2024
Cellular stiffness sensing through talin 1 in tissue mechanical homeostasis
Chanduri M, Kumar A, Weiss D, Emuna N, Barsukov I, Shi M, Tanaka K, Wang X, Datye A, Kanyo J, Collin F, Lam T, Schwarz U, Bai S, Nottoli T, Goult B, Humphrey J, Schwartz M. Cellular stiffness sensing through talin 1 in tissue mechanical homeostasis. Science Advances 2024, 10: eadi6286. PMID: 39167642, PMCID: PMC11338229, DOI: 10.1126/sciadv.adi6286.Peer-Reviewed Original ResearchConceptsTissue mechanical homeostasisStiffness sensingExtracellular matrixTalin-1Mechanical homeostasisExtracellular matrix mechanicsIncreased cell spreadingCell spreadingTalinMutationsCellular sensingFibrillar collagenReduced axial stiffnessTissue mechanical propertiesMechanical propertiesAxial stiffnessCompliant substratesHomeostasisRupture pressureArp2/3ARPC5LStiffnessHomeostasis hypothesisResident cellsTissue stiffness
2021
Talin in mechanotransduction and mechanomemory at a glance
Goult BT, Brown NH, Schwartz MA. Talin in mechanotransduction and mechanomemory at a glance. Journal Of Cell Science 2021, 134: jcs258749. PMID: 34708856, PMCID: PMC8697387, DOI: 10.1242/jcs.258749.Peer-Reviewed Original ResearchMeSH KeywordsBinding SitesIntegrinsMechanotransduction, CellularProtein BindingSignal TransductionTalinConceptsHelical bundleHead domainC-terminal rod domainIntegrin conformational activationCytoskeletal linker proteinTerminal head domainExtracellular matrix proteinsCryptic binding sitesFlexible neck regionGlance articleAccompanying posterLinker proteinCytoplasmic tailConformational activationRod domainActin filamentsMatrix proteinsCell scienceTalinProteinBinding sitesDomain linksForce inducesDomainMechanotransductionIntegrin-based mechanosensing through conformational deformation
Driscoll TP, Bidone TC, Ahn SJ, Yu A, Groisman A, Voth GA, Schwartz MA. Integrin-based mechanosensing through conformational deformation. Biophysical Journal 2021, 120: 4349-4359. PMID: 34509509, PMCID: PMC8553792, DOI: 10.1016/j.bpj.2021.09.010.Peer-Reviewed Original ResearchMeSH KeywordsCell AdhesionIntegrin alphaVbeta3IntegrinsLigandsMechanical PhenomenaProtein BindingTalinConceptsCellular mechanosensingFocal adhesion kinase activationIntegrin conformational activationLarge-scale conformational transitionsWild-type integrinIntegrin mutantsEmbryonic developmentConformational activationCellular stiffnessHigh-affinity stateKinase activationSubstrate stiffnessBiological processesIntegrin activationCell spreadingMutantsIntegrin conformationTraction stressConformational deformationConformational transitionIntegrinsMechanosensingSoluble ligandsAffinity stateMolecular-level information
2016
Force regulated conformational change of integrin αVβ3
Chen Y, Lee H, Tong H, Schwartz M, Zhu C. Force regulated conformational change of integrin αVβ3. Matrix Biology 2016, 60: 70-85. PMID: 27423389, PMCID: PMC5237428, DOI: 10.1016/j.matbio.2016.07.002.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBiomechanical PhenomenaBiotinylationCell AdhesionCell LineEndothelial CellsErythrocytesExtracellular MatrixFibronectinsGene ExpressionGlassHumansIntegrin alphaVbeta3KineticsLungMiceMolecular ProbesPoint MutationProtein BindingProtein ConformationSignal TransductionSingle Molecule ImagingConceptsConformational changesTransduce signalsSingle-molecule levelIntegrin functionBiomembrane force probeMolecular machinesPhysiological functionsCell adhesionCell surfaceExtracellular matrixPoint mutationsConformational transitionIntegrinsEssential roleTumor metastasisExtended conformationConformationDynamic equilibriumEctodomainMutationsForce probePhagocytosisMembraneAngiogenesisFunction
