2015
Rac1 functions as a reversible tension modulator to stabilize VE-cadherin trans-interaction
Daneshjou N, Sieracki N, van Nieuw Amerongen GP, Conway D, Schwartz M, Komarova Y, Malik A. Rac1 functions as a reversible tension modulator to stabilize VE-cadherin trans-interaction. Journal Of Cell Biology 2015, 208: 23-32. PMID: 25559184, PMCID: PMC4284224, DOI: 10.1083/jcb.201409108.Peer-Reviewed Original ResearchActomyosinAdherens JunctionsAntigens, CDCadherinsCell AdhesionCells, CulturedEndothelial CellsEnzyme ActivationHumansKineticsMicroscopy, FluorescenceMicroscopy, VideoModels, BiologicalMyosin Type IIProtein BindingProtein Kinase InhibitorsProtein MultimerizationProtein StabilityRac1 GTP-Binding ProteinRho-Associated KinasesTime-Lapse ImagingTransfection
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 cellsMatrix-Specific Protein Kinase A Signaling Regulates p21-Activated Kinase Activation by Flow in Endothelial Cells
Funk SD, Yurdagul A, Green JM, Jhaveri KA, Schwartz MA, Orr AW. Matrix-Specific Protein Kinase A Signaling Regulates p21-Activated Kinase Activation by Flow in Endothelial Cells. Circulation Research 2010, 106: 1394-1403. PMID: 20224042, PMCID: PMC2862370, DOI: 10.1161/circresaha.109.210286.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnti-Inflammatory AgentsBasement MembraneCattleCdc42 GTP-Binding ProteinCells, CulturedCyclic AMP-Dependent Protein KinasesEndothelial CellsEnzyme ActivationEnzyme ActivatorsHumansIloprostInflammationInflammation MediatorsInjections, IntraperitonealIntegrinsMaleMechanotransduction, CellularMiceMice, Inbred C57BLNF-kappa BP21-Activated KinasesPhosphorylationProtein Kinase InhibitorsPulsatile FlowRac GTP-Binding ProteinsRegional Blood FlowStress, MechanicalTime FactorsTransfectionConceptsInflammatory gene expressionNF-kappaB activationInflammatory signalingEndothelial cellsProstacyclin analogue iloprostBasement membrane proteinsBlood flow patternsPKA-dependent inhibitionInflammatory pathwaysAnalogue iloprostGene expressionKappaB activationNF-kappaB.Subendothelial extracellular matrixNuclear factorPAK activationBasement membrane
2008
Endogenous RhoG is dispensable for integrin-mediated cell spreading but contributes to Rac-independent migration
Meller J, Vidali L, Schwartz MA. Endogenous RhoG is dispensable for integrin-mediated cell spreading but contributes to Rac-independent migration. Journal Of Cell Science 2008, 121: 1981-1989. PMID: 18505794, PMCID: PMC2759683, DOI: 10.1242/jcs.025130.Peer-Reviewed Original Research
2007
Function of the N-terminus of zizimin1: autoinhibition and membrane targeting
Meller N, Westbrook MJ, Shannon JD, Guda C, Schwartz MA. Function of the N-terminus of zizimin1: autoinhibition and membrane targeting. Biochemical Journal 2007, 409: 525-533. PMID: 17935486, PMCID: PMC2740492, DOI: 10.1042/bj20071263.Peer-Reviewed Original ResearchConceptsGEF domainCZH proteinsRho family small GTPasesPH domain bindsCdc42-specific GEFMultiple cellular functionsBasis of homologyN-terminal regionSmall GTPasesDomain bindsGEF activityRho proteinsCellular functionsRho-GEFsNovel functionN-terminusCritical regulatorStructural domainsLimited proteolysisZizimin1ProteinBindsDomainMembraneGTPases
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
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 roleIntegrins Regulate Rac Targeting by Internalization of Membrane Domains
del Pozo MA, Alderson NB, Kiosses WB, Chiang HH, Anderson RG, Schwartz MA. Integrins Regulate Rac Targeting by Internalization of Membrane Domains. Science 2004, 303: 839-842. PMID: 14764880, DOI: 10.1126/science.1092571.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBinding SitesCell AdhesionCell LineCell MembraneCells, CulturedCholera ToxinCholesterolG(M1) GangliosideGlycosylphosphatidylinositolsGuanosine TriphosphateHumansIntegrin beta1IntegrinsLiposomesMembrane MicrodomainsMiceNIH 3T3 CellsRac1 GTP-Binding ProteinRatsRecombinant Fusion ProteinsSignal TransductionTransfectionConceptsMembrane domainsLipid raftsLipid raft markersPlasma membrane cholesterolCholesterol-rich membranesCell plasma membraneMembrane targetingAdhesion of cellsSmall GTPRaft markersIntegrin signalsPlasma membraneDownstream effectorsEffector activationMembrane lipidsMembrane cholesterolAnchorage-dependent cellsExtracellular matrixCell detachmentNonadherent cellsInternalizationRaftsCellsTargetingMembrane
