2022
Integrin Conformational Dynamics and Mechanotransduction
Kolasangiani R, Bidone T, Schwartz M. Integrin Conformational Dynamics and Mechanotransduction. Cells 2022, 11: 3584. PMID: 36429013, PMCID: PMC9688440, DOI: 10.3390/cells11223584.Peer-Reviewed Original ResearchConceptsCell-cell adhesionCell-extracellular matrixExtracellular ligandsIntegrin affinityConformational dynamicsIntegrin familyConformational statesConformational transitionTissue integrityCell functionCentral mediatorRemarkable convergenceMechanical forcesForce transmissionCytoskeletonMechanotransductionAdhesionFirm adhesionUnanswered questionsIntegrinsNew informationPathwayLigands
2021
Altered endocytosis in cellular senescence
Shin EY, Soung NK, Schwartz MA, Kim EG. Altered endocytosis in cellular senescence. Ageing Research Reviews 2021, 68: 101332. PMID: 33753287, PMCID: PMC8131247, DOI: 10.1016/j.arr.2021.101332.Peer-Reviewed Original ResearchEarly events in endothelial flow sensing
Tanaka K, Joshi D, Timalsina S, Schwartz MA. Early events in endothelial flow sensing. Cytoskeleton 2021, 78: 217-231. PMID: 33543538, DOI: 10.1002/cm.21652.Peer-Reviewed Original ResearchConceptsFluid shear stressLymphatic endothelial cellsEndothelial cellsCytoskeletal pathwaysVascular morphogenesisBiochemical signalsGene expressionEC phenotypeLymphatic fluid flowEarly eventsPhysiologyImmediate mechanismPrimary mechanismRecent advancesMorphogenesisMechanotransductionSignalingPhenotypePathwayMechanismExpressionFlow sensingCellsImportant questions
2019
MKL1-actin pathway restricts chromatin accessibility and prevents mature pluripotency activation
Hu X, Liu ZZ, Chen X, Schulz VP, Kumar A, Hartman AA, Weinstein J, Johnston JF, Rodriguez EC, Eastman AE, Cheng J, Min L, Zhong M, Carroll C, Gallagher PG, Lu J, Schwartz M, King MC, Krause DS, Guo S. MKL1-actin pathway restricts chromatin accessibility and prevents mature pluripotency activation. Nature Communications 2019, 10: 1695. PMID: 30979898, PMCID: PMC6461646, DOI: 10.1038/s41467-019-09636-6.Peer-Reviewed Original ResearchConceptsCell fate reprogrammingChromatin accessibilityActin cytoskeletonSomatic cell reprogrammingPluripotency transcription factorsGlobal chromatin accessibilityGenomic accessibilityCytoskeleton (LINC) complexCell reprogrammingCytoskeletal genesTranscription factorsReprogrammingPluripotencyChromatinCytoskeletonMKL1Unappreciated aspectPathwayNuclear volumeNucleoskeletonSUN2CellsActivationGenesExpression
2016
Endothelial fluid shear stress sensing in vascular health and disease
Baeyens N, Bandyopadhyay C, Coon BG, Yun S, Schwartz MA. Endothelial fluid shear stress sensing in vascular health and disease. Journal Of Clinical Investigation 2016, 126: 821-828. PMID: 26928035, PMCID: PMC4767335, DOI: 10.1172/jci83083.Peer-Reviewed Original ResearchConceptsNormal morphogenesisBiochemical signalsGene expressionSame pathwayFluid shear stressCell behaviorSpecialized mechanismsMorphogenesisPathwayPathological conditionsEndothelial cellsVascular physiologyVascular systemBasic mechanismsRecent advancesFlow signalingSignalingMechanismAdult lifePhysiologyExpression
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 Assays
2013
Integrins in mechanotransduction
