2012
The role of p21-activated kinase in the initiation of atherosclerosis
Jhaveri K, Debnath P, Chernoff J, Sanders J, Schwartz M. The role of p21-activated kinase in the initiation of atherosclerosis. BMC Cardiovascular Disorders 2012, 12: 55. PMID: 22824149, PMCID: PMC3489605, DOI: 10.1186/1471-2261-12-55.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAorta, ThoracicAortic DiseasesAtherosclerosisBiomechanical PhenomenaCells, CulturedDisease Models, AnimalEndothelial CellsFibronectinsGalectin 3ImmunohistochemistryInflammation MediatorsIntercellular Adhesion Molecule-1MaleMiceMice, Inbred C57BLMice, KnockoutP21-Activated KinasesRegional Blood FlowTranscription Factor RelBVascular Cell Adhesion Molecule-1ConceptsLesser curvatureNF-κB subunitsInflammatory activationEndothelial cellsAtherosclerosis-prone sitesPro-inflammatory functionsInflammatory marker expressionNormal chow dietArch of aortaInitiation of atherosclerosisInflammatory markersOverall inflammationChow dietInflammatory pathwaysYoung miceAtherosclerosis-susceptible regionsConclusionThese dataICAM-1VCAM-1NF-κBRelA NF-κB subunitMarker expressionLow levelsFibronectin depositionInflammationp21-Activated kinase 4 promotes prostate cancer progression through CREB
Park M, Lee H, Lee C, You S, Kim D, Park B, Kang M, Heo W, Shin E, Schwartz M, Kim E. p21-Activated kinase 4 promotes prostate cancer progression through CREB. Oncogene 2012, 32: 2475-2482. PMID: 22710715, DOI: 10.1038/onc.2012.255.Peer-Reviewed Original ResearchConceptsP21-activated kinase 4Prostate cancer progressionProstate cancerCancer progressionLNCaP-FGC cellsPromising therapeutic targetKinase 4Prostate cancer cellsDU145 prostate cancer cellsSpecific protein kinase A (PKA) inhibitorProtein kinase A (PKA) inhibitorElevation of cAMPNeuroendocrine differentiationNude miceTherapeutic targetActive PAK4Downstream effector pathwaysTumor progressionDecreased expressionTumor formationCancerCancer cellsPC-3ProgressionEffector pathways
2010
Matrix-Specific Protein Kinase A Signaling Regulates p21-Activated Kinase Activation by Flow in Endothelial Cells
Funk SD, Yurdagul A, Green JM, Jhaveri KA, Schwartz MA, Orr AW. Matrix-Specific Protein Kinase A Signaling Regulates p21-Activated Kinase Activation by Flow in Endothelial Cells. Circulation Research 2010, 106: 1394-1403. PMID: 20224042, PMCID: PMC2862370, DOI: 10.1161/circresaha.109.210286.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnti-Inflammatory AgentsBasement MembraneCattleCdc42 GTP-Binding ProteinCells, CulturedCyclic AMP-Dependent Protein KinasesEndothelial CellsEnzyme ActivationEnzyme ActivatorsHumansIloprostInflammationInflammation MediatorsInjections, IntraperitonealIntegrinsMaleMechanotransduction, CellularMiceMice, Inbred C57BLNF-kappa BP21-Activated KinasesPhosphorylationProtein Kinase InhibitorsPulsatile FlowRac GTP-Binding ProteinsRegional Blood FlowStress, MechanicalTime FactorsTransfectionConceptsInflammatory gene expressionNF-kappaB activationInflammatory signalingEndothelial cellsProstacyclin analogue iloprostBasement membrane proteinsBlood flow patternsPKA-dependent inhibitionInflammatory pathwaysAnalogue iloprostGene expressionKappaB activationNF-kappaB.Subendothelial extracellular matrixNuclear factorPAK activationBasement membrane
2009
The Subendothelial Extracellular Matrix Modulates JNK Activation by Flow
