2023
TLN1 contains a cancer-associated cassette exon that alters talin-1 mechanosensitivity
Gallego-Paez L, Edwards W, Chanduri M, Guo Y, Koorman T, Lee C, Grexa N, Derksen P, Yan J, Schwartz M, Mauer J, Goult B. TLN1 contains a cancer-associated cassette exon that alters talin-1 mechanosensitivity. Journal Of Cell Biology 2023, 222: e202209010. PMID: 36880935, PMCID: PMC9997659, DOI: 10.1083/jcb.202209010.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingExonsHumansMechanotransduction, CellularNeoplasmsTalinConceptsExon 17bTerminal FERM domainVinculin bindingFERM domainSwitch domainAdhesion dynamicsCassette exonsSplicing analysisAdapter proteinTLN1Single isoformIsoform switchTalin-1Amino acidsFrame insertionExonsBiochemical analysisIsoformsProteinExon 17CytoskeletonGenesMechanotransductionDomainIntegrins
2021
Epistatic interaction of PDE4DIP and DES mutations in familial atrial fibrillation with slow conduction
Ziki M, Bhat N, Neogi A, Driscoll TP, Ugwu N, Liu Y, Smith E, Abboud JM, Chouairi S, Schwartz MA, Akar JG, Mani A. Epistatic interaction of PDE4DIP and DES mutations in familial atrial fibrillation with slow conduction. Human Mutation 2021, 42: 1279-1293. PMID: 34289528, PMCID: PMC8434967, DOI: 10.1002/humu.24265.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAtrial FibrillationCardiomyopathy, DilatedCytoskeletal ProteinsDesminExome SequencingHumansMutationPenetranceConceptsEarly-onset atrial fibrillationAtrial fibrillationHeart blockFamilial atrial fibrillationSlow conductionDES mutationsSlow atrial fibrillationWhole-exome sequencingConduction diseaseIsoproterenol stimulationExome sequencingGenetic causePathogenic mutationsPDE4DIPReduced colocalizationHigh penetranceGenetic screeningUnrelated kindredsFibrillationPKA phosphorylationDesmin geneEpistatic interactionsT substitutionKindredsPDE4D
2015
Targeting NCK-Mediated Endothelial Cell Front-Rear Polarity Inhibits Neovascularization
Dubrac A, Genet G, Ola R, Zhang F, Pibouin-Fragner L, Han J, Zhang J, Thomas JL, Chedotal A, Schwartz MA, Eichmann A. Targeting NCK-Mediated Endothelial Cell Front-Rear Polarity Inhibits Neovascularization. Circulation 2015, 133: 409-421. PMID: 26659946, PMCID: PMC4729599, DOI: 10.1161/circulationaha.115.017537.Peer-Reviewed Original ResearchConceptsFront-rear polaritySprouting angiogenesisSignal integration mechanismImportant drug targetsNck adaptorsCytoskeletal dynamicsEndothelial cell migrationEmbryonic developmentAngiogenesis defectsPAK2 activationVessel sproutsNumber of diseasesBlood vessel growthDrug targetsCell migrationPostnatal retinaAngiogenic growthNckNck1AdaptorVessel growthKey processesEndothelial cellsPathological ocular neovascularizationInhibits neovascularizationEndothelial-to-mesenchymal transition drives atherosclerosis progression
Chen PY, Qin L, Baeyens N, Li G, Afolabi T, Budatha M, Tellides G, Schwartz MA, Simons M. Endothelial-to-mesenchymal transition drives atherosclerosis progression. Journal Of Clinical Investigation 2015, 125: 4514-4528. PMID: 26517696, PMCID: PMC4665771, DOI: 10.1172/jci82719.Peer-Reviewed Original ResearchConceptsProgression of atherosclerosisTGF-β signalingFGF receptor 1Left main coronary arteryMesenchymal transitionFGFR1 expressionDevelopment of EndMTMain coronary arteryTotal plaque burdenHigh-fat dietCultured human endothelial cellsDouble knockout miceEndothelial-specific deletionEarly time pointsCoronary atherosclerosisCoronary diseaseHuman endothelial cellsAtherosclerosis progressionPlaque burdenAtherosclerotic miceCoronary arteryInflammatory cytokinesAtherosclerotic lesionsNeointima formationClinical relevance
2007
Induction of Vascular Permeability: βPIX and GIT1 Scaffold the Activation of Extracellular Signal-regulated Kinase by PAK
