2020
Integrin-mediated adhesions in regulation of cellular senescence
Shin EY, Park JH, You ST, Lee CS, Won SY, Park JJ, Kim HB, Shim J, Soung NK, Lee OJ, Schwartz MA, Kim EG. Integrin-mediated adhesions in regulation of cellular senescence. Science Advances 2020, 6: eaay3909. PMID: 32494696, PMCID: PMC7202880, DOI: 10.1126/sciadv.aay3909.Peer-Reviewed Original ResearchConceptsClathrin-mediated endocytosisCellular senescenceG protein-coupled receptor kinasesProtein-coupled receptor kinasesElevated reactive oxygen species (ROS) productionIntegrin-mediated adhesionIntegrin endocytosisAmphiphysin 1Exchange factorReactive oxygen species productionReceptor kinaseOxygen species productionMolecular mechanismsCalpain cleavageSenescenceCell adhesionDirect competitionHuman fibroblastsGIT levelsSpecies productionΒPixNew therapeutic directionIntegrinsEndocytosisCentral role
2018
Talin as a mechanosensitive signaling hub
Goult BT, Yan J, Schwartz MA. Talin as a mechanosensitive signaling hub. Journal Of Cell Biology 2018, 217: 3776-3784. PMID: 30254032, PMCID: PMC6219721, DOI: 10.1083/jcb.201808061.Peer-Reviewed Original ResearchConceptsSignaling hubsExtracellular matrixRod domainTalin rod domainIntegrin β subunitsDifferent protein interactionsLong rod domainSwitch-like behaviorActin cytoskeletonCytoplasmic domainCytoplasmic proteinsProtein interactionsHelical bundleGlobular head domainTalin functionTransmembrane receptorsHelix bundleΒ-subunitHead domainIntegrin familyTalinCell adhesionIndividual domainsRecent evidenceDomain
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
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
Measuring mechanical tension across vinculin reveals regulation of focal adhesion dynamics
Grashoff C, Hoffman BD, Brenner MD, Zhou R, Parsons M, Yang MT, McLean MA, Sligar SG, Chen CS, Ha T, Schwartz MA. Measuring mechanical tension across vinculin reveals regulation of focal adhesion dynamics. Nature 2010, 466: 263-266. PMID: 20613844, PMCID: PMC2901888, DOI: 10.1038/nature09198.Peer-Reviewed Original ResearchConceptsFocal adhesionsFocal adhesion dynamicsMembrane cytoskeletal proteinsAdhesion dynamicsCell adhesion moleculeRegulatory mechanismsSpecific proteinsActin filamentsCell adhesionVinculinProteinMechanical tensionMechanical forcesRegulationPhysical forcesMolecular forcesAdhesionCellsVivoMechanotransductionPhysiologyNew biosensorFilamentsAbilityMigration
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
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
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 roleLocalizationK44AGTPasesMacropinosomesInvadopodiaModulation of DNA damage-induced apoptosis by cell adhesion is independently mediated by p53 and c-Abl
Truong T, Sun G, Doorly M, Wang JY, Schwartz MA. Modulation of DNA damage-induced apoptosis by cell adhesion is independently mediated by p53 and c-Abl. Proceedings Of The National Academy Of Sciences Of The United States Of America 2003, 100: 10281-10286. PMID: 12928501, PMCID: PMC193552, DOI: 10.1073/pnas.1635435100.Peer-Reviewed Original ResearchConceptsC-Abl/p73 pathwayDNA damageIntegrin ligationC-AblDNA damage-induced apoptosisC-Abl tyrosine kinaseCell adhesionExtracellular matrixDamage-induced apoptosisP73 pathwayCertain cell typesP53-negative tumor cellsProapoptotic transcription factorTranscription factorsTyrosine kinaseApoptotic responseDifferential utilizationCell typesDifferent tumor cell linesTumor cell linesTumor cellsP53 levelsCell linesSecond pathwayCell killing
2002
A 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 complexFragments
2001
Integrins and cell proliferationregulation of cyclin-dependent kinases via cytoplasmic signaling pathways
