| http://purl.uniprot.org/citations/21636859 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/21636859 | http://www.w3.org/2000/01/rdf-schema#comment | "Vascular endothelial growth factor (VEGF) acting through VEGF receptor 2 (VEGFR2) on endothelial cells (ECs) is a key regulator of angiogenesis, a process essential for wound healing and tumor metastasis. Rap1a and Rap1b, 2 highly homologous small G proteins, are both required for angiogenesis in vivo and for normal EC responses to VEGF. Here we sought to determine the mechanism through which Rap1 promotes VEGF-mediated angiogenesis. Using lineage-restricted Rap1-knockout mice we show that Rap1-deficiency in endothelium leads to defective angiogenesis in vivo, in a dose-dependent manner. Using ECs obtained from Rap1-deficient mice we demonstrate that Rap1b promotes VEGF-VEGFR2 kinase activation and regulates integrin activation. Importantly, the Rap1b-dependent VEGF-VEGFR2 activation is in part mediated via integrin α(v)β(3). Furthermore, in an in vivo model of zebrafish angiogenesis, we demonstrate that Rap1b is essential for the sprouting of intersomitic vessels, a process known to be dependent on VEGF signaling. Using 2 distinct pharmacologic VEGFR2 inhibitors we show that Rap1b and VEGFR2 act additively to control angiogenesis in vivo. We conclude that Rap1b promotes VEGF-mediated angiogenesis by promoting VEGFR2 activation in ECs via integrin α(v)β(3). These results provide a novel insight into the role of Rap1 in VEGF signaling in ECs."xsd:string |
| http://purl.uniprot.org/citations/21636859 | http://purl.org/dc/terms/identifier | "doi:10.1182/blood-2011-04-349282"xsd:string |
| http://purl.uniprot.org/citations/21636859 | http://purl.uniprot.org/core/author | "Ramchandran R."xsd:string |
| http://purl.uniprot.org/citations/21636859 | http://purl.uniprot.org/core/author | "Sobczak M."xsd:string |
| http://purl.uniprot.org/citations/21636859 | http://purl.uniprot.org/core/author | "Chun C."xsd:string |
| http://purl.uniprot.org/citations/21636859 | http://purl.uniprot.org/core/author | "Henschel A."xsd:string |
| http://purl.uniprot.org/citations/21636859 | http://purl.uniprot.org/core/author | "Chrzanowska-Wodnicka M."xsd:string |
| http://purl.uniprot.org/citations/21636859 | http://purl.uniprot.org/core/author | "Dargatz J."xsd:string |
| http://purl.uniprot.org/citations/21636859 | http://purl.uniprot.org/core/author | "Lakshmikanthan S."xsd:string |
| http://purl.uniprot.org/citations/21636859 | http://purl.uniprot.org/core/date | "2011"xsd:gYear |
| http://purl.uniprot.org/citations/21636859 | http://purl.uniprot.org/core/name | "Blood"xsd:string |
| http://purl.uniprot.org/citations/21636859 | http://purl.uniprot.org/core/pages | "2015-2026"xsd:string |
| http://purl.uniprot.org/citations/21636859 | http://purl.uniprot.org/core/title | "Rap1 promotes VEGFR2 activation and angiogenesis by a mechanism involving integrin alphavbeta(3)."xsd:string |
| http://purl.uniprot.org/citations/21636859 | http://purl.uniprot.org/core/volume | "118"xsd:string |
| http://purl.uniprot.org/citations/21636859 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/21636859 |
| http://purl.uniprot.org/citations/21636859 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/21636859 |
| http://purl.uniprot.org/uniprot/#_A0A0G2JDL9-mappedCitation-21636859 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/21636859 |
| http://purl.uniprot.org/uniprot/#_A0A0F7IQ06-mappedCitation-21636859 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/21636859 |
| http://purl.uniprot.org/uniprot/#_A0A0G2JE52-mappedCitation-21636859 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/21636859 |
| http://purl.uniprot.org/uniprot/#_A0A0G2JED9-mappedCitation-21636859 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/21636859 |
| http://purl.uniprot.org/uniprot/#_A2AKI5-mappedCitation-21636859 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/21636859 |
| http://purl.uniprot.org/uniprot/#_A0A1W2P777-mappedCitation-21636859 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/21636859 |
| http://purl.uniprot.org/uniprot/#_B7ZCI9-mappedCitation-21636859 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/21636859 |
| http://purl.uniprot.org/uniprot/#_C5H0E9-mappedCitation-21636859 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/21636859 |