Stockton R, Reutershan J, Scott D, Sanders J, Ley K, Schwartz MA. Induction of Vascular Permeability: βPIX and GIT1 Scaffold the Activation of Extracellular Signal-regulated Kinase by PAK. Molecular Biology Of The Cell 2007, 18: 2346-2355. PMID: 17429073, PMCID: PMC1877103, DOI: 10.1091/mbc.e06-07-0584.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAnimalsCapillary PermeabilityCattleCell Cycle ProteinsCells, CulturedEndothelial CellsEnzyme ActivationExtracellular Signal-Regulated MAP KinasesGuanine Nucleotide Exchange FactorsHumansInflammationLipopolysaccharidesLungMiceP21-Activated KinasesPeptidesProtein Serine-Threonine KinasesRho Guanine Nucleotide Exchange FactorsConceptsP21-activated kinaseMitogen-activated protein kinase kinaseEndothelial cell-cell junctionsExtracellular signal-regulated kinaseCell-cell junctionsProtein kinase kinaseMyosin light chain phosphorylationLight chain phosphorylationSignal-regulated kinaseCell-permeant peptideActivation of ERKKinase kinaseExtracellular signalsPAK functionChain phosphorylationCritical regulatorKinaseCell contractilityCell typesCultured endothelial cellsPhosphorylationMouse lung injury modelMyosin phosphorylationEndothelial cellsGIT1
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 Research
2001
Integrin-mediated mechanotransduction requires its dynamic interaction with specific extracellular matrix (ECM) ligands
Jalali S, del Pozo M, Chen K, Miao H, Li Y, Schwartz M, Shyy J, Chien S. Integrin-mediated mechanotransduction requires its dynamic interaction with specific extracellular matrix (ECM) ligands. Proceedings Of The National Academy Of Sciences Of The United States Of America 2001, 98: 1042-1046. PMID: 11158591, PMCID: PMC14705, DOI: 10.1073/pnas.98.3.1042.Peer-Reviewed Original ResearchAdaptor Proteins, Signal TransducingAdaptor Proteins, Vesicular TransportAntigens, CDCells, CulturedCollagenEndothelium, VascularExtracellular MatrixExtracellular Matrix ProteinsFibrinogenFibronectinsHumansIntegrin beta1Integrin beta3IntegrinsJNK Mitogen-Activated Protein KinasesLamininLigandsMitogen-Activated Protein KinasesPlatelet Membrane GlycoproteinsProteinsReceptors, VitronectinShc Signaling Adaptor ProteinsSignal TransductionSrc Homology 2 Domain-Containing, Transforming Protein 1Stress, MechanicalUmbilical VeinsVitronectin
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 kinaseThe c-Abl tyrosine kinase contributes to the transient activation of MAP kinase in cells plated on fibronectin
Renshaw M, Lewis J, Schwartz M. The c-Abl tyrosine kinase contributes to the transient activation of MAP kinase in cells plated on fibronectin. Oncogene 2000, 19: 3216-3219. PMID: 10918577, DOI: 10.1038/sj.onc.1203667.Peer-Reviewed Original ResearchMeSH Keywords3T3 CellsAdaptor Proteins, Signal TransducingAnimalsCell Culture TechniquesEnzyme ActivationFibronectinsFocal Adhesion Kinase 1Focal Adhesion Protein-Tyrosine KinasesGRB2 Adaptor ProteinMAP Kinase Signaling SystemMiceMitogen-Activated Protein Kinase 1Mitogen-Activated Protein KinasesProteinsProtein-Tyrosine KinasesProto-Oncogene Proteins c-abl
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 resultsAnchorageInvolvement of the Small GTPase Rho in Integrin-mediated Activation of Mitogen-activated Protein Kinase*
Renshaw M, Toksoz D, Schwartz M. Involvement of the Small GTPase Rho in Integrin-mediated Activation of Mitogen-activated Protein Kinase*. Journal Of Biological Chemistry 1996, 271: 21691-21694. PMID: 8702960, DOI: 10.1074/jbc.271.36.21691.Peer-Reviewed Original ResearchA Kinase Anchor ProteinsAdaptor Proteins, Signal TransducingADP Ribose TransferasesAnimalsBotulinum ToxinsCalcium-Calmodulin-Dependent Protein KinasesCation Exchange ResinsCell AdhesionCell LineEnzyme ActivationFibronectinsGTP-Binding ProteinsIntegrinsLipidsMinor Histocompatibility AntigensMitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3Mitogen-Activated Protein KinasesProto-Oncogene ProteinsRho GTP-Binding ProteinsTetradecanoylphorbol AcetateTransfection