2021
Activation of Smad2/3 signaling by low fluid shear stress mediates artery inward remodeling
Deng H, Min E, Baeyens N, Coon BG, Hu R, Zhuang ZW, Chen M, Huang B, Afolabi T, Zarkada G, Acheampong A, McEntee K, Eichmann A, Liu F, Su B, Simons M, Schwartz MA. Activation of Smad2/3 signaling by low fluid shear stress mediates artery inward remodeling. Proceedings Of The National Academy Of Sciences Of The United States Of America 2021, 118: e2105339118. PMID: 34504019, PMCID: PMC8449390, DOI: 10.1073/pnas.2105339118.Peer-Reviewed Original ResearchConceptsLow fluid shear stressFluid shear stressNuclear translocationSmad linker regionTransmembrane protein Neuropilin-1Target gene expressionCyclin-dependent kinasesBone morphogenetic proteinEC-specific deletionSmad2/3 nuclear translocationNuclear localizationHigh fluid shear stressLinker regionMorphogenetic proteinsGene expressionRegulatory mechanismsActivation of Smad2/3Receptor ALK5Smad2/3 phosphorylationTranslocationCell sensingEndothelial cell (EC) sensingPhosphorylationALK5Smad2/3
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: 2727. PMID: 28898639, PMCID: PMC5752114, DOI: 10.1016/j.cub.2017.08.064.Peer-Reviewed Original ResearchVE-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
2009
Focal adhesion kinase modulates activation of NF-κB by flow in endothelial cells
Petzold T, Orr AW, Hahn C, Jhaveri KA, Parsons JT, Schwartz MA. Focal adhesion kinase modulates activation of NF-κB by flow in endothelial cells. American Journal Of Physiology - Cell Physiology 2009, 297: c814-c822. PMID: 19587216, PMCID: PMC2770750, DOI: 10.1152/ajpcell.00226.2009.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell NucleusCells, CulturedEndothelial CellsEndothelium, VascularFocal Adhesion Protein-Tyrosine KinasesHydrogen PeroxideI-kappa B KinaseIntegrinsIntercellular Adhesion Molecule-1MiceNF-kappa BPhosphorylationProtein TransportRac GTP-Binding ProteinsReactive Oxygen SpeciesSignal TransductionStress, MechanicalTranscription Factor RelATumor Necrosis Factor-alphaConceptsFocal adhesion kinaseAdhesion kinaseNF-kappaBRac activationTranscriptional activityDependent genesEndothelial cellsIntegrin activationP65 NF-kappaB subunitDegradation of IkappaBReactive oxygen productionFluid shear stressNF-kappaB subunitsSerine 536Phosphorylation of p65Novel mechanismNF-kappaB activationKinaseNF-kappaB phosphorylationPhosphorylationActivationNF-κBOxygen productionHydrogen peroxideCellsSrc phosphorylation of RhoGDI2 regulates its metastasis suppressor function
Wu Y, Moissoglu K, Wang H, Wang X, Frierson HF, Schwartz MA, Theodorescu D. Src phosphorylation of RhoGDI2 regulates its metastasis suppressor function. Proceedings Of The National Academy Of Sciences Of The United States Of America 2009, 106: 5807-5812. PMID: 19321744, PMCID: PMC2667073, DOI: 10.1073/pnas.0810094106.Peer-Reviewed Original ResearchMeSH KeywordsCell Line, TumorDisease ProgressionGene Expression ProfilingGuanine Nucleotide Dissociation InhibitorsHumansImmunohistochemistryNeoplasm MetastasisPhosphorylationProtein BindingRho Guanine Nucleotide Dissociation Inhibitor betaRho-Specific Guanine Nucleotide Dissociation InhibitorsSrc-Family KinasesTumor Suppressor ProteinsUrinary Bladder NeoplasmsConceptsMetastasis suppressionSrc levelsSrc phosphorylation siteProtein interaction analysisMetastasis suppressor functionRhoGDI2 expressionSuppressor of metastasisGene expression profilingRhoGDI2 functionTyr-153Kinase bindsPhosphorylation sitesAmount of Rac1Expression profilingInteraction partnersSrc phosphorylationSrc inhibitorStable expressionBladder cancerSuppressor functionRhoGDI2Cancer cell linesCell membraneSrcPhosphorylation
2007
Induction of Vascular Permeability: βPIX and GIT1 Scaffold the Activation of Extracellular Signal-regulated Kinase by PAK
