2013
N-cadherin regulates spatially polarized signals through distinct p120ctn and β-catenin-dependent signalling pathways
Ouyang M, Lu S, Kim T, Chen CE, Seong J, Leckband DE, Wang F, Reynolds AB, Schwartz MA, Wang Y. N-cadherin regulates spatially polarized signals through distinct p120ctn and β-catenin-dependent signalling pathways. Nature Communications 2013, 4: 1589. PMID: 23481397, PMCID: PMC3602931, DOI: 10.1038/ncomms2560.Peer-Reviewed Original ResearchMeSH KeywordsActin CytoskeletonAnimalsBeta CateninCadherinsCateninsCell PolarityChickensCHO CellsCricetinaeDelta CateninEmbryo, MammalianFibroblastsFluorescent DyesIntegrinsIntercellular JunctionsMiceModels, BiologicalPhosphatidylinositol 3-KinasesProtein BindingRac GTP-Binding ProteinsRatsRecombinant Fusion ProteinsRNA, Small InterferingSignal TransductionConceptsMyosin II light chainRac activityActin filamentsSmall GTPase RacΒ-catenin-dependent signaling pathwaysHigher phosphoinositidesCellular functionsGTPase RacDistinct effectorsMolecular signalsSignaling pathwaysMolecular activityLight chainNeighbouring cellsN-cadherinPhosphoinositideIntercellular junctionsIntegrin α5RacCellsComplexesFilamentsP120ctnSpatial distributionEffectors
2011
Effects of integrin-mediated cell adhesion on plasma membrane lipid raft components and signaling
Norambuena A, Schwartz MA. Effects of integrin-mediated cell adhesion on plasma membrane lipid raft components and signaling. Molecular Biology Of The Cell 2011, 22: 3456-3464. PMID: 21795400, PMCID: PMC3172269, DOI: 10.1091/mbc.e11-04-0361.Peer-Reviewed Original ResearchConceptsLipid raft componentsRaft componentsLipid raftsCyclic adenosine monophosphateCell detachmentCell adhesionLipid raft markersGlycosylphosphatidylinositol-linked proteinsRaft associationRaft markersRho GTPasesNonraft fractionsDetachment of cellsElevation of cAMPStudy of integrinsTermination of growthPlasma membraneH-RasAnchorage dependenceKey defenseCell growthFlotillin2Sucrose gradientsCancer metastasisLipid tails
2010
Myosin II directly binds and inhibits Dbl family guanine nucleotide exchange factors: a possible link to Rho family GTPases
Lee CS, Choi CK, Shin EY, Schwartz MA, Kim EG. Myosin II directly binds and inhibits Dbl family guanine nucleotide exchange factors: a possible link to Rho family GTPases. Journal Of Cell Biology 2010, 190: 663-674. PMID: 20713598, PMCID: PMC2928003, DOI: 10.1083/jcb.201003057.Peer-Reviewed Original ResearchMeSH KeywordsActomyosinAnimalsBinding SitesCdc42 GTP-Binding ProteinCell AdhesionCell MovementEnzyme ActivationGuanine Nucleotide Exchange FactorsHumansJurkat CellsMiceMyosin Type IINIH 3T3 CellsPlatelet-Derived Growth FactorProtein BindingRac1 GTP-Binding ProteinRatsRecombinant Fusion ProteinsRho GTP-Binding ProteinsRho Guanine Nucleotide Exchange FactorsRNA, Small InterferingConceptsFocal complex formationDbl family guanineMyosin IIExchange factorFamily guanineATPase activityNonmuscle myosin IIComplex formationGEF activitySpatiotemporal regulationRho familyCdc42 GTPasesAdhesion dynamicsRho GTPasesCdc42 activationLamellipodial protrusionCell protrusionsActomyosin contractionGEFNIH3T3 fibroblastsFunctional linkCell migrationGTPasesCatalytic siteHomology modules
2006
In Vivo Dynamics of Rac-Membrane Interactions
Moissoglu K, Slepchenko BM, Meller N, Horwitz AF, Schwartz MA. In Vivo Dynamics of Rac-Membrane Interactions. Molecular Biology Of The Cell 2006, 17: 2770-2779. PMID: 16597700, PMCID: PMC1474787, DOI: 10.1091/mbc.e06-01-0005.Peer-Reviewed Original ResearchMeSH Keywords3T3 CellsAnimalsCell MembraneComputer SimulationDiffusionGenes, ReporterGuanine Nucleotide Dissociation InhibitorsKineticsMiceMicroscopy, ConfocalModels, TheoreticalPlasmidsProtein TransportRac GTP-Binding ProteinsRecombinant Fusion ProteinsRecombinant ProteinsRho-Specific Guanine Nucleotide Dissociation InhibitorsConceptsGuanine Nucleotide Dissociation InhibitorGTPase-activating proteinsGTP-RacNucleotide exchange factorsVivo dynamicsSmall hairpin RNADissociation inhibitorMembrane associationExchange factorRac functionGEF Tiam1Hairpin RNARhoGDIPhotobleaching methodRacCytosolOverexpressionMajor routeDissociation rate constantsTiam1RNAProteinDetectable rateMembraneActivation
2004