Hahn C, Orr AW, Sanders JM, Jhaveri KA, Schwartz MA. The Subendothelial Extracellular Matrix Modulates JNK Activation by Flow. Circulation Research 2009, 104: 995-1003. PMID: 19286608, PMCID: PMC2702158, DOI: 10.1161/circresaha.108.186486.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApolipoproteins EAtherosclerosisBasement MembraneCattleCell Culture TechniquesCells, CulturedCollagenDisease Models, AnimalEndothelial CellsEnzyme ActivationExtracellular MatrixFibronectinsHemorheologyInflammationIntegrinsJNK Mitogen-Activated Protein KinasesMiceMice, Inbred C57BLMice, KnockoutMitogen-Activated Protein Kinase KinasesOscillometryP21-Activated KinasesPhosphorylationRegional Blood FlowStress, Mechanical
2008
p21-Activated Kinase Signaling Regulates Oxidant-Dependent NF-&kgr;B Activation by Flow
Orr AW, Hahn C, Blackman BR, Schwartz MA. p21-Activated Kinase Signaling Regulates Oxidant-Dependent NF-&kgr;B Activation by Flow. Circulation Research 2008, 103: 671-679. PMID: 18669917, PMCID: PMC2697905, DOI: 10.1161/circresaha.108.182097.Peer-Reviewed Original ResearchConceptsNF-kappaB activationReactive oxygen speciesProinflammatory transcription factor nuclear factorTranscription factor nuclear factorInflammatory gene expressionNF-kappaB pathwayAbility of ROSP21-activated kinaseDisturbed blood flowBlood flowSensitivity of cellsNuclear factorEndothelial cellsROS productionActivationOxygen speciesCellsDisturbed flowGene expressionCollagen
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 cellsGIT1Blocking p21-activated Kinase Reduces Lipopolysaccharide-induced Acute Lung Injury by Preventing Polymorphonuclear Leukocyte Infiltration
Reutershan J, Stockton R, Zarbock A, Sullivan GW, Chang D, Scott D, Schwartz MA, Ley K. Blocking p21-activated Kinase Reduces Lipopolysaccharide-induced Acute Lung Injury by Preventing Polymorphonuclear Leukocyte Infiltration. American Journal Of Respiratory And Critical Care Medicine 2007, 175: 1027-1035. PMID: 17322107, PMCID: PMC1899271, DOI: 10.1164/rccm.200612-1822oc.Peer-Reviewed Original ResearchConceptsAcute lung injuryLung injuryPMN migrationPolymorphonuclear leukocytesAlveolar spaceLipopolysaccharide-induced lung injuryMurine lung injuryPolymorphonuclear leukocyte infiltrationLeukocyte-endothelial interactionsAlveolo-capillary membraneOxidative burstRole of PAKsLeukocyte infiltrationChemokine receptorsLung interstitiumMurine modelExcessive recruitmentPMN chemoattractantInjuryCytoskeletal actin polymerizationAdhesion moleculesCritical mediatorCell migrationAttractive targetPAK phosphorylationMatrix-specific p21-activated kinase activation regulates vascular permeability in atherogenesis
Orr AW, Stockton R, Simmers MB, Sanders JM, Sarembock IJ, Blackman BR, Schwartz MA. Matrix-specific p21-activated kinase activation regulates vascular permeability in atherogenesis. Journal Of Cell Biology 2007, 176: 719-727. PMID: 17312022, PMCID: PMC2064028, DOI: 10.1083/jcb.200609008.Peer-Reviewed Original ResearchConceptsP21-activated kinaseP21-activated kinase activationAtherosclerosis-prone regionsCell-cell junctionsBasement membrane proteinsMembrane proteinsPAK phosphorylationActivation of PAKKinase activationPAK activationEndothelial permeabilityFibronectinActivationSubendothelial monocytesVivoKinasePhosphorylationProteinVascular permeabilityAtherogenesisRecruitmentCells
2004
p21-activated Kinase Regulates Endothelial Permeability through Modulation of Contractility*
Stockton RA, Schaefer E, Schwartz MA. p21-activated Kinase Regulates Endothelial Permeability through Modulation of Contractility*. Journal Of Biological Chemistry 2004, 279: 46621-46630. PMID: 15333633, DOI: 10.1074/jbc.m408877200.Peer-Reviewed Original ResearchMeSH KeywordsActinsAnimalsBlotting, WesternCattleCell CommunicationCells, CulturedCytokinesCytoskeletonEndothelium, VascularEnzyme ActivationHumansInflammationIschemiaMicroscopy, FluorescenceMuscle ContractionMyosin Light ChainsP21-Activated KinasesPeptidesPhosphorylationProtein Serine-Threonine KinasesProtein TransportThrombinTime