| http://purl.uniprot.org/citations/19710505 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/19710505 | http://www.w3.org/2000/01/rdf-schema#comment | "Tumors depend upon angiogenesis for growth and metastasis. It is therefore critical to understand the inhibitory signaling mechanisms in endothelial cells that control angiogenesis. Epac is a cyclic adenosine 5'-monophosphate-activated guanine nucleotide exchange factor for Rap1. In this study, we show that activation of Epac or Rap1 leads to potent inhibition of angiogenesis in vivo. Epac/Rap1 activation down-regulates inhibitor of differentiation 1 (Id1), which negatively regulates thrombospondin-1 (TSP1), an inhibitor of angiogenesis. Consistent with this mechanism, activation of Epac/Rap 1 induces expression of TSP1; conversely, depletion of Epac reduces TSP1 levels in endothelial cells. Blockade of TSP1 binding to its receptor, CD36, rescues inhibition of chemotaxis or angiogenesis by activated Epac/Rap1. Mitogen-activated protein kinase kinase 5, a downstream mediator of vascular endothelial growth factor, antagonizes the effects of Epac/Rap1 by inducing Id1 and suppressing TSP1 expression. Finally, TSP1 is also secreted by fibroblasts in response to Epac/Rap1 activation. These results identify Epac and Rap1 as inhibitory regulators of the angiogenic process, implicate Id1 and TSP1 as downstream mediators of Epac/Rap1, and highlight a novel interplay between pro- and antiangiogenic signaling cascades involving multiple cell types within the angiogenic microenvironment."xsd:string |
| http://purl.uniprot.org/citations/19710505 | http://purl.org/dc/terms/identifier | "doi:10.1182/blood-2009-04-217042"xsd:string |
| http://purl.uniprot.org/citations/19710505 | http://purl.uniprot.org/core/author | "Liu Y."xsd:string |
| http://purl.uniprot.org/citations/19710505 | http://purl.uniprot.org/core/author | "Hong J."xsd:string |
| http://purl.uniprot.org/citations/19710505 | http://purl.uniprot.org/core/author | "Rosner M.R."xsd:string |
| http://purl.uniprot.org/citations/19710505 | http://purl.uniprot.org/core/author | "Gomes S."xsd:string |
| http://purl.uniprot.org/citations/19710505 | http://purl.uniprot.org/core/author | "Abe M.K."xsd:string |
| http://purl.uniprot.org/citations/19710505 | http://purl.uniprot.org/core/author | "Doebele R.C."xsd:string |
| http://purl.uniprot.org/citations/19710505 | http://purl.uniprot.org/core/author | "Chlenski A."xsd:string |
| http://purl.uniprot.org/citations/19710505 | http://purl.uniprot.org/core/author | "Lingen M.W."xsd:string |
| http://purl.uniprot.org/citations/19710505 | http://purl.uniprot.org/core/author | "Nor J.E."xsd:string |
| http://purl.uniprot.org/citations/19710505 | http://purl.uniprot.org/core/author | "Zeitlin B.D."xsd:string |
| http://purl.uniprot.org/citations/19710505 | http://purl.uniprot.org/core/author | "Goel K."xsd:string |
| http://purl.uniprot.org/citations/19710505 | http://purl.uniprot.org/core/author | "Schulze-Hoepfner F.T."xsd:string |
| http://purl.uniprot.org/citations/19710505 | http://purl.uniprot.org/core/date | "2009"xsd:gYear |
| http://purl.uniprot.org/citations/19710505 | http://purl.uniprot.org/core/name | "Blood"xsd:string |
| http://purl.uniprot.org/citations/19710505 | http://purl.uniprot.org/core/pages | "4592-4600"xsd:string |
| http://purl.uniprot.org/citations/19710505 | http://purl.uniprot.org/core/title | "A novel interplay between Epac/Rap1 and mitogen-activated protein kinase kinase 5/extracellular signal-regulated kinase 5 (MEK5/ERK5) regulates thrombospondin to control angiogenesis."xsd:string |
| http://purl.uniprot.org/citations/19710505 | http://purl.uniprot.org/core/volume | "114"xsd:string |
| http://purl.uniprot.org/citations/19710505 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/19710505 |
| http://purl.uniprot.org/citations/19710505 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/19710505 |
| http://purl.uniprot.org/uniprot/#_A0A0B6XK25-mappedCitation-19710505 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/19710505 |
| http://purl.uniprot.org/uniprot/#_A0PJG0-mappedCitation-19710505 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/19710505 |
| http://purl.uniprot.org/uniprot/#_A8KAH9-mappedCitation-19710505 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/19710505 |