Integrins 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
Modulation of Rac Localization and Function by Dynamin
Schlunck G, Damke H, Kiosses WB, Rusk N, Symons MH, Waterman-Storer CM, Schmid SL, Schwartz MA. Modulation of Rac Localization and Function by Dynamin. Molecular Biology Of The Cell 2003, 15: 256-267. PMID: 14617821, PMCID: PMC307545, DOI: 10.1091/mbc.e03-01-0019.Peer-Reviewed Original ResearchConceptsLamellipodia formationDorsal rufflesRac activityCell spreadingFluorescence resonance energy transfer (FRET) imagingFormation of lamellipodiaFormation of phagosomesGTPase dynaminFocal complexesSmall GTPasesRho familyEndocytic pathwayDynaminCell adhesionCell migrationRufflesRacLamellipodiaPredominant localizationIndispensable roleLocalizationK44AGTPasesMacropinosomesInvadopodiaLocalized Cdc42 Activation, Detected Using a Novel Assay, Mediates Microtubule Organizing Center Positioning in Endothelial Cells in Response to Fluid Shear Stress*
Tzima E, Kiosses WB, del Pozo MA, Schwartz MA. Localized Cdc42 Activation, Detected Using a Novel Assay, Mediates Microtubule Organizing Center Positioning in Endothelial Cells in Response to Fluid Shear Stress*. Journal Of Biological Chemistry 2003, 278: 31020-31023. PMID: 12754216, DOI: 10.1074/jbc.m301179200.Peer-Reviewed Original ResearchConceptsMicrotubule organizing centerCdc42 activityCdc42 activationFluid shear stressSmall GTPase Cdc42Protein kinase CzetaGTPase Cdc42Early embryosEndothelial cellsIntegrin dynamicsOrganizing centerCdc42Extracellular matrixLocalized activationFluorescence energy transferMTOC localizationVascular endothelial cellsSingle cellsNovel assayCellsActivationPar6CzetaGolgiEmbryos
2002
A Dominant-Negative p65 PAK Peptide Inhibits Angiogenesis
Kiosses WB, Hood J, Yang S, Gerritsen ME, Cheresh DA, Alderson N, Schwartz MA. A Dominant-Negative p65 PAK Peptide Inhibits Angiogenesis. Circulation Research 2002, 90: 697-702. PMID: 11934838, DOI: 10.1161/01.res.0000014227.76102.5d.Peer-Reviewed Original ResearchIntegrins regulate GTP-Rac localized effector interactions through dissociation of Rho-GDI
Del Pozo MA, Kiosses WB, Alderson NB, Meller N, Hahn KM, Schwartz MA. Integrins regulate GTP-Rac localized effector interactions through dissociation of Rho-GDI. Nature Cell Biology 2002, 4: 232-239. PMID: 11862216, DOI: 10.1038/ncb759.Peer-Reviewed Original Research
2001
Increased filamin binding to β-integrin cytoplasmic domains inhibits cell migration
Calderwood D, Huttenlocher A, Kiosses W, Rose D, Woodside D, Schwartz M, Ginsberg M. Increased filamin binding to β-integrin cytoplasmic domains inhibits cell migration. Nature Cell Biology 2001, 3: 1060-1068. PMID: 11781567, DOI: 10.1038/ncb1201-1060.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SubstitutionAnimalsBinding SitesCell MovementCell PolarityCHO CellsContractile ProteinsCricetinaeCytoplasmCytoskeletonFibronectinsFilaminsFocal AdhesionsHumansIntegrin beta ChainsIntegrinsIsoleucineJurkat CellsMicrofilament ProteinsProtein Structure, TertiaryRecombinant Fusion ProteinsTalinValineConceptsFocal adhesion formationFilamin bindingCell migrationMembrane protrusionsMatrix assemblyIntegrin-dependent cell migrationFibronectin matrix assemblyAmino acid substitutionsInhibits cell migrationAnimal developmentActin cytoskeletonIntegrin tailsBiochemical signalsAdhesion receptorsFilaminCell polarizationTalinAcid substitutionsExtracellular matrixAdhesion formationTailBindingAssemblyMigrationSelective lossc-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
Localized Rac Activation Dynamics Visualized in Living Cells
Kraynov V, Chamberlain C, Bokoch G, Schwartz M, Slabaugh S, Hahn K. Localized Rac Activation Dynamics Visualized in Living Cells. Science 2000, 290: 333-337. PMID: 11030651, DOI: 10.1126/science.290.5490.333.Peer-Reviewed Original ResearchConceptsSmall guanosine triphosphatasesSpatio-temporal controlMembrane rufflesGuanosine triphosphatasesSubcellular localizationNucleotide stateRac activationProtein activityDownstream targetsMotile cellsLiving cellsSpatial controlSpatio-temporal dynamicsGradient of activationCellsActivation dynamicsActivationRufflesTriphosphatasesPrecise spatial controlProteinRacLeading edgeApplicable approachLocalized effectDeath Effector Domain Protein PEA-15 Potentiates Ras Activation of Extracellular Signal Receptor-activated Kinase by an Adhesion-independent Mechanism
