RDF/XMLNTriplesTurtleShow queryShare
SubjectPredicateObject
http://purl.uniprot.org/citations/24522833http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/24522833http://www.w3.org/2000/01/rdf-schema#comment"β1-Integrins are essential for angiogenesis. The mechanisms regulating integrin function in endothelial cells (EC) and their contribution to angiogenesis remain elusive. Brag2 is a guanine nucleotide exchange factor for the small Arf-GTPases Arf5 and Arf6. The role of Brag2 in EC and angiogenesis and the underlying molecular mechanisms remain unclear. siRNA-mediated Brag2-silencing reduced EC angiogenic sprouting and migration. Brag2-siRNA transfection differentially affected α5β1- and αVβ3-integrin function: specifically, Brag2-silencing increased focal/fibrillar adhesions and adhesion on β1-integrin ligands (fibronectin and collagen), while reducing the adhesion on the αVβ3-integrin ligand, vitronectin. Consistent with these results, Brag2-silencing enhanced surface expression of α5β1-integrin, while reducing surface expression of αVβ3-integrin. Mechanistically, Brag2-mediated αVβ3-integrin-recycling and β1-integrin endocytosis and specifically of the active/matrix-bound α5β1-integrin present in fibrillar/focal adhesions (FA), suggesting that Brag2 contributes to the disassembly of FA via β1-integrin endocytosis. Arf5 and Arf6 are promoting downstream of Brag2 angiogenic sprouting, β1-integrin endocytosis and the regulation of FA. In vivo silencing of the Brag2-orthologues in zebrafish embryos using morpholinos perturbed vascular development. Furthermore, in vivo intravitreal injection of plasmids containing Brag2-shRNA reduced pathological ischemia-induced retinal and choroidal neovascularization. These data reveal that Brag2 is essential for developmental and pathological angiogenesis by promoting EC sprouting through regulation of adhesion by mediating β1-integrin internalization and link for the first time the process of β1-integrin endocytosis with angiogenesis."xsd:string
http://purl.uniprot.org/citations/24522833http://purl.org/dc/terms/identifier"doi:10.1007/s00395-014-0404-2"xsd:string
http://purl.uniprot.org/citations/24522833http://purl.uniprot.org/core/author"Li X."xsd:string
http://purl.uniprot.org/citations/24522833http://purl.uniprot.org/core/author"Tang Z."xsd:string
http://purl.uniprot.org/citations/24522833http://purl.uniprot.org/core/author"Zhang F."xsd:string
http://purl.uniprot.org/citations/24522833http://purl.uniprot.org/core/author"Sakurai A."xsd:string
http://purl.uniprot.org/citations/24522833http://purl.uniprot.org/core/author"Gutkind J.S."xsd:string
http://purl.uniprot.org/citations/24522833http://purl.uniprot.org/core/author"Dimmeler S."xsd:string
http://purl.uniprot.org/citations/24522833http://purl.uniprot.org/core/author"Zeiher A.M."xsd:string
http://purl.uniprot.org/citations/24522833http://purl.uniprot.org/core/author"Chavakis E."xsd:string
http://purl.uniprot.org/citations/24522833http://purl.uniprot.org/core/author"Kroll J."xsd:string
http://purl.uniprot.org/citations/24522833http://purl.uniprot.org/core/author"Carmona G."xsd:string
http://purl.uniprot.org/citations/24522833http://purl.uniprot.org/core/author"Bennewitz K."xsd:string
http://purl.uniprot.org/citations/24522833http://purl.uniprot.org/core/author"Manavski Y."xsd:string
http://purl.uniprot.org/citations/24522833http://purl.uniprot.org/core/date"2014"xsd:gYear
http://purl.uniprot.org/citations/24522833http://purl.uniprot.org/core/name"Basic Res Cardiol"xsd:string
http://purl.uniprot.org/citations/24522833http://purl.uniprot.org/core/pages"404"xsd:string
http://purl.uniprot.org/citations/24522833http://purl.uniprot.org/core/title"Brag2 differentially regulates beta1- and beta3-integrin-dependent adhesion in endothelial cells and is involved in developmental and pathological angiogenesis."xsd:string
http://purl.uniprot.org/citations/24522833http://purl.uniprot.org/core/volume"109"xsd:string
http://purl.uniprot.org/citations/24522833http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/24522833
http://purl.uniprot.org/citations/24522833http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/24522833
http://purl.uniprot.org/uniprot/A0A8M2BGL9#attribution-079088DB246B76CA19F63385478A4AE5http://purl.uniprot.org/core/sourcehttp://purl.uniprot.org/citations/24522833
http://purl.uniprot.org/uniprot/A0A8M2BGL9#attribution-37CBE55CA3806477C4C1F0ABF6066DC6http://purl.uniprot.org/core/sourcehttp://purl.uniprot.org/citations/24522833
http://purl.uniprot.org/uniprot/A0A8M2BGL8#attribution-079088DB246B76CA19F63385478A4AE5http://purl.uniprot.org/core/sourcehttp://purl.uniprot.org/citations/24522833