Ross TD, Coon BG, Yun S, Baeyens N, Tanaka K, Ouyang M, Schwartz MA. Integrins in mechanotransduction. Current Opinion In Cell Biology 2013, 25: 613-618. PMID: 23797029, PMCID: PMC3757118, DOI: 10.1016/j.ceb.2013.05.006.Peer-Reviewed Original ResearchConceptsMolecular mechanismsIntegrin-mediated adhesionImportant regulatory eventActin cytoskeletonRegulatory eventsExtracellular matrixNormal physiologyCell functionMajor insightsCentral roleCellsRecent advancesCytoskeletonEffect of forceMechanotransductionAdhesionIntegrinsPathwayPhysiologyMechanismRecent work
2011
JNK2 Promotes Endothelial Cell Alignment under Flow
Hahn C, Wang C, Orr AW, Coon BG, Schwartz MA. JNK2 Promotes Endothelial Cell Alignment under Flow. PLOS ONE 2011, 6: e24338. PMID: 21909388, PMCID: PMC3164210, DOI: 10.1371/journal.pone.0024338.Peer-Reviewed Original ResearchConceptsMitogen-activated protein kinase c-Jun N-terminal kinaseProtein kinase c-Jun N-terminal kinaseC-Jun N-terminal kinaseActin stress fibersN-terminal kinaseFocal adhesionsBasement membrane proteinsMembrane proteinsLaminar shear stressStress fibersGene expressionJNK activityIntegrin activationJNK2 activationEndothelial cell alignmentJNK activationActivated JNKExtracellular matrixInflammatory gene expressionCell alignmentUnexpected connectionEndothelial cellsActivationPathwayCellsDynamic molecular processes mediate cellular mechanotransduction
Hoffman BD, Grashoff C, Schwartz MA. Dynamic molecular processes mediate cellular mechanotransduction. Nature 2011, 475: 316-323. PMID: 21776077, PMCID: PMC6449687, DOI: 10.1038/nature10316.Peer-Reviewed Original ResearchConceptsCell adhesion complexesDistinct signaling pathwaysTransduction of forceDynamic molecular processesEmbryonic developmentCellular mechanotransductionPlasma membraneBiochemical signalsAdult physiologySignaling pathwaysCellular responsesSubcellular structuresMolecular processesNumerous diseasesMechanical forcesMuscular dystrophyCytoskeletonTransductionMechanotransductionPathwayPhysiologyDisassemblyRecent workMembraneAssembly
2010
Integrins and Extracellular Matrix in Mechanotransduction
Schwartz MA. Integrins and Extracellular Matrix in Mechanotransduction. Cold Spring Harbor Perspectives In Biology 2010, 2: a005066. PMID: 21084386, PMCID: PMC2982167, DOI: 10.1101/cshperspect.a005066.Peer-Reviewed Original ResearchConceptsIntegrin-mediated adhesionExtracellular matrixCytoskeletal linker proteinExtracellular matrix fibrilsIntracellular actin filamentsLinker proteinGenetic programActin filamentsExtracellular structuresCell survivalMatrix fibrilsIntegrinsCell functionCurrent knowledgeMechanotransductionMechanical forcesTransmits forcesIntracellularAdhesionCellsCytoskeletonProteinRegulationPathwayEnvironmental forces
2008
The Role of Cellular Adaptation to Mechanical Forces in Atherosclerosis
Hahn C, Schwartz MA. The Role of Cellular Adaptation to Mechanical Forces in Atherosclerosis. Arteriosclerosis Thrombosis And Vascular Biology 2008, 28: 2101-2107. PMID: 18787190, PMCID: PMC2737679, DOI: 10.1161/atvbaha.108.165951.Peer-Reviewed Original ResearchConceptsDisease progressionChronic inflammatory diseaseSystemic risk factorsInflammatory pathwaysInflammatory diseasesRisk factorsRegions of arteriesPlaque formationAtherosclerosisProgressionCellular adaptationPotential mechanosensorsAdaptive responseCellular responsesGene expressionHyperlipidemiaSubsequent changesSmokingDiabetesArteryPathwayDiseaseVasculatureResponseCell adhesion receptors in mechanotransduction