Ramos J, Hughes P, Renshaw M, Schwartz M, Formstecher E, Chneiweiss H, Ginsberg M. Death Effector Domain Protein PEA-15 Potentiates Ras Activation of Extracellular Signal Receptor-activated Kinase by an Adhesion-independent Mechanism. Molecular Biology Of The Cell 2000, 11: 2863-2872. PMID: 10982386, PMCID: PMC14961, DOI: 10.1091/mbc.11.9.2863.Peer-Reviewed Original ResearchMeSH Keywords3T3 CellsAnimalsApoptosis Regulatory ProteinsCell AdhesionCell LineCHO CellsCricetinaeEnzyme ActivationGuanosine TriphosphateHumansIntracellular Signaling Peptides and ProteinsJNK Mitogen-Activated Protein KinasesMAP Kinase Kinase Kinase 1MiceMitogen-Activated Protein KinasesP38 Mitogen-Activated Protein KinasesPhosphoproteinsProtein Serine-Threonine KinasesRas ProteinsRecombinant Fusion ProteinsSignal TransductionConceptsPEA-15 expressionPEA-15ERK activationMitogen-activated protein kinase kinaseMitogen-activated protein kinase pathwayAdhesion-independent mechanismsRas-dependent mannerProtein kinase kinaseRegulation of apoptosisProtein kinase pathwayChinese hamster ovary cellsRas guanosineKinase kinaseRas activationSignal receptorHamster ovary cellsH-RasKinase pathwayERK activityIntegrin activationERK signalingAnchorage dependenceOncogenic processesOvary cellsApoptosisAdhesion 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 cellsRacPAKMembraneCellsAdhesionActivationDetermination of GTP loading on Rho
Ren X, Schwartz M. Determination of GTP loading on Rho. Methods In Enzymology 2000, 325: 264-272. PMID: 11036609, DOI: 10.1016/s0076-6879(00)25448-7.Peer-Reviewed Original ResearchConceptsRho-binding domainGTP-RhoLow molecular weight GTPaseAffinity precipitation assaysActin cytoskeleton organizationGTP loadingCytoskeleton organizationWeight GTPaseGTPase activityRho effectorCell lysatesGTPaseRhoPrecipitation assaysTRBDWestern immunoblottingDomainQuality controlPositive controlAssaysRhotekinEffectorsProtein
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 TransductionTransfectionMutational Analysis of Cell Cycle Inhibition by Integrin β1C *
Meredith J, Kiosses W, Takada Y, Schwartz M. Mutational Analysis of Cell Cycle Inhibition by Integrin β1C *. Journal Of Biological Chemistry 1999, 274: 8111-8116. PMID: 10075712, DOI: 10.1074/jbc.274.12.8111.Peer-Reviewed Original ResearchMeSH KeywordsAlternative SplicingAmino Acid SequenceAnimalsCells, CulturedDNA Mutational AnalysisDNA ReplicationDose-Response Relationship, DrugHumansIntegrin beta1MiceMice, Inbred C3HMolecular Sequence DataMutagenesis, Site-DirectedReceptors, Interleukin-2Recombinant Fusion ProteinsStructure-Activity RelationshipConceptsCytoplasmic domainGreen fluorescent protein fusion proteinFluorescent protein fusion proteinProtein fusion proteinMembrane-proximal regionCell cycle progressionAnalysis of deletionsHuman interleukin-2 receptorBeta5 cytoplasmic domainsMembrane targetingMouse 10T1/2 cellsGrowth inhibitionCell cycle inhibitionTransmembrane domainLow expression levelsProstate epithelial cellsAcid domainCytoplasmic variantsTac subunitMutational analysisCycle progressionFusion proteinIntact receptorCell line DU145Human endothelial cell line
1997
Affinity Modulation of Platelet Integrin αIIbβ3 by β3-Endonexin, a Selective Binding Partner of the β3 Integrin Cytoplasmic Tail
Kashiwagi H, Schwartz M, Eigenthaler M, Davis K, Ginsberg M, Shattil S. Affinity Modulation of Platelet Integrin αIIbβ3 by β3-Endonexin, a Selective Binding Partner of the β3 Integrin Cytoplasmic Tail. Journal Of Cell Biology 1997, 137: 1433-1443. PMID: 9182673, PMCID: PMC2132534, DOI: 10.1083/jcb.137.6.1433.Peer-Reviewed Original ResearchConceptsGreen fluorescent proteinIntegrin cytoplasmic tailsCytoplasmic tailSuch protein-protein interactionsSelective binding partnerΒ3 integrin cytoplasmic tailProtein-protein interactionsAffinity modulationFibrinogen-dependent aggregationPlatelet integrin αIIbβ3Β3-endonexinBinding partnerEnergy-dependent fashionAcid proteinH-RasIntegrin alphaIIbbeta3Adhesive functionMetabolic regulationFluorescent proteinBeta3 tailIntegrin αIIbβ3Cell lysatesCHO cellsAffinity stateSurface expression