2011
Src and Caveolin-1 Reciprocally Regulate Metastasis via a Common Downstream Signaling Pathway in Bladder Cancer
Thomas S, Overdevest JB, Nitz MD, Williams PD, Owens CR, Sanchez-Carbayo M, Frierson HF, Schwartz MA, Theodorescu D. Src and Caveolin-1 Reciprocally Regulate Metastasis via a Common Downstream Signaling Pathway in Bladder Cancer. Cancer Research 2011, 71: 832-841. PMID: 21148751, PMCID: PMC4306590, DOI: 10.1158/0008-5472.can-10-0730.Peer-Reviewed Original ResearchConceptsActin stress fibersCav-1Active SrcStress fibersPhosphorylation of p190RhoGAPSrc protein levelsDownstream Signaling PathwaysCaveolin-1 expressionActivity of RhoACav-1 overexpressionTail vein inoculationRegulates MetastasisBladder cancerCommon downstreamHuman bladder cancer cellsPhosphorylated formSignaling pathwaysSrc levelsCell migrationBiochemical studiesLung metastasesMetastasis developmentSrc expressionBladder cancer cellsSrc
2010
Cell adhesion: integrating cytoskeletal dynamics and cellular tension
Parsons JT, Horwitz AR, Schwartz MA. Cell adhesion: integrating cytoskeletal dynamics and cellular tension. Nature Reviews Molecular Cell Biology 2010, 11: 633-643. PMID: 20729930, PMCID: PMC2992881, DOI: 10.1038/nrm2957.Peer-Reviewed Original ResearchConceptsRho GTPasesGuanine nucleotide exchange factorsNucleotide exchange factorsGTPase-activating proteinsMyosin II activityActin-myosin contractionCytoskeletal dynamicsActin cytoskeletonCellular tensionExchange factorRho proteinsProtein TyrAdhesion dynamicsMorphogenetic processesCell rearAdhesion sizeCell frontIntegrin clusteringActin polymerizationRho activationMyosin IIDownstream signalingFeedback loopCell migrationComplex feedback loopsMyosin 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
2009
Suppression of RhoG activity is mediated by a syndecan 4–synectin–RhoGDI1 complex and is reversed by PKCα in a Rac1 activation pathway
Elfenbein A, Rhodes JM, Meller J, Schwartz MA, Matsuda M, Simons M. Suppression of RhoG activity is mediated by a syndecan 4–synectin–RhoGDI1 complex and is reversed by PKCα in a Rac1 activation pathway. Journal Of Cell Biology 2009, 186: 75-83. PMID: 19581409, PMCID: PMC2712988, DOI: 10.1083/jcb.200810179.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCarrier ProteinsCluster AnalysisEnzyme ActivationFibroblast Growth Factor 2GTP PhosphohydrolasesGuanine Nucleotide Dissociation InhibitorsHeLa CellsHumansMiceMice, KnockoutModels, BiologicalPhosphorylationPhosphoserineProtein Kinase C-alphaRac1 GTP-Binding ProteinRatsRho GTP-Binding ProteinsRho-Specific Guanine Nucleotide Dissociation InhibitorsSyndecan-4ConceptsFibroblast growth factor-2Polarized activationRac1 activationSmall guanosine triphosphatase Rac1Activation pathwayProtein complexesRac activationPlasma membranePhysiological defectsSyndecan-4RhoGDI1Major regulatorInactive stateGrowth factor 2RhoGRhoG activityProteoglycan receptorsEndothelial migrationTernary complexFactor 2Genetic deletionSynectinRac1PKCalphaActivationRho GDP Dissociation Inhibitor 2 Suppresses Metastasis via Unconventional Regulation of RhoGTPases