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
2014
Discovery and characterization of small molecules that target the GTPase Ral
Yan C, Liu D, Li L, Wempe MF, Guin S, Khanna M, Meier J, Hoffman B, Owens C, Wysoczynski CL, Nitz MD, Knabe WE, Ahmed M, Brautigan DL, Paschal BM, Schwartz MA, Jones DN, Ross D, Meroueh SO, Theodorescu D. Discovery and characterization of small molecules that target the GTPase Ral. Nature 2014, 515: 443-447. PMID: 25219851, PMCID: PMC4351747, DOI: 10.1038/nature13713.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsATP-Binding Cassette TransportersCell Line, TumorCell ProliferationComputer SimulationDrug Screening Assays, AntitumorFemaleGTPase-Activating ProteinsHumansMiceModels, MolecularMolecular Targeted TherapyNeoplasmsProtein BindingRal GTP-Binding ProteinsRas ProteinsSignal TransductionSmall Molecule LibrariesSubstrate SpecificityXenograft Model Antitumor AssaysRegulation of Rac1 translocation and activation by membrane domains and their boundaries
Moissoglu K, Kiessling V, Wan C, Hoffman BD, Norambuena A, Tamm LK, Schwartz MA. Regulation of Rac1 translocation and activation by membrane domains and their boundaries. Journal Of Cell Science 2014, 127: 2565-2576. PMID: 24695858, PMCID: PMC4038948, DOI: 10.1242/jcs.149088.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell MembraneFluorescence Resonance Energy TransferGTPase-Activating ProteinsHEK293 CellsHumansMembrane MicrodomainsMiceNIH 3T3 CellsProtein BindingProtein TransportRac1 GTP-Binding ProteinRho-Specific Guanine Nucleotide Dissociation InhibitorsSignal TransductionUnilamellar LiposomesConceptsFluorescence resonance energy transferMembrane domainsRac1 translocationGDP dissociation inhibitor proteinLiquid-ordered membrane domainsGTPase-activating proteinsNon-raft regionsNon-raft domainsBinding of Rac1Activation of Rac1Single-molecule analysisGTP loadingRho GTPasesLipid raftsRac1 localizationRho GTPaseInhibitor proteinResult of inactivationRac1Resonance energy transferFunctional studiesNovel mechanismLipid bilayersTranslocationRafts
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
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
2009
Src 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 membraneSrcPhosphorylationThe Force Is with Us
Schwartz MA. The Force Is with Us. Science 2009, 323: 588-589. PMID: 19179515, DOI: 10.1126/science.1169414.Peer-Reviewed Original Research
2005
Zizimin2: a novel, DOCK180‐related Cdc42 guanine nucleotide exchange factor expressed predominantly in lymphocytes
Nishikimi A, Meller N, Uekawa N, Isobe K, Schwartz MA, Maruyama M. Zizimin2: a novel, DOCK180‐related Cdc42 guanine nucleotide exchange factor expressed predominantly in lymphocytes. FEBS Letters 2005, 579: 1039-1046. PMID: 15710388, DOI: 10.1016/j.febslet.2005.01.006.Peer-Reviewed Original ResearchAmino Acid SequenceAnimalsCdc42 GTP-Binding ProteinCell LineCloning, MolecularEnzyme ActivationGene Expression ProfilingGuanine Nucleotide Exchange FactorsLymphocytesMiceMolecular Sequence DataProtein BindingProtein IsoformsProtein Structure, TertiaryRac GTP-Binding ProteinsSequence AlignmentSubstrate Specificity
