| http://purl.uniprot.org/citations/12717443 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/12717443 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/12717443 | http://www.w3.org/2000/01/rdf-schema#comment | "The signalling cascade including Raf, mitogen-activated protein kinase (MAPK) kinase and extracellular-signal-regulated kinase (ERK) is important in many facets of cellular regulation. Raf is activated through both Ras-dependent and Ras-independent mechanisms, but the regulatory mechanisms of Raf activation remain unclear. Two families of membrane-bound molecules, Sprouty and Sprouty-related EVH1-domain-containing protein (Spred) have been identified and characterized as negative regulators of growth-factor-induced ERK activation. But the molecular functions of mammalian Sproutys have not been clarified. Here we show that mammalian Sprouty4 suppresses vascular epithelial growth factor (VEGF)-induced, Ras-independent activation of Raf1 but does not affect epidermal growth factor (EGF)-induced, Ras-dependent activation of Raf1. Sprouty4 binds to Raf1 through its carboxy-terminal cysteine-rich domain, and this binding is necessary for the inhibitory activity of Sprouty4. In addition, Sprouty4 mutants of the amino-terminal region containing the conserved tyrosine residue, which is necessary for suppressing fibroblast growth factor signalling, still inhibit the VEGF-induced ERK pathway. Our results show that receptor tyrosine kinases use distinct pathways for Raf and ERK activation and that Sprouty4 differentially regulates these pathways."xsd:string |
| http://purl.uniprot.org/citations/12717443 | http://purl.org/dc/terms/identifier | "doi:10.1038/ncb978"xsd:string |
| http://purl.uniprot.org/citations/12717443 | http://purl.org/dc/terms/identifier | "doi:10.1038/ncb978"xsd:string |
| http://purl.uniprot.org/citations/12717443 | http://purl.uniprot.org/core/author | "Sasaki M."xsd:string |
| http://purl.uniprot.org/citations/12717443 | http://purl.uniprot.org/core/author | "Sasaki M."xsd:string |
| http://purl.uniprot.org/citations/12717443 | http://purl.uniprot.org/core/author | "Saito N."xsd:string |
| http://purl.uniprot.org/citations/12717443 | http://purl.uniprot.org/core/author | "Saito N."xsd:string |
| http://purl.uniprot.org/citations/12717443 | http://purl.uniprot.org/core/author | "Sasaki A."xsd:string |
| http://purl.uniprot.org/citations/12717443 | http://purl.uniprot.org/core/author | "Sasaki A."xsd:string |
| http://purl.uniprot.org/citations/12717443 | http://purl.uniprot.org/core/author | "Kato R."xsd:string |
| http://purl.uniprot.org/citations/12717443 | http://purl.uniprot.org/core/author | "Kato R."xsd:string |
| http://purl.uniprot.org/citations/12717443 | http://purl.uniprot.org/core/author | "Saeki K."xsd:string |
| http://purl.uniprot.org/citations/12717443 | http://purl.uniprot.org/core/author | "Saeki K."xsd:string |
| http://purl.uniprot.org/citations/12717443 | http://purl.uniprot.org/core/author | "Shibuya M."xsd:string |
| http://purl.uniprot.org/citations/12717443 | http://purl.uniprot.org/core/author | "Shibuya M."xsd:string |
| http://purl.uniprot.org/citations/12717443 | http://purl.uniprot.org/core/author | "Kuriyama M."xsd:string |
| http://purl.uniprot.org/citations/12717443 | http://purl.uniprot.org/core/author | "Kuriyama M."xsd:string |
| http://purl.uniprot.org/citations/12717443 | http://purl.uniprot.org/core/author | "Yoshimura A."xsd:string |
| http://purl.uniprot.org/citations/12717443 | http://purl.uniprot.org/core/author | "Yoshimura A."xsd:string |
| http://purl.uniprot.org/citations/12717443 | http://purl.uniprot.org/core/author | "Nonami A."xsd:string |
| http://purl.uniprot.org/citations/12717443 | http://purl.uniprot.org/core/author | "Nonami A."xsd:string |
| http://purl.uniprot.org/citations/12717443 | http://purl.uniprot.org/core/author | "Taketomi T."xsd:string |
| http://purl.uniprot.org/citations/12717443 | http://purl.uniprot.org/core/author | "Taketomi T."xsd:string |