Schwartz MA, DeSimone DW. Cell adhesion receptors in mechanotransduction. Current Opinion In Cell Biology 2008, 20: 551-556. PMID: 18583124, PMCID: PMC2581799, DOI: 10.1016/j.ceb.2008.05.005.Peer-Reviewed Original ResearchConceptsAdhesion receptorsCell fate decisionsCadherin-mediated adhesionCell adhesion receptorsFate decisionsMorphogenetic movementsTissue-level responsesCultured cellsExtracellular matrixMechanotransductionLevel responseCellsCytoskeletonCadherinReceptorsOrganismsAdhesionIntegrinsPathwayMechanical stimulationIntracellularMechanismMechanical stressResponseCentral mechanisms
2007
Arf6 and microtubules in adhesion-dependent trafficking of lipid rafts
Balasubramanian N, Scott DW, Castle JD, Casanova JE, Schwartz MA. Arf6 and microtubules in adhesion-dependent trafficking of lipid rafts. Nature Cell Biology 2007, 9: 1381-1391. PMID: 18026091, PMCID: PMC2715295, DOI: 10.1038/ncb1657.Peer-Reviewed Original ResearchConceptsPlasma membraneLipid raftsAnchorage-dependent signalingArf6-dependent mannerCaveolin-dependent internalizationSmall GTPase Arf6Microtubule-dependent traffickingIntegrin-mediated adhesionRecycling endosomesGTPase Arf6Membrane raftsDetachment of cellsCell spreadingF-actinRaftsArf6MicrotubulesEndosomesRac1TraffickingMembraneCellsEndocytosisSignalingPathwayRac, membrane heterogeneity, caveolin and regulation of growth by integrins
Del Pozo MA, Schwartz MA. Rac, membrane heterogeneity, caveolin and regulation of growth by integrins. Trends In Cell Biology 2007, 17: 246-250. PMID: 17363257, DOI: 10.1016/j.tcb.2007.03.001.Peer-Reviewed Original ResearchConceptsCholesterol-enriched membrane domainsAnchorage dependenceGrowth regulatory pathwaysRegulation of growthBlocks cell proliferationCancer cell invasionMembrane domainsRegulatory pathwaysCaveolin-1Cell invasionTyr-14Membrane heterogeneityNon-adherent cellsMultiple pathwaysCell proliferationBinding sitesRacImportant mechanismIntegrinsPathwayCaveolinCellsPtdInsCaveolaeEndocytosis
2005
A mechanosensory complex that mediates the endothelial cell response to fluid shear stress
Tzima E, Irani-Tehrani M, Kiosses WB, Dejana E, Schultz DA, Engelhardt B, Cao G, DeLisser H, Schwartz MA. A mechanosensory complex that mediates the endothelial cell response to fluid shear stress. Nature 2005, 437: 426-431. PMID: 16163360, DOI: 10.1038/nature03952.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, CDCadherinsCattleCell AdhesionCells, CulturedEndothelial CellsFemaleGene DeletionMechanotransduction, CellularMiceMice, KnockoutMultiprotein ComplexesNF-kappa BPlatelet Endothelial Cell Adhesion Molecule-1RatsStress, MechanicalVascular Endothelial Growth Factor Receptor-2ConceptsDownstream inflammatory genesPECAM-1 knockout miceVascular endothelial cell cadherinVascular remodellingHigh-affinity stateInflammatory genesNF-κBVascular homeostasisEndothelial cell responsesCell responsesMechanosensory complexPECAM-1Heterologous cellsPathway upstreamCardiac developmentIntegrin activationAtherogenesisMechanism of transductionPathwayMicePhospho-caveolin-1 mediates integrin-regulated membrane domain internalization