2003
Rho-ROCK-LIMK-Cofilin Pathway Regulates Shear Stress Activation of Sterol Regulatory Element Binding Proteins
Lin T, Zeng L, Liu Y, DeFea K, Schwartz MA, Chien S, Shyy J. Rho-ROCK-LIMK-Cofilin Pathway Regulates Shear Stress Activation of Sterol Regulatory Element Binding Proteins. Circulation Research 2003, 92: 1296-1304. PMID: 12775580, DOI: 10.1161/01.res.0000078780.65824.8b.Peer-Reviewed Original ResearchMeSH KeywordsActin Depolymerizing FactorsActinsAnimalsCattleCCAAT-Enhancer-Binding ProteinsCell AdhesionCells, CulturedCHO CellsCricetinaeDNA-Binding ProteinsEndothelium, VascularHumansIntracellular Signaling Peptides and ProteinsLim KinasesLuciferasesMembrane ProteinsMicrofilament ProteinsMicroscopy, FluorescenceMutationPlasmidsProtein KinasesProtein Serine-Threonine KinasesProtein TransportProteinsRho GTP-Binding ProteinsRho-Associated KinasesSignal TransductionSterol Regulatory Element Binding Protein 1Sterol Regulatory Element Binding Protein 2Stress, MechanicalTranscription FactorsTransfectionConceptsSterol regulatory element-binding proteinLIMK-cofilin pathwayRegulatory element-binding proteinLIM kinaseElement-binding proteinRho-ROCKBinding proteinFluid shear stressSREBP cleavage-activating proteinSignal transduction pathwaysSmall GTPase RhoStress activationShear stress activationGolgi transportS2P proteasesTransduction pathwaysNegative mutantGTPase RhoSREBP activationIntegrin activationEndoplasmic reticulumEndothelial cell functionVascular endothelial cellsCaspase-3Protein
2002
Activation of Rac1 by shear stress in endothelial cells mediates both cytoskeletal reorganization and effects on gene expression
Tzima E, Del Pozo MA, Kiosses WB, Mohamed SA, Li S, Chien S, Schwartz MA. Activation of Rac1 by shear stress in endothelial cells mediates both cytoskeletal reorganization and effects on gene expression. The EMBO Journal 2002, 21: 6791-6800. PMID: 12486000, PMCID: PMC139108, DOI: 10.1093/emboj/cdf688.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCattleCell AdhesionCells, CulturedCytoskeletonDimerizationEnergy TransferEnzyme ActivationGene Expression RegulationGenes, DominantGreen Fluorescent ProteinsGTP PhosphohydrolasesIntercellular Adhesion Molecule-1LeukocytesLuciferasesLuminescent ProteinsMicroscopy, FluorescenceNF-kappa BPlasmidsProtein TransportRac GTP-Binding ProteinsRac1 GTP-Binding ProteinSpectrometry, FluorescenceStress, MechanicalTime FactorsTransfectionConceptsGene expressionFluorescence resonance energy transferSmall GTPase RacActivation of Rac1Endothelial cellsFocal adhesionsCytoskeletal organizationCytoskeletal reorganizationGTPase RacRac1 activationAdhesion receptorsResonance energy transferExtracellular matrixNuclear factor-kappaBNew integrinRac1Hemodynamic shear stressSubsequent expressionFactor-kappaBCell alignmentExpressionUnifying modelHemodynamic forcesCell adhesion molecule-1CellsEffects of cell tension on the small GTPase Rac
Katsumi A, Milanini J, Kiosses WB, del Pozo MA, Kaunas R, Chien S, Hahn KM, Schwartz MA. Effects of cell tension on the small GTPase Rac. Journal Of Cell Biology 2002, 158: 153-164. PMID: 12105187, PMCID: PMC2173027, DOI: 10.1083/jcb.200201105.Peer-Reviewed Original ResearchMeSH KeywordsAmidesAnimalsAzepinesCell LineCell MembraneCell MovementCollagenDose-Response Relationship, DrugEnergy TransferGTP PhosphohydrolasesGuanine Nucleotide Exchange FactorsMicroscopy, FluorescenceMicroscopy, Phase-ContrastMicroscopy, VideoNaphthalenesNeoplasm ProteinsProteinsPseudopodiaPyridinesRac GTP-Binding ProteinsRatsStress, MechanicalTime FactorsT-Lymphoma Invasion and Metastasis-inducing Protein 1Transfection