FactorsTransfectionUmbilical VeinsConceptsP21-activated kinaseClose cell-cell associationsEndothelial cell-cell junctionsCell-cell junctionsActin stress fibersCell-cell associationsSuitable drug targetsGrowth factorMyosin phosphorylationHuman umbilical vein endothelial cellsCentral regulatorStress fibersUmbilical vein endothelial cellsEndothelial cellsPAK activationDrug targetsVein endothelial cellsCell contractilityMultiple growth factorsParacellular poresEndothelial permeabilityPhosphorylationPathological processesPathological conditionsPotential role
2003
Differential αv integrin–mediated Ras-ERK signaling during two pathways of angiogenesis
Hood JD, Frausto R, Kiosses WB, Schwartz MA, Cheresh DA. Differential αv integrin–mediated Ras-ERK signaling during two pathways of angiogenesis. Journal Of Cell Biology 2003, 162: 933-943. PMID: 12952943, PMCID: PMC2172815, DOI: 10.1083/jcb.200304105.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsChick EmbryoEnzyme ActivationFibroblast Growth Factor 2Focal Adhesion Protein-Tyrosine KinasesIntegrin alphaVbeta3IntegrinsMitogen-Activated Protein KinasesNeovascularization, PhysiologicP21-Activated KinasesProtein Serine-Threonine KinasesProtein-Tyrosine KinasesProto-Oncogene Proteins c-rafRas ProteinsReceptors, VitronectinSignal TransductionSrc-Family KinasesVascular Endothelial Growth Factor AConceptsPathways of angiogenesisC-RafDistinct vascular responsesDownstream of RasUpstream of RasC-Raf activationC-Raf activityKinase-dependent phosphorylationRas-ERK pathwayInhibition of FAKVascular responsesPhosphorylation/activationSignal-related kinaseEndothelial cell survivalSerine 338Blood vesselsRas-ERKActive RAChick chorioallantoic membraneRA activityAngiogenesisERK activityRetroviral deliveryVEGFCell survivalGuanine Exchange-Dependent and -Independent Effects of Vav1 on Integrin-Induced T Cell Spreading
del Pozo MA, Schwartz MA, Hu J, Kiosses WB, Altman A, Villalba M. Guanine Exchange-Dependent and -Independent Effects of Vav1 on Integrin-Induced T Cell Spreading. The Journal Of Immunology 2003, 170: 41-47. PMID: 12496381, DOI: 10.4049/jimmunol.170.1.41.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCdc42 GTP-Binding ProteinCell Cycle ProteinsCell SizeCells, CulturedDrug SynergismEnzyme ActivationFibronectinsGuanine Nucleotide Exchange FactorsHumansHybridomasIntegrinsJNK Mitogen-Activated Protein KinasesJurkat CellsMiceMitogen-Activated Protein KinasesP21-Activated KinasesPhosphorylationProtein Serine-Threonine KinasesProto-Oncogene ProteinsProto-Oncogene Proteins c-vavRac GTP-Binding ProteinsT-Lymphocytes
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
2000
Adhesion 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
A Role for P21-Activated Kinase in Endothelial Cell Migration
Kiosses W, Daniels R, Otey C, Bokoch G, Schwartz M. A Role for P21-Activated Kinase in Endothelial Cell Migration. Journal Of Cell Biology 1999, 147: 831-844. PMID: 10562284, PMCID: PMC2156168, DOI: 10.1083/jcb.147.4.831.Peer-Reviewed Original ResearchActininAnimalsCell AdhesionCell LineCell MovementCOS CellsEndothelium, VascularGreen Fluorescent ProteinsLuminescent ProteinsMicrocirculationMicroscopy, VideoModels, BiologicalMyosin Light ChainsP21-Activated KinasesPhosphorylationProtein Serine-Threonine KinasesRecombinant Fusion ProteinsRecombinant ProteinsSrc Homology DomainsTransfectionVinculin
1998
Activation of Rac and Cdc42 by Integrins Mediates Cell Spreading
Price L, Leng J, Schwartz M, Bokoch G. Activation of Rac and Cdc42 by Integrins Mediates Cell Spreading. Molecular Biology Of The Cell 1998, 9: 1863-1871. PMID: 9658176, PMCID: PMC25428, DOI: 10.1091/mbc.9.7.1863.Peer-Reviewed Original Research