del Pozo MA, Balasubramanian N, Alderson NB, Kiosses WB, Grande-García A, Anderson RG, Schwartz MA. Phospho-caveolin-1 mediates integrin-regulated membrane domain internalization. Nature Cell Biology 2005, 7: 901-908. PMID: 16113676, PMCID: PMC1351395, DOI: 10.1038/ncb1293.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCaveolaeCaveolin 1CaveolinsCell AdhesionCell ProliferationDynamin IIEndocytosisExtracellular MatrixExtracellular Signal-Regulated MAP KinasesFocal AdhesionsIntegrinsMembrane MicrodomainsMiceMice, KnockoutMicroscopy, Electron, TransmissionNeoplasm InvasivenessNeoplasmsNIH 3T3 CellsPhosphatidylinositol 3-KinasesPhosphorylationRac GTP-Binding ProteinsConceptsCaveolin-1Cholesterol-enriched membrane microdomainsPhosphatidylinositol-3-OH kinaseCell detachmentNovel molecular mechanismCholesterol-rich domainsInhibition of ERKMembrane microdomainsFocal adhesionsDynamin 2Plasma membraneMolecular mechanismsTumor suppressionTyr-14Multiple pathwaysNormal cellsInternalizationERKRacPathwayCaveolaeKinasePhosphorylationAdhesionMicrodomains
2003
Cell Migration: Integrating Signals from Front to Back
Ridley AJ, Schwartz MA, Burridge K, Firtel RA, Ginsberg MH, Borisy G, Parsons JT, Horwitz AR. Cell Migration: Integrating Signals from Front to Back. Science 2003, 302: 1704-1709. PMID: 14657486, DOI: 10.1126/science.1092053.Peer-Reviewed Original Research
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
Cell Adhesion Regulates Ubiquitin-mediated Degradation of the Platelet-derived Growth Factor Receptor β*
Baron V, Schwartz M. Cell Adhesion Regulates Ubiquitin-mediated Degradation of the Platelet-derived Growth Factor Receptor β*. Journal Of Biological Chemistry 2000, 275: 39318-39323. PMID: 11007771, DOI: 10.1074/jbc.m003618200.Peer-Reviewed Original ResearchMeSH KeywordsAdenoviridaeAnimalsBlotting, WesternCell AdhesionCell DivisionCell LineCells, CulturedCysteine EndopeptidasesDose-Response Relationship, DrugDown-RegulationDynaminsEmbryo, MammalianEnzyme InhibitorsFibroblastsFibronectinsGTP PhosphohydrolasesHumansLigandsLysosomesMiceMultienzyme ComplexesPhosphorylationProteasome Endopeptidase ComplexProtein-Tyrosine KinasesReceptors, Platelet-Derived Growth FactorTemperatureTime FactorsTrypsinTyrphostinsUbiquitinsConceptsUbiquitin-dependent pathwayIntegrin-mediated adhesionPlatelet-derived growth factor receptor βPlatelet-derived growth factor receptor betaTyrosine kinase activityGrowth factor receptor βGrowth factor receptor betaProteasome pathwayDetachment of cellsReceptor autophosphorylationKinase activityCellular desensitizationPrimary fibroblastsExtracellular matrixCell detachmentAutophosphorylationProtein levelsCell linesPDGFGrowth factorReceptor betaReceptor βCellsPathwayRecent studies
1996
Transformation by Rho exchange factor oncogenes is mediated by activation of an integrin‐dependent pathway.
Schwartz M, Toksoz D, Khosravi‐Far R. Transformation by Rho exchange factor oncogenes is mediated by activation of an integrin‐dependent pathway. The EMBO Journal 1996, 15: 6525-6530. PMID: 8978679, PMCID: PMC452477, DOI: 10.1002/j.1460-2075.1996.tb01043.x.Peer-Reviewed Original ResearchMeSH Keywords3T3 CellsA Kinase Anchor ProteinsAdaptor Proteins, Signal TransducingAnimalsCalciumCell DivisionCell Transformation, NeoplasticGTP-Binding ProteinsGuanine Nucleotide Exchange FactorsIntegrinsKineticsMiceMinor Histocompatibility AntigensModels, BiologicalOncogenesPhosphatidylinositol 4,5-DiphosphateProto-Oncogene ProteinsRetroviridae Proteins, OncogenicRho GTP-Binding ProteinsSignal TransductionThrombinConceptsConstitutive activationCell growthIntegrin signal transductionSmall GTPase RhoIntegrin-dependent pathwaySignal transductionSignaling eventsGrowth factor receptorGTPase RhoSerum-dependent growthAnchorage independenceFactor receptorPathwayOncogeneUncontrolled growthRhoActivationImportant mediatorTumor cellsGrowthTransductionTransmit signalDblGrowth resultsAnchorage