| http://purl.uniprot.org/citations/21765395 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/21765395 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/21765395 | http://www.w3.org/2000/01/rdf-schema#comment | "Fibroblast growth factor receptor 1 (FGFR1) has critical roles in cellular proliferation and differentiation during animal development and adult homeostasis. Here, we show that human Nedd4 (Nedd4-1), an E3 ubiquitin ligase comprised of a C2 domain, 4 WW domains, and a Hect domain, regulates endocytosis and signalling of FGFR1. Nedd4-1 binds directly to and ubiquitylates activated FGFR1, by interacting primarily via its WW3 domain with a novel non-canonical sequence (non-PY motif) on FGFR1. Deletion of this recognition motif (FGFR1-Δ6) abolishes Nedd4-1 binding and receptor ubiquitylation, and impairs endocytosis of activated receptor, as also observed upon Nedd4-1 knockdown. Accordingly, FGFR1-Δ6, or Nedd4-1 knockdown, exhibits sustained FGF-dependent receptor Tyr phosphorylation and downstream signalling (activation of FRS2α, Akt, Erk1/2, and PLCγ). Expression of FGFR1-Δ6 in human embryonic neural stem cells strongly promotes FGF2-dependent neuronal differentiation. Furthermore, expression of this FGFR1-Δ6 mutant in zebrafish embryos disrupts anterior neuronal patterning (head development), consistent with excessive FGFR1 signalling. These results identify Nedd4-1 as a key regulator of FGFR1 endocytosis and signalling during neuronal differentiation and embryonic development."xsd:string |
| http://purl.uniprot.org/citations/21765395 | http://purl.org/dc/terms/identifier | "doi:10.1038/emboj.2011.234"xsd:string |
| http://purl.uniprot.org/citations/21765395 | http://purl.org/dc/terms/identifier | "doi:10.1038/emboj.2011.234"xsd:string |
| http://purl.uniprot.org/citations/21765395 | http://purl.uniprot.org/core/author | "Sicheri F."xsd:string |
| http://purl.uniprot.org/citations/21765395 | http://purl.uniprot.org/core/author | "Sicheri F."xsd:string |
| http://purl.uniprot.org/citations/21765395 | http://purl.uniprot.org/core/author | "Persaud A."xsd:string |
| http://purl.uniprot.org/citations/21765395 | http://purl.uniprot.org/core/author | "Persaud A."xsd:string |
| http://purl.uniprot.org/citations/21765395 | http://purl.uniprot.org/core/author | "Rotin D."xsd:string |
| http://purl.uniprot.org/citations/21765395 | http://purl.uniprot.org/core/author | "Rotin D."xsd:string |
| http://purl.uniprot.org/citations/21765395 | http://purl.uniprot.org/core/author | "Hayes M."xsd:string |
| http://purl.uniprot.org/citations/21765395 | http://purl.uniprot.org/core/author | "Hayes M."xsd:string |
| http://purl.uniprot.org/citations/21765395 | http://purl.uniprot.org/core/author | "Alberts P."xsd:string |
| http://purl.uniprot.org/citations/21765395 | http://purl.uniprot.org/core/author | "Alberts P."xsd:string |
| http://purl.uniprot.org/citations/21765395 | http://purl.uniprot.org/core/author | "Dirks P."xsd:string |
| http://purl.uniprot.org/citations/21765395 | http://purl.uniprot.org/core/author | "Dirks P."xsd:string |
| http://purl.uniprot.org/citations/21765395 | http://purl.uniprot.org/core/author | "Ciruna B."xsd:string |
| http://purl.uniprot.org/citations/21765395 | http://purl.uniprot.org/core/author | "Ciruna B."xsd:string |
| http://purl.uniprot.org/citations/21765395 | http://purl.uniprot.org/core/author | "Clarke I."xsd:string |
| http://purl.uniprot.org/citations/21765395 | http://purl.uniprot.org/core/author | "Clarke I."xsd:string |
| http://purl.uniprot.org/citations/21765395 | http://purl.uniprot.org/core/author | "Guettler S."xsd:string |
| http://purl.uniprot.org/citations/21765395 | http://purl.uniprot.org/core/author | "Guettler S."xsd:string |
| http://purl.uniprot.org/citations/21765395 | http://purl.uniprot.org/core/date | "2011"xsd:gYear |
| http://purl.uniprot.org/citations/21765395 | http://purl.uniprot.org/core/date | "2011"xsd:gYear |