LineCell MembraneCells, CulturedColonic NeoplasmsCulture MediaDipeptidesEndothelium, VascularEnzyme InhibitorsHumansPlatelet Endothelial Cell Adhesion Molecule-1Sequence DeletionSignal TransductionTransfectionTumor Cells, CulturedUmbilical VeinsConceptsFull-length PECAM-1Signal transduction cascadeSignal transduction eventsCaspase-8 cleavageCell proliferationPECAM-1SW480 colon carcinoma cellsCaspase substratesSHP-2Transduction cascadeTransduction eventsGrowth factor receptorCell adhesion moleculeGene constructsCell surface moleculesColon carcinoma cellsSoluble proteinStable expressionCell deathCulture mediumMatrix metalloproteinaseCell surfaceJNK phosphorylationUnique functionFactor receptor
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