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
2011
Myosin II directly binds and inhibits Dbl family guanine nucleotide exchange factors
Lee C, Shin E, Hong J, Schwartz M, Kim E. Myosin II directly binds and inhibits Dbl family guanine nucleotide exchange factors. The FASEB Journal 2011, 25: 930.9-930.9. DOI: 10.1096/fasebj.25.1_supplement.930.9.Peer-Reviewed Original ResearchFocal complex formationDbl family guanineMyosin IIExchange factorFamily guanineATPase activityNonmuscle myosin IIComplex formationSpatiotemporal regulationGEF activityAdhesion dynamicsCdc42 GTPasesRho GTPasesCdc42 activationLamellipodial protrusionCell protrusionsActomyosin contractionGEFFunctional linkNIH3T3 fibroblastsCell migrationGTPasesCatalytic siteHomology modulesGuanine
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
2007
A fluorescence resonance energy transfer activation sensor for Arf6
Hall B, McLean MA, Davis K, Casanova JE, Sligar SG, Schwartz MA. A fluorescence resonance energy transfer activation sensor for Arf6. Analytical Biochemistry 2007, 374: 243-249. PMID: 18162163, PMCID: PMC2277471, DOI: 10.1016/j.ab.2007.11.032.Peer-Reviewed Original ResearchConceptsMembrane targetingPlatelet-derived growth factorARF6 activationFluorescent proteinGreen fluorescent protein derivativesNormal membrane targetingRas family GTPasesDownstream effector proteinsSmall GTPase Arf6Small GTPase activationFluorescent reporter proteinFluorescent protein derivativesEffector proteinsExchange factorGTPase Arf6Effector domainReporter proteinGTPase activationRac activationN-terminusArf6Intact cellsCell migrationNormal regulationProtein
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
The Novel Cdc42 Guanine Nucleotide Exchange Factor, Zizimin1, Dimerizes via the Cdc42-binding CZH2 Domain*
Meller N, Irani-Tehrani M, Ratnikov BI, Paschal BM, Schwartz MA. The Novel Cdc42 Guanine Nucleotide Exchange Factor, Zizimin1, Dimerizes via the Cdc42-binding CZH2 Domain*. Journal Of Biological Chemistry 2004, 279: 37470-37476. PMID: 15247287, DOI: 10.1074/jbc.m404535200.Peer-Reviewed Original ResearchConceptsExchange factorCdc42 Guanine Nucleotide Exchange FactorGuanine nucleotide exchange factorsRho family small GTPasesDomain-containing proteinsNucleotide exchange factorsMultiple cellular processesCDM proteinsCZH proteinsSmall GTPasesRho proteinsCellular processesCdc42 activationRho-GEFsCdc42Acid regionHomology analysisCritical regulatorZizimin1ProteinPositive cooperativityMutation analysisDimerizationDock180GTPases
2002
Effects 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
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 kinase