2004
VE-cadherin Links tRNA Synthetase Cytokine to Anti-angiogenic Function*
Tzima E, Reader JS, Irani-Tehrani M, Ewalt KL, Schwartz MA, Schimmel P. VE-cadherin Links tRNA Synthetase Cytokine to Anti-angiogenic Function*. Journal Of Biological Chemistry 2004, 280: 2405-2408. PMID: 15579907, DOI: 10.1074/jbc.c400431200.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acyl-tRNA SynthetasesAngiogenesis InhibitorsAnimalsAntigens, CDAortaBlotting, WesternCadherinsCattleCell MovementCells, CulturedCytokinesEndothelium, VascularEnzyme ActivationExtracellular Signal-Regulated MAP KinasesGap JunctionsGreen Fluorescent ProteinsImmunoprecipitationMicroscopy, ConfocalMicroscopy, FluorescenceNeovascularization, PathologicProtein BindingRecombinant ProteinsSignal TransductionTryptophan-tRNA LigaseVascular Endothelial Growth Factor AConceptsT2-TrpRS
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 ResearchA Fragment of Paxillin Binds the α4Integrin Cytoplasmic Domain (Tail) and Selectively Inhibits α4-Mediated Cell Migration*
Liu S, Kiosses WB, Rose DM, Slepak M, Salgia R, Griffin JD, Turner CE, Schwartz MA, Ginsberg MH. A Fragment of Paxillin Binds the α4Integrin Cytoplasmic Domain (Tail) and Selectively Inhibits α4-Mediated Cell Migration*. Journal Of Biological Chemistry 2002, 277: 20887-20894. PMID: 11919182, DOI: 10.1074/jbc.m110928200.Peer-Reviewed Original ResearchConceptsCytoplasmic domainPaxillin interactionCell migrationIntegrin-mediated cell adhesionIntegrin alpha subunitsEnhanced cell migrationPaxillin bindingFunctional responseFocal adhesionsCellular functionsPaxillinCardiac developmentAlanine substitutionsMutational analysisAdaptor moleculeAcid regionAlpha subunitBiological processesCell spreadingCellular responsesCell adhesionIntegrin subunitsSubunitsTernary complexFragmentsIntegrins 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
c-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
The Molecular Adapter SLP-76 Relays Signals from Platelet Integrin αIIbβ3 to the Actin Cytoskeleton*
Obergfell A, Judd B, del Pozo M, Schwartz M, Koretzky G, Shattil S. The Molecular Adapter SLP-76 Relays Signals from Platelet Integrin αIIbβ3 to the Actin Cytoskeleton*. Journal Of Biological Chemistry 2000, 276: 5916-5923. PMID: 11113155, DOI: 10.1074/jbc.m010639200.Peer-Reviewed Original ResearchMeSH KeywordsActinsAdaptor Proteins, Signal TransducingAnimalsBlood PlateletsCell AdhesionCell Cycle ProteinsCHO CellsCricetinaeCytoskeletonEnzyme PrecursorsFibrinogenHumansIntracellular Signaling Peptides and ProteinsPhosphoproteinsPhosphorylationPlatelet Glycoprotein GPIIb-IIIa ComplexProtein BindingProtein-Tyrosine KinasesProto-Oncogene ProteinsProto-Oncogene Proteins c-vavPseudopodiaRac GTP-Binding ProteinsSignal TransductionSyk KinaseConceptsSLP-76SLAP-130Lamellipodia formationSLP-76 functionAdhesion-dependent activationCHO cell adhesionCell expression systemSLP-76 phosphorylationChinese hamster ovary cell expression systemSLP-76 expressionSyk tyrosine kinasePlatelet integrin αIIbβ3Sites of adhesionRac effectorPAK kinasesActin cytoskeletonAdherent CHO cellsExchange factorActin rearrangementCytoskeletal reorganizationActin reorganizationTyrosine phosphorylationExpression systemCell spreadingTyrosine kinaseAdhesion 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