| http://purl.uniprot.org/citations/20086093 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/20086093 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/20086093 | http://www.w3.org/2000/01/rdf-schema#comment | "ACK (activated Cdc42-associated tyrosine kinase) (also Tnk2) is an ubiquitin-binding protein and plays an important role in ligand-induced and ubiquitination-mediated degradation of epidermal growth factor receptor (EGFR). Here we report that ACK is ubiquitinated by HECT E3 ubiquitin ligase Nedd4-1 and degraded along with EGFR in response to EGF stimulation. ACK interacts with Nedd4-1 through a conserved PPXY WW-binding motif. The WW3 domain in Nedd4-1 is critical for binding to ACK. Although ACK binds to both Nedd4-1 and Nedd4-2 (also Nedd4L), Nedd4-1 is the E3 ubiquitin ligase for ubiquitination of ACK in cells. Interestingly, deletion of the sterile alpha motif (SAM) domain at the N terminus dramatically reduced the ubiquitination of ACK by Nedd4-1, while deletion of the Uba domain dramatically enhanced the ubiquitination. Use of proteasomal and lysosomal inhibitors demonstrated that EGF-induced ACK degradation is processed by lysosomes, not proteasomes. RNA interference (RNAi) knockdown of Nedd4-1, not Nedd4-2, inhibited degradation of both EGFR and ACK, and overexpression of ACK mutants that are deficient in either binding to or ubiquitination by Nedd4-1 blocked EGF-induced degradation of EGFR. Our findings suggest an essential role of Nedd4-1 in regulation of EGFR degradation through interaction with and ubiquitination of ACK."xsd:string |
| http://purl.uniprot.org/citations/20086093 | http://purl.org/dc/terms/identifier | "doi:10.1128/mcb.00013-10"xsd:string |
| http://purl.uniprot.org/citations/20086093 | http://purl.org/dc/terms/identifier | "doi:10.1128/mcb.00013-10"xsd:string |
| http://purl.uniprot.org/citations/20086093 | http://purl.uniprot.org/core/author | "Lin Q."xsd:string |
| http://purl.uniprot.org/citations/20086093 | http://purl.uniprot.org/core/author | "Lin Q."xsd:string |
| http://purl.uniprot.org/citations/20086093 | http://purl.uniprot.org/core/author | "Wang J."xsd:string |
| http://purl.uniprot.org/citations/20086093 | http://purl.uniprot.org/core/author | "Wang J."xsd:string |
| http://purl.uniprot.org/citations/20086093 | http://purl.uniprot.org/core/author | "Yang W."xsd:string |
| http://purl.uniprot.org/citations/20086093 | http://purl.uniprot.org/core/author | "Yang W."xsd:string |
| http://purl.uniprot.org/citations/20086093 | http://purl.uniprot.org/core/author | "Sudol M."xsd:string |
| http://purl.uniprot.org/citations/20086093 | http://purl.uniprot.org/core/author | "Sudol M."xsd:string |
| http://purl.uniprot.org/citations/20086093 | http://purl.uniprot.org/core/author | "Carey D.J."xsd:string |
| http://purl.uniprot.org/citations/20086093 | http://purl.uniprot.org/core/author | "Carey D.J."xsd:string |
| http://purl.uniprot.org/citations/20086093 | http://purl.uniprot.org/core/author | "Childress C."xsd:string |
| http://purl.uniprot.org/citations/20086093 | http://purl.uniprot.org/core/author | "Childress C."xsd:string |
| http://purl.uniprot.org/citations/20086093 | http://purl.uniprot.org/core/date | "2010"xsd:gYear |
| http://purl.uniprot.org/citations/20086093 | http://purl.uniprot.org/core/date | "2010"xsd:gYear |
| http://purl.uniprot.org/citations/20086093 | http://purl.uniprot.org/core/name | "Mol. Cell. Biol."xsd:string |
| http://purl.uniprot.org/citations/20086093 | http://purl.uniprot.org/core/name | "Mol. Cell. Biol."xsd:string |
| http://purl.uniprot.org/citations/20086093 | http://purl.uniprot.org/core/pages | "1541-1554"xsd:string |
| http://purl.uniprot.org/citations/20086093 | http://purl.uniprot.org/core/pages | "1541-1554"xsd:string |
| http://purl.uniprot.org/citations/20086093 | http://purl.uniprot.org/core/title | "HECT E3 ubiquitin ligase Nedd4-1 ubiquitinates ACK and regulates epidermal growth factor (EGF)-induced degradation of EGF receptor and ACK."xsd:string |
| http://purl.uniprot.org/citations/20086093 | http://purl.uniprot.org/core/title | "HECT E3 ubiquitin ligase Nedd4-1 ubiquitinates ACK and regulates epidermal growth factor (EGF)-induced degradation of EGF receptor and ACK."xsd:string |