2021
Integrin-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 ResearchConceptsCellular 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
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 cellsActivationPathwayCells
2009
Focal adhesion kinase modulates activation of NF-κB by flow in endothelial cells
Petzold T, Orr AW, Hahn C, Jhaveri KA, Parsons JT, Schwartz MA. Focal adhesion kinase modulates activation of NF-κB by flow in endothelial cells. American Journal Of Physiology - Cell Physiology 2009, 297: c814-c822. PMID: 19587216, PMCID: PMC2770750, DOI: 10.1152/ajpcell.00226.2009.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell NucleusCells, CulturedEndothelial CellsEndothelium, VascularFocal Adhesion Protein-Tyrosine KinasesHydrogen PeroxideI-kappa B KinaseIntegrinsIntercellular Adhesion Molecule-1MiceNF-kappa BPhosphorylationProtein TransportRac GTP-Binding ProteinsReactive Oxygen SpeciesSignal TransductionStress, MechanicalTranscription Factor RelATumor Necrosis Factor-alphaConceptsFocal adhesion kinaseAdhesion kinaseNF-kappaBRac activationTranscriptional activityDependent genesEndothelial cellsIntegrin activationP65 NF-kappaB subunitDegradation of IkappaBReactive oxygen productionFluid shear stressNF-kappaB subunitsSerine 536Phosphorylation of p65Novel mechanismNF-kappaB activationKinaseNF-kappaB phosphorylationPhosphorylationActivationNF-κBOxygen productionHydrogen peroxideCells
2006
A mechanosensory complex that mediates the endothelial cell response to fluid shear stress
Tzima E, Irani‐Tehrani M, Kiosses W, Dejana E, Schultz D, Engelhardt B, Cao G, DeLisser H, Schwartz M. A mechanosensory complex that mediates the endothelial cell response to fluid shear stress. The FASEB Journal 2006, 20: a1378-a1378. DOI: 10.1096/fasebj.20.5.a1378-c.Peer-Reviewed Original ResearchPECAM-1-null miceDownstream inflammatory genesPECAM-1VE-cadherinDevelopment of atherosclerosisICAM-1 expressionNF-kB activationInitiation of atherosclerosisBlood pressureVascular remodelingHigh-affinity stateInflammatory genesNF-κBCell responsesEndothelial cell responsesNull miceMechanosensory complexIntegrin activationAffinity stateAtherosclerosisVEGFR2Heterologous cellsPathway upstreamActivationSrc family kinases
2005
αvβ3 Integrin Activation and Matrix Binding Mediate Cellular Responses to Mechanical Stretch.
Katsumi A, Matsushita T, Naoe T, Schwartz M. αvβ3 Integrin Activation and Matrix Binding Mediate Cellular Responses to Mechanical Stretch. Blood 2005, 106: 3689. DOI: 10.1182/blood.v106.11.3689.3689.Peer-Reviewed Original ResearchA 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 transductionPathwayMiceIntegrin Activation and Matrix Binding Mediate Cellular Responses to Mechanical Stretch*
Katsumi A, Naoe T, Matsushita T, Kaibuchi K, Schwartz MA. Integrin Activation and Matrix Binding Mediate Cellular Responses to Mechanical Stretch*. Journal Of Biological Chemistry 2005, 280: 16546-16549. PMID: 15760908, DOI: 10.1074/jbc.c400455200.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell AdhesionEnzyme ActivationEnzyme InhibitorsExtracellular MatrixExtracellular Signal-Regulated MAP KinasesIntegrin alphaVbeta3IntegrinsJNK Mitogen-Activated Protein KinasesLigandsMAP Kinase Kinase 4MiceMitogen-Activated Protein Kinase KinasesNIH 3T3 CellsPhosphatidylinositol 3-KinasesPhosphorylationProtein ConformationSignal TransductionStress, MechanicalTime FactorsConceptsIntegrin activationExtracellular matrix proteinsRole of integrinsConformational activationBiochemical signalsNIH3T3 cellsMolecular mechanismsCellular responsesMatrix proteinsExtracellular matrixCell growthMechanical stretch stimulationIntegrin alphavbeta3IntegrinsMechanical tensionMechanical stretchCritical determinantStretch stimulationActivationPhosphoinositolMechanotransductionJNKProteinApoptosisDifferentiation
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-3Protein
2000
Death Effector Domain Protein PEA-15 Potentiates Ras Activation of Extracellular Signal Receptor-activated Kinase by an Adhesion-independent Mechanism
Ramos J, Hughes P, Renshaw M, Schwartz M, Formstecher E, Chneiweiss H, Ginsberg M. Death Effector Domain Protein PEA-15 Potentiates Ras Activation of Extracellular Signal Receptor-activated Kinase by an Adhesion-independent Mechanism. Molecular Biology Of The Cell 2000, 11: 2863-2872. PMID: 10982386, PMCID: PMC14961, DOI: 10.1091/mbc.11.9.2863.Peer-Reviewed Original ResearchMeSH Keywords3T3 CellsAnimalsApoptosis Regulatory ProteinsCell AdhesionCell LineCHO CellsCricetinaeEnzyme ActivationGuanosine TriphosphateHumansIntracellular Signaling Peptides and ProteinsJNK Mitogen-Activated Protein KinasesMAP Kinase Kinase Kinase 1MiceMitogen-Activated Protein KinasesP38 Mitogen-Activated Protein KinasesPhosphoproteinsProtein Serine-Threonine KinasesRas ProteinsRecombinant Fusion ProteinsSignal TransductionConceptsPEA-15 expressionPEA-15ERK activationMitogen-activated protein kinase kinaseMitogen-activated protein kinase pathwayAdhesion-independent mechanismsRas-dependent mannerProtein kinase kinaseRegulation of apoptosisProtein kinase pathwayChinese hamster ovary cellsRas guanosineKinase kinaseRas activationSignal receptorHamster ovary cellsH-RasKinase pathwayERK activityIntegrin activationERK signalingAnchorage dependenceOncogenic processesOvary cellsApoptosis
1997
Suppression of Integrin Activation: A Novel Function of a Ras/Raf-Initiated MAP Kinase Pathway
Hughes P, Renshaw M, Pfaff M, Forsyth J, Keivens V, Schwartz M, Ginsberg M. Suppression of Integrin Activation: A Novel Function of a Ras/Raf-Initiated MAP Kinase Pathway. Cell 1997, 88: 521-530. PMID: 9038343, DOI: 10.1016/s0092-8674(00)81892-9.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCalcium-Calmodulin-Dependent Protein KinasesCell SizeCHO CellsCricetinaeCytoplasmDNA, ComplementaryEndoribonucleasesEnzyme ActivationExtracellular Matrix ProteinsFibronectinsFlow CytometryFungal ProteinsGene Expression Regulation, EnzymologicIntegrinsProtein BiosynthesisProtein Serine-Threonine KinasesProtein Structure, TertiaryProto-Oncogene ProteinsProto-Oncogene Proteins c-rafRas ProteinsRecombinant Fusion ProteinsTranscription, GeneticConceptsMAP kinase pathwayKinase pathwayIntegrin activationBeta-subunit cytoplasmic domainH-RasTranscription-independent functionsSubunit cytoplasmic domainERK MAP kinase pathwayIntegrin affinity stateCell adhesion receptorsIntegrin cell adhesion receptorsActivation of integrinsNegative feedback loopSmall GTPCytoplasmic domainEffector kinaseIntegrin phosphorylationRaf-1Novel functionIntegrin functionNegative regulatorAdhesion receptorsProtein synthesisMRNA transcriptionDistinct alpha