Stockton R, Reutershan J, Scott D, Sanders J, Ley K, Schwartz MA. Induction of Vascular Permeability: βPIX and GIT1 Scaffold the Activation of Extracellular Signal-regulated Kinase by PAK. Molecular Biology Of The Cell 2007, 18: 2346-2355. PMID: 17429073, PMCID: PMC1877103, DOI: 10.1091/mbc.e06-07-0584.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAnimalsCapillary PermeabilityCattleCell Cycle ProteinsCells, CulturedEndothelial CellsEnzyme ActivationExtracellular Signal-Regulated MAP KinasesGuanine Nucleotide Exchange FactorsHumansInflammationLipopolysaccharidesLungMiceP21-Activated KinasesPeptidesProtein Serine-Threonine KinasesRho Guanine Nucleotide Exchange FactorsConceptsP21-activated kinaseMitogen-activated protein kinase kinaseEndothelial cell-cell junctionsExtracellular signal-regulated kinaseCell-cell junctionsProtein kinase kinaseMyosin light chain phosphorylationLight chain phosphorylationSignal-regulated kinaseCell-permeant peptideActivation of ERKKinase kinaseExtracellular signalsPAK functionChain phosphorylationCritical regulatorKinaseCell contractilityCell typesCultured endothelial cellsPhosphorylationMouse lung injury modelMyosin phosphorylationEndothelial cellsGIT1Matrix‐specific PAK activation regulates vascular permeability in atherosclerosis
Orr A, Stockton R, Simmers M, Sanders J, Blackman B, Schwartz M. Matrix‐specific PAK activation regulates vascular permeability in atherosclerosis. The FASEB Journal 2007, 21: a268-a268. DOI: 10.1096/fasebj.21.5.a268-d.Peer-Reviewed Original ResearchPAK activationAtherosclerosis-prone regionsCell-cell junctionsActivation of PAKMembrane proteinsPAK phosphorylationBasement membrane proteinsPro-atherosclerotic cytokinesEndothelial permeabilityPAKActivationFibronectinSubendothelial monocytesVivoKinasePhosphorylationProteinP21Vascular permeabilityRecruitmentMatrix-specific p21-activated kinase activation regulates vascular permeability in atherogenesis
Orr AW, Stockton R, Simmers MB, Sanders JM, Sarembock IJ, Blackman BR, Schwartz MA. Matrix-specific p21-activated kinase activation regulates vascular permeability in atherogenesis. Journal Of Cell Biology 2007, 176: 719-727. PMID: 17312022, PMCID: PMC2064028, DOI: 10.1083/jcb.200609008.Peer-Reviewed Original ResearchConceptsP21-activated kinaseP21-activated kinase activationAtherosclerosis-prone regionsCell-cell junctionsBasement membrane proteinsMembrane proteinsPAK phosphorylationActivation of PAKKinase activationPAK activationEndothelial permeabilityFibronectinActivationSubendothelial monocytesVivoKinasePhosphorylationProteinVascular permeabilityAtherogenesisRecruitmentCells
2006
Integrin-mediated adhesion regulates membrane order
Gaus K, Le Lay S, Balasubramanian N, Schwartz MA. Integrin-mediated adhesion regulates membrane order. Journal Of Cell Biology 2006, 174: 725-734. PMID: 16943184, PMCID: PMC2064315, DOI: 10.1083/jcb.200603034.Peer-Reviewed Original ResearchConceptsFocal adhesionsMembrane orderCholesterol-dependent domainsSpecific protein complexesLipid raft propertiesIntegrin-mediated adhesionFluorescent probe LaurdanProtein complexesRaft componentsDetachment of cellsRaft propertiesCell adhesionCell membraneSubunit BProbe LaurdanCaveolinCaveolaeAdhesionDomainImportant consequencesTyr14Caveolin1PhosphorylationTraffickingTwo-photon microscopy
2005
Phospho-caveolin-1 mediates integrin-regulated membrane domain internalization
del Pozo MA, Balasubramanian N, Alderson NB, Kiosses WB, Grande-García A, Anderson RG, Schwartz MA. Phospho-caveolin-1 mediates integrin-regulated membrane domain internalization. Nature Cell Biology 2005, 7: 901-908. PMID: 16113676, PMCID: PMC1351395, DOI: 10.1038/ncb1293.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCaveolaeCaveolin 1CaveolinsCell AdhesionCell ProliferationDynamin IIEndocytosisExtracellular MatrixExtracellular Signal-Regulated MAP KinasesFocal AdhesionsIntegrinsMembrane MicrodomainsMiceMice, KnockoutMicroscopy, Electron, TransmissionNeoplasm InvasivenessNeoplasmsNIH 3T3 CellsPhosphatidylinositol 3-KinasesPhosphorylationRac GTP-Binding ProteinsConceptsCaveolin-1Cholesterol-enriched membrane microdomainsPhosphatidylinositol-3-OH kinaseCell detachmentNovel molecular mechanismCholesterol-rich domainsInhibition of ERKMembrane microdomainsFocal adhesionsDynamin 2Plasma membraneMolecular mechanismsTumor suppressionTyr-14Multiple pathwaysNormal cellsInternalizationERKRacPathwayCaveolaeKinasePhosphorylationAdhesionMicrodomains