2001
Activation of integrins in endothelial cells by fluid shear stress mediates Rho‐dependent cytoskeletal alignment
Tzima E, del Pozo M, Shattil S, Chien S, Schwartz M. Activation of integrins in endothelial cells by fluid shear stress mediates Rho‐dependent cytoskeletal alignment. The EMBO Journal 2001, 20: 4639-4647. PMID: 11532928, PMCID: PMC125600, DOI: 10.1093/emboj/20.17.4639.Peer-Reviewed Original ResearchAnimalsAortaCattleCells, CulturedCulture Media, Serum-FreeCytoskeletonEndothelium, VascularExtracellular Matrix ProteinsFibronectinsGreen Fluorescent ProteinsIntegrinsKineticsLuminescent ProteinsProtein ConformationReceptors, VitronectinRecombinant ProteinsRho GTP-Binding ProteinsStress, MechanicalTime FactorsTransfectionc-Abl Tyrosine Kinase Binds and Phosphorylates Phospholipid Scramblase 1*
Sun J, Zhao J, Schwartz M, Wang J, Wiedmer T, Sims P. c-Abl Tyrosine Kinase Binds and Phosphorylates Phospholipid Scramblase 1*. Journal Of Biological Chemistry 2001, 276: 28984-28990. PMID: 11390389, DOI: 10.1074/jbc.m102505200.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAmino Acid SubstitutionAnimalsBinding SitesCarrier ProteinsCell LineCells, CulturedFibroblastsGenes, ablGlutathione TransferaseHumansMembrane ProteinsMiceMice, KnockoutMutagenesis, Site-DirectedPhospholipid Transfer ProteinsPhospholipidsPhosphorylationProtein BindingProto-Oncogene Proteins c-ablRecombinant Fusion ProteinsRepetitive Sequences, Amino AcidSrc Homology DomainsTransfectionTyrosineConceptsPhospholipid scramblase 1SH3 domainC-AblAbl SH3 domainTyr phosphorylationMultiple proline-rich motifsScramblase 1Plasma membrane proteinsC-Abl bindsProline-rich motifDomain-binding siteProline-rich segmentDNA-damaging agent cisplatinC-Abl kinasePlasma membrane phospholipidsTandem repeat sequencesMutation of TyrCell linesCisplatin-induced phosphorylationKinase bindsGenotoxic stressMembrane proteinsDifferent SH3 domainsTransbilayer movementRepeat sequencesRac recruits high-affinity integrin αvβ3 to lamellipodia in endothelial cell migration
Kiosses W, Shattil S, Pampori N, Schwartz M. Rac recruits high-affinity integrin αvβ3 to lamellipodia in endothelial cell migration. Nature Cell Biology 2001, 3: 316-320. PMID: 11231584, DOI: 10.1038/35060120.Peer-Reviewed Original ResearchAndrostadienesAnimalsAntibodies, MonoclonalCattleCell MovementCells, CulturedChromonesCollagenEndothelium, VascularEnzyme InhibitorsGenes, ReporterImmunoglobulin FragmentsMicroinjectionsMicroscopy, FluorescenceMorpholinesPhosphoinositide-3 Kinase InhibitorsProtein BindingPseudopodiaRac GTP-Binding ProteinsReceptors, VitronectinRecombinant Fusion ProteinsTransfectionWortmannin
2000
Stimulation of Fascin Spikes by Thrombospondin-1 Is Mediated by the Gtpases Rac and Cdc42
Adams J, Schwartz M. Stimulation of Fascin Spikes by Thrombospondin-1 Is Mediated by the Gtpases Rac and Cdc42. Journal Of Cell Biology 2000, 150: 807-822. PMID: 10953005, PMCID: PMC2175285, DOI: 10.1083/jcb.150.4.807.Peer-Reviewed Original ResearchMeSH Keywords3T3 CellsActinsAnimalsBridged Bicyclo Compounds, HeterocyclicCarrier ProteinsCdc42 GTP-Binding ProteinCell AdhesionCell LineDepsipeptidesFibronectinsMiceMicrofilament ProteinsMuscle, SkeletalPeptides, CyclicRac GTP-Binding ProteinsRecombinant ProteinsStress, MechanicalThiazolesThiazolidinesThrombospondin 1TransfectionVinculinConceptsActin cytoskeletal organizationCytoskeletal organizationThrombospondin-1Matrix glycoprotein thrombospondin-1Actin-bundling protein fascinRho family GTPasesF-actin turnoverDominant-negative RacLocalization of fascinF-actin microspikesCell migration responseMotility of cellsGlycoprotein thrombospondin-1GTPases RacImportant physiological stimulusActive mutantComponent downstreamProtein fascinCdc42C2C12 myoblastsCell adhesionCell migrationBiochemical assaysExtracellular matrixProlonged activationAdhesion to the extracellular matrix regulates the coupling of the small GTPase Rac to its effector PAK