Moissoglu K, McRoberts KS, Meier JA, Theodorescu D, Schwartz MA. Rho GDP Dissociation Inhibitor 2 Suppresses Metastasis via Unconventional Regulation of RhoGTPases. Cancer Research 2009, 69: 2838-2844. PMID: 19276387, PMCID: PMC2701105, DOI: 10.1158/0008-5472.can-08-1397.Peer-Reviewed Original ResearchMeSH KeywordsActinsAnimalsCdc42 GTP-Binding ProteinCell AdhesionGuanine Nucleotide Dissociation InhibitorsHumansLung NeoplasmsMiceRac1 GTP-Binding ProteinRho GTP-Binding ProteinsRho Guanine Nucleotide Dissociation Inhibitor betaRhoA GTP-Binding ProteinRho-Specific Guanine Nucleotide Dissociation InhibitorsTumor Suppressor ProteinsUrinary Bladder NeoplasmsVinculinConceptsRho GTPasesFamily of proteinsGDP dissociation inhibitor 2Rho GDP dissociation inhibitor 2Dissociation inhibitor 2Membrane targetingMembrane associationPoint mutantsMetastasis suppressorRac1 activityGTPasesMetastasis suppressionInhibitor 2Suppress metastasisRhoGDI2ProteinSuppression correlatesRhoGDI1Weak inhibitorInhibitionRhoGTPasesMutantsMetastasis inhibitionStrong inhibitionSuppressor
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
2005
Model of coupled transient changes of Rac, Rho, adhesions and stress fibers alignment in endothelial cells responding to shear stress
Civelekoglu-Scholey G, Orr A, Novak I, Meister J, Schwartz M, Mogilner A. Model of coupled transient changes of Rac, Rho, adhesions and stress fibers alignment in endothelial cells responding to shear stress. Journal Of Theoretical Biology 2005, 232: 569-585. PMID: 15588637, DOI: 10.1016/j.jtbi.2004.09.004.Peer-Reviewed Original ResearchRho Proteins in Cell Migration and Metastasis
Titus B, Schwartz M, Theodorescu D. Rho Proteins in Cell Migration and Metastasis. Critical Reviews In Eukaryotic Gene Expression 2005, 15: 103-114. PMID: 16022631, DOI: 10.1615/critreveukaryotgeneexpr.v15.i2.20.Peer-Reviewed Original ResearchMeSH KeywordsAcute-Phase ProteinsAnimalsCell MovementGene ExpressionGenes, Tumor SuppressorMammalsNeoplasm MetastasisRho GTP-Binding ProteinsSignal TransductionRho Proteins in Cell Migration and Metastasis
Titus B, Schwartz MA, Theodorescu D. Rho Proteins in Cell Migration and Metastasis. Critical Reviews In Eukaryotic Gene Expression 2005, 15: 103-114. DOI: 10.1615/critreveukargeneexpr.v15.i2.20.Peer-Reviewed Original ResearchMeSH KeywordsAcute-Phase ProteinsAnimalsCell MovementGene ExpressionGenes, Tumor SuppressorMammalsNeoplasm MetastasisRho GTP-Binding ProteinsSignal Transduction
2004
Rho signalling at a glance
Schwartz M. Rho signalling at a glance. Journal Of Cell Science 2004, 117: 5457-5458. PMID: 15509861, DOI: 10.1242/jcs.01582.Peer-Reviewed Original ResearchAnimalsCdc42 GTP-Binding ProteinFeedback, PhysiologicalHumansIntracellular Signaling Peptides and ProteinsProtein Serine-Threonine KinasesProtein TransportProteinsRac GTP-Binding ProteinsReceptors, Cell SurfaceRho GTP-Binding ProteinsRho-Associated KinasesSignal TransductionWiskott-Aldrich Syndrome Protein
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-3ProteinLocalized 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
Zizimin1, a novel Cdc42 activator, reveals a new GEF domain for Rho proteins
Meller N, Irani-Tehrani M, Kiosses WB, Del Pozo MA, Schwartz MA. Zizimin1, a novel Cdc42 activator, reveals a new GEF domain for Rho proteins. Nature Cell Biology 2002, 4: 639-647. PMID: 12172552, DOI: 10.1038/ncb835.Peer-Reviewed Original ResearchMeSH Keywords3T3 CellsAmino Acid SequenceAnimalsBinding SitesCdc42 GTP-Binding ProteinCloning, MolecularEnzyme ActivationGuanine Nucleotide Exchange FactorsHumansMiceMolecular Sequence DataProtein Structure, TertiaryRho GTP-Binding ProteinsRNA, MessengerSequence Homology, Amino AcidTissue DistributionConceptsGuanine nucleotide exchange factorsCdc42 activatorGEF domainRho family GTPases RacNucleotide exchange factorsCDM proteinsRho proteinsRho familyGTPases RacNew superfamilySequence comparisonCdc42 activationNew proteinsMutational analysisGene expressionBiochemical searchCell migrationProteinDirect interactionCdc42Zizimin1RacActivatorGTPasesDomain