2004
p21-activated Kinase Regulates Endothelial Permeability through Modulation of Contractility*
Stockton RA, Schaefer E, Schwartz MA. p21-activated Kinase Regulates Endothelial Permeability through Modulation of Contractility*. Journal Of Biological Chemistry 2004, 279: 46621-46630. PMID: 15333633, DOI: 10.1074/jbc.m408877200.Peer-Reviewed Original ResearchMeSH KeywordsActinsAnimalsBlotting, WesternCattleCell CommunicationCells, CulturedCytokinesCytoskeletonEndothelium, VascularEnzyme ActivationHumansInflammationIschemiaMicroscopy, FluorescenceMuscle ContractionMyosin Light ChainsP21-Activated KinasesPeptidesPhosphorylationProtein Serine-Threonine KinasesProtein TransportThrombinTime FactorsTransfectionUmbilical VeinsConceptsP21-activated kinaseClose cell-cell associationsEndothelial cell-cell junctionsCell-cell junctionsActin stress fibersCell-cell associationsSuitable drug targetsGrowth factorMyosin phosphorylationHuman umbilical vein endothelial cellsCentral regulatorStress fibersUmbilical vein endothelial cellsEndothelial cellsPAK activationDrug targetsVein endothelial cellsCell contractilityMultiple growth factorsParacellular poresEndothelial permeabilityPhosphorylationPathological processesPathological conditionsPotential role
1998
Integrins Regulate the Association and Phosphorylation of Paxillin by c-Abl*
Lewis J, Schwartz M. Integrins Regulate the Association and Phosphorylation of Paxillin by c-Abl*. Journal Of Biological Chemistry 1998, 273: 14225-14230. PMID: 9603926, DOI: 10.1074/jbc.273.23.14225.Peer-Reviewed Original ResearchConceptsC-AblCell adhesionTyrosine kinaseFocal adhesion protein paxillinNon-receptor tyrosine kinasePhosphorylation of paxillinC-Abl kinaseEffects of integrinsFocal adhesionsProtein paxillinIntegrin regulationPaxillinTransient recruitmentKinaseIntegrinsCell functionProteinAdhesionPhosphorylationTyrosineRegulationABLRecruitmentActivationLocalization
1995
Integrin signaling: roles for the cytoplasmic tails of αIIbβ3 in the tyrosine phosphorylation of pp125FAK
Leong L, Hughes P, Schwartz M, Ginsberg M, Shattil S. Integrin signaling: roles for the cytoplasmic tails of αIIbβ3 in the tyrosine phosphorylation of pp125FAK. Journal Of Cell Science 1995, 108: 3817-3825. PMID: 8719888, DOI: 10.1242/jcs.108.12.3817.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsCell Adhesion MoleculesCHO CellsCricetinaeCytoplasmEnzyme ActivationFocal Adhesion Kinase 1Focal Adhesion Protein-Tyrosine KinasesMolecular Sequence DataMutagenesisPhosphorylationPlatelet Glycoprotein GPIIb-IIIa ComplexProtein-Tyrosine KinasesSignal TransductionConceptsAlpha IIbCytoplasmic tailTruncation mutantsFAK phosphorylationCytoplasmic tail truncation mutantsMembrane-proximal portionProtein tyrosine kinasesMembrane-distal portionExtent of phosphorylationLatter mutantTyrosine phosphorylationPersistent phosphorylationCell spreadingMutantsTyrosine kinaseCellular responsesExtracellular portionPhosphorylationCell adhesionFAKAdhesive ligandsCHO cellsPp125FAKAdditional mutationsBeta 3
1993
A 50-kDa integrin-associated protein is required for integrin-regulated calcium entry in endothelial cells.
Schwartz M, Brown E, Fazeli B. A 50-kDa integrin-associated protein is required for integrin-regulated calcium entry in endothelial cells. Journal Of Biological Chemistry 1993, 268: 19931-19934. PMID: 8376355, DOI: 10.1016/s0021-9258(20)80675-9.Peer-Reviewed Original ResearchConceptsIntegrin-associated proteinExtracellular matrix proteinsMatrix proteinsEndothelial cellsIAP functionTransmembrane domainTyrosine phosphorylationPrimary sequenceEndothelial cell adhesionCell adhesionMembrane channelsProteinAnti-integrin antibodiesCalcium entryCellsIntracellular pHIon transportInflux of Ca2Activation of neutrophilsActivationCalcium channelsCalcium influxPhosphorylationNeutrophil functionMonoclonal antibodies
1992
Transmembrane signalling by integrins
Schwartz M. Transmembrane signalling by integrins. Trends In Cell Biology 1992, 2: 304-308. PMID: 14731926, DOI: 10.1016/0962-8924(92)90120-c.Peer-Reviewed Original Research