del Pozo M, Price L, Alderson N, Ren X, Schwartz M. Adhesion to the extracellular matrix regulates the coupling of the small GTPase Rac to its effector PAK. The EMBO Journal 2000, 19: 2008-2014. PMID: 10790367, PMCID: PMC305684, DOI: 10.1093/emboj/19.9.2008.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBiological TransportCdc42 GTP-Binding ProteinCell AdhesionCell LineCell MembraneCulture Media, Serum-FreeCytoplasmEnzyme ActivationExtracellular MatrixFibronectinsGrowth SubstancesGuanosine TriphosphateIntegrinsMiceMutationMyristic AcidP21-Activated KinasesProtein BindingProtein Serine-Threonine KinasesRac GTP-Binding ProteinsRatsRecombinant Fusion ProteinsTransfectionConceptsSmall GTPase RacExtracellular matrixGTPase RacEffector PAKMembrane-targeting sequenceCell cycle progressionAbility of RacSoluble growth factorsAdherent cellsRac mutantGrowth factorCytoskeletal organizationPAK activationOncogenic transformationGene expressionCycle progressionMembrane fractionCell adhesionNon-adherent cellsRacPAKMembraneCellsAdhesionActivation
1999
A Role for P21-Activated Kinase in Endothelial Cell Migration
Kiosses W, Daniels R, Otey C, Bokoch G, Schwartz M. A Role for P21-Activated Kinase in Endothelial Cell Migration. Journal Of Cell Biology 1999, 147: 831-844. PMID: 10562284, PMCID: PMC2156168, DOI: 10.1083/jcb.147.4.831.Peer-Reviewed Original ResearchActininAnimalsCell AdhesionCell LineCell MovementCOS CellsEndothelium, VascularGreen Fluorescent ProteinsLuminescent ProteinsMicrocirculationMicroscopy, VideoModels, BiologicalMyosin Light ChainsP21-Activated KinasesPhosphorylationProtein Serine-Threonine KinasesRecombinant Fusion ProteinsRecombinant ProteinsSrc Homology DomainsTransfectionVinculinFocal Adhesion Kinase Mediates the Integrin Signaling Requirement for Growth Factor Activation of Map Kinase
Renshaw M, Price L, Schwartz M. Focal Adhesion Kinase Mediates the Integrin Signaling Requirement for Growth Factor Activation of Map Kinase. Journal Of Cell Biology 1999, 147: 611-618. PMID: 10545504, PMCID: PMC2151196, DOI: 10.1083/jcb.147.3.611.Peer-Reviewed Original Research3T3 CellsAnimalsCell AdhesionCell Adhesion MoleculesCell DivisionCell Line, TransformedCell Transformation, NeoplasticEnzyme ActivationFibroblastsFocal Adhesion Kinase 1Focal Adhesion Protein-Tyrosine KinasesGene DeletionGenes, DominantGrowth SubstancesIntegrin beta1MiceMitogen-Activated Protein Kinase 1Oncogene Protein pp60(v-src)Protein-Tyrosine KinasesRas ProteinsRecombinant Fusion ProteinsSignal TransductionTransfectionIntegrin-dependent Tyrosine Phosphorylation and Growth Regulation by Vav
Yron I, Deckert M, Reff M, Munshi A, Schwartz M, Altman A. Integrin-dependent Tyrosine Phosphorylation and Growth Regulation by Vav. Cell Communication & Adhesion 1999, 7: 1-11. PMID: 10228731, DOI: 10.3109/15419069909034388.Peer-Reviewed Original ResearchMeSH KeywordsActinsAnimalsCell AdhesionCell Adhesion MoleculesCell DivisionCHO CellsCricetinaeCytoskeletal ProteinsFibronectinsFocal Adhesion Kinase 1Focal Adhesion Protein-Tyrosine KinasesHumansIntegrin beta1Jurkat CellsKineticsOncogene ProteinsPaxillinPhosphoproteinsPhosphorylationPrecipitin TestsProtein-Tyrosine KinasesProto-Oncogene MasProto-Oncogene Proteins c-vavTime FactorsTransfectionTyrosineConceptsRapid phosphorylationIntegrin-dependent tyrosine phosphorylationAdhesion-dependent mannerExchange factor domainB cell antigen receptorAdhesion-dependent increaseIntegrin signal transductionFocal adhesion kinaseExtent of phosphorylationCell surface stimuliCell antigen receptorJurkat T cellsTriton-insoluble fractionVav overexpressionSmall GTPasesBeta 1 integrinRho familyRho GTPasesCytoskeletal organizationSignal transductionAdhesion kinaseTyrosine phosphorylationStress fibersGrowth regulationFactor domain
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