Schwartz M, Assoian R. Integrins and cell proliferationregulation of cyclin-dependent kinases via cytoplasmic signaling pathways. Journal Of Cell Science 2001, 114: 2553-2560. PMID: 11683383, DOI: 10.1242/jcs.114.14.2553.Peer-Reviewed Original ResearchConceptsCyclin-dependent kinasesG1 phase cyclin-dependent kinasesPhase cyclin-dependent kinasesCell cycle progressionCycle progressionCytoplasmic signaling pathwaysIntegrin-dependent signalsMammalian cellsGrowth factor receptorSignaling pathwaysERK pathwayCell adhesionExtracellular matrixDiverse arrayFactor receptorCyclin D1KinaseRegulationPathwayGrowth factorIntegrinsRecent advancesIntegrated controlReceptorsAdhesion
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
Regulation of the small GTP‐binding protein Rho by cell adhesion and the cytoskeleton
Ren X, Kiosses W, Alexander Schwartz M. Regulation of the small GTP‐binding protein Rho by cell adhesion and the cytoskeleton. The EMBO Journal 1999, 18: 578-585. PMID: 9927417, PMCID: PMC1171150, DOI: 10.1093/emboj/18.3.578.Peer-Reviewed Original ResearchConceptsFocal adhesionsRho activationRho activityExtracellular matrixSmall GTPProtein RhoLysophosphatidic acidStress fibersCell adhesionRho-dependent mannerActin stress fibersHigh Rho activitySwiss 3T3 cellsNegative feedback loopAdherent cellsCytoskeletal structuresSoluble factorsCytochalasin DRhoGTPPresence of serumCellsActivationRegulationAdhesion
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
1997
Growth factor activation of MAP kinase requires cell adhesion
Renshaw M, Ren X, Schwartz M. Growth factor activation of MAP kinase requires cell adhesion. The EMBO Journal 1997, 16: 5592-5599. PMID: 9312018, PMCID: PMC1170191, DOI: 10.1093/emboj/16.18.5592.Peer-Reviewed Original ResearchMeSH Keywords3T3 CellsAnimalsCalcium-Calmodulin-Dependent Protein KinasesCell AdhesionCell Transformation, NeoplasticEnzyme ActivationExtracellular Matrix ProteinsGenes, rasKineticsMAP Kinase Kinase Kinase 1MiceMitogen-Activated Protein Kinase 1Platelet-Derived Growth FactorProtein Serine-Threonine KinasesProto-Oncogene Proteins c-rafProto-OncogenesConceptsCell adhesionGrowth factor-regulated pathwaysMAP kinase ERK2Mutants of RasActivation of ERK2MAP kinase pathwayRas-transformed cellsGrowth factor activationExtracellular matrix proteinsSoluble growth factorsAnchorage-independent growthKinase ERK2Growth factorMAP kinaseOncogenic growthEndogenous RasKinase pathwayOncogenic activationMEK activityMatrix proteinsMajor regulatorERK2Factor activationRafMEK
1996
Integrin regulation of c-Abl tyrosine kinase activity and cytoplasmic–nuclear transport
Lewis J, Baskaran R, Taagepera S, Schwartz M, Wang J. Integrin regulation of c-Abl tyrosine kinase activity and cytoplasmic–nuclear transport. Proceedings Of The National Academy Of Sciences Of The United States Of America 1996, 93: 15174-15179. PMID: 8986783, PMCID: PMC26376, DOI: 10.1073/pnas.93.26.15174.Peer-Reviewed Original ResearchConceptsNuclear c-AblC-AblKinase activityC-Abl tyrosine kinase activityTyrosine kinaseCell adhesionCell cycle signalsCytoplasmic-nuclear transportExtracellular matrix protein fibronectinNonreceptor tyrosine kinaseCytoplasmic c-AblC-Abl activationC-Abl activityMatrix protein fibronectinTyrosine kinase activityC-abl protooncogeneMin of adhesionIntegrin regulationSubcellular localizationIntegrin signalsFocal contactsCytoplasmic poolTransient recruitmentSubcellular distributionProtein fibronectin
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 3Integrins: Emerging Paradigms of Signal Transduction
Schwartz M, Schaller M, Ginsberg M. Integrins: Emerging Paradigms of Signal Transduction. Annual Review Of Cell And Developmental Biology 1995, 11: 549-599. PMID: 8689569, DOI: 10.1146/annurev.cb.11.110195.003001.Peer-Reviewed Original Research
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