2016
Defective fluid shear stress mechanotransduction mediates hereditary hemorrhagic telangiectasia
Baeyens N, Larrivée B, Ola R, Hayward-Piatkowskyi B, Dubrac A, Huang B, Ross TD, Coon BG, Min E, Tsarfati M, Tong H, Eichmann A, Schwartz MA. Defective fluid shear stress mechanotransduction mediates hereditary hemorrhagic telangiectasia. Journal Of Cell Biology 2016, 214: 807-816. PMID: 27646277, PMCID: PMC5037412, DOI: 10.1083/jcb.201603106.Peer-Reviewed Original ResearchActivin Receptors, Type IIArteriovenous MalformationsArteriovenous Shunt, SurgicalBone Morphogenetic ProteinsCell ProliferationEndoglinEndothelial CellsGene DeletionHEK293 CellsHemorheologyHuman Umbilical Vein Endothelial CellsHumansMechanotransduction, CellularPericytesRegional Blood FlowRetinaSignal TransductionSolubilityStress, MechanicalTelangiectasia, Hereditary HemorrhagicRal-Arf6 crosstalk regulates Ral dependent exocyst trafficking and anchorage independent growth signalling
Pawar A, Meier JA, Dasgupta A, Diwanji N, Deshpande N, Saxena K, Buwa N, Inchanalkar S, Schwartz MA, Balasubramanian N. Ral-Arf6 crosstalk regulates Ral dependent exocyst trafficking and anchorage independent growth signalling. Cellular Signalling 2016, 28: 1225-1236. PMID: 27269287, PMCID: PMC4973806, DOI: 10.1016/j.cellsig.2016.05.023.Peer-Reviewed Original ResearchMeSH KeywordsADP-Ribosylation Factor 6ADP-Ribosylation FactorsAnimalsCell AdhesionCell Line, TumorCell ProliferationCell Transformation, NeoplasticEmbryo, MammalianExocytosisExtracellular Signal-Regulated MAP KinasesFibroblastsHumansMembrane MicrodomainsMiceProtein TransportRal GTP-Binding ProteinsSignal TransductionConceptsARF6 activationRegulatory crosstalkActive RalIntegrin-dependent regulationOncogenic H-RasIndependent growthIntegrin-dependent activationAdhesion-dependent pathwayKey downstream mediatorSmall GTPase RalActive RalABladder cancer T24 cellsDependent traffickingRal functionIsoforms functionRaft microdomainsOncogenic RasPlasma membraneDependent regulationH-RasArf6Dependent activationDependent pathwayDownstream mediatorVital mediators
2015
KLF4 is a key determinant in the development and progression of cerebral cavernous malformations
Cuttano R, Rudini N, Bravi L, Corada M, Giampietro C, Papa E, Morini MF, Maddaluno L, Baeyens N, Adams RH, Jain MK, Owens GK, Schwartz M, Lampugnani MG, Dejana E. KLF4 is a key determinant in the development and progression of cerebral cavernous malformations. EMBO Molecular Medicine 2015, 8: 6-24. PMID: 26612856, PMCID: PMC4718159, DOI: 10.15252/emmm.201505433.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBone Morphogenetic Protein 6Cell ProliferationDisease Models, AnimalDisease ProgressionEndothelial CellsHEK293 CellsHemangioma, Cavernous, Central Nervous SystemHumansKRIT1 ProteinKruppel-Like Factor 4Kruppel-Like Transcription FactorsMiceMice, Inbred C57BLMice, KnockoutMicrotubule-Associated ProteinsMitogen-Activated Protein Kinase 7MutationProto-Oncogene ProteinsRNA InterferenceSignal TransductionSmad1 ProteinTransforming Growth Factor betaConceptsKruppel-like factor 4Cerebral cavernous malformationsEndothelial cellsCavernous malformationsFamilial cerebral cavernous malformationsCentral nervous systemDouble knockout miceGrowth factor-beta/bone morphogenetic protein signalingCerebral hemorrhageMouse mortalityPharmacological treatmentCurrent therapiesVascular malformationsKnockout miceTherapeutic targetNervous systemMesenchymal transitionKLF4 transcriptional activityMalformationsCCM3 genesFactor 4Function mutationsEndMTMorphogenetic protein signalingBone morphogenetic protein (BMP) signaling
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
2009
RalA-Exocyst Complex Regulates Integrin-Dependent Membrane Raft Exocytosis and Growth Signaling
Balasubramanian N, Meier JA, Scott DW, Norambuena A, White MA, Schwartz MA. RalA-Exocyst Complex Regulates Integrin-Dependent Membrane Raft Exocytosis and Growth Signaling. Current Biology 2009, 20: 75-79. PMID: 20005108, PMCID: PMC2822103, DOI: 10.1016/j.cub.2009.11.016.Peer-Reviewed Original ResearchConceptsPlasma membraneRecycling endosomesGrowth signalingActivation of Arf6Small GTPase RalACaveolin-dependent internalizationLipid raft microdomainsAnchorage-independent growthEffects of integrinsExocyst complexActive RalARaft microdomainsMembrane raftsRaft markersIntegrin signalingPancreatic cancer cellsRalAAnchorage dependenceAnchorage independenceCell growthSignalingCell detachmentCancer cellsEndosomesExocytosis
2007
Rac, 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 ResearchMeSH KeywordsAnimalsCaveolinsCell AdhesionCell MembraneCell ProliferationHumansIntegrinsRac GTP-Binding ProteinsConceptsCholesterol-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
Phospho-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