2001
Timing of cyclin D1 expression within G1 phase is controlled by Rho
Welsh C, Roovers K, Villanueva J, Liu Y, Schwartz M, Assoian R. Timing of cyclin D1 expression within G1 phase is controlled by Rho. Nature Cell Biology 2001, 3: 950-957. PMID: 11715015, DOI: 10.1038/ncb1101-950.Peer-Reviewed Original ResearchLigation of Integrin α3β1 by Laminin 5 at the Wound Edge Activates Rho-dependent Adhesion of Leading Keratinocytes on Collagen*
Nguyen B, Ren X, Schwartz M, Carter W. Ligation of Integrin α3β1 by Laminin 5 at the Wound Edge Activates Rho-dependent Adhesion of Leading Keratinocytes on Collagen*. Journal Of Biological Chemistry 2001, 276: 43860-43870. PMID: 11571278, DOI: 10.1074/jbc.m103404200.Peer-Reviewed Original ResearchMeSH KeywordsCell AdhesionCell MovementCells, CulturedCollagenHumansIntegrin alpha3beta1IntegrinsKeratinocytesLamininRho GTP-Binding ProteinsWounds and InjuriesConceptsHuman foreskin keratinocytesLaminin-5Wound edgeCultured human foreskin keratinocytesRho-independent mechanismEndogenous laminin-5Collagen adhesionSpreading of keratinocytesTransition of keratinocytesForeskin keratinocytesDermal collagenKeratinocytesIntegrin α3β1Wound cellsActivation signalsQuiescent keratinocytesCollagenActivation 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 FactorsTransfectionCoordinate signaling by integrins and receptor tyrosine kinases in the regulation of G1 phase cell-cycle progression
Assoian R, Schwartz M. Coordinate signaling by integrins and receptor tyrosine kinases in the regulation of G1 phase cell-cycle progression. Current Opinion In Genetics & Development 2001, 11: 48-53. PMID: 11163150, DOI: 10.1016/s0959-437x(00)00155-6.Peer-Reviewed Original ResearchConceptsCell cycle progressionReceptor tyrosine kinasesG1 phase cyclinsDependent kinasesTyrosine kinasePhase cell cycle progressionG1 phase cell cycle progressionExtracellular matrix proteinsSoluble growth factorsRho GTPasesGrowth factor receptorRegulated signalingMatrix proteinsKinaseG1 phaseCell proliferationIntegrinsCyclinGrowth factorRecent studiesGTPasesActivationReceptorsSignalingERK
2000
Focal adhesion kinase suppresses Rho activity to promote focal adhesion turnover
Ren X, Kiosses W, Sieg D, Otey C, Schlaepfer D, Schwartz M. Focal adhesion kinase suppresses Rho activity to promote focal adhesion turnover. Journal Of Cell Science 2000, 113: 3673-3678. PMID: 11017882, DOI: 10.1242/jcs.113.20.3673.Peer-Reviewed Original ResearchSignaling networks linking integrins and Rho family GTPases
Schwartz M, Shattil S. Signaling networks linking integrins and Rho family GTPases. Trends In Biochemical Sciences 2000, 25: 388-391. PMID: 10916159, DOI: 10.1016/s0968-0004(00)01605-4.Peer-Reviewed Original ResearchAnimalsCell AdhesionExtracellular MatrixIntegrinsPhosphotransferasesRho GTP-Binding ProteinsSignal TransductionDetermination 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