| http://purl.uniprot.org/citations/20525694 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/20525694 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/20525694 | http://www.w3.org/2000/01/rdf-schema#comment | "Cbl proteins are ubiquitin ligases (E3s) that play a significant role in regulating tyrosine kinase signaling. There are three mammalian family members: Cbl, Cbl-b, and Cbl-c. All have a highly conserved N-terminal tyrosine kinase binding domain, a catalytic RING finger domain, and a C-terminal proline-rich domain that mediates interactions with Src homology 3 (SH3) containing proteins. Although both Cbl and Cbl-b have been studied widely, little is known about Cbl-c. Published reports have demonstrated that the N terminus of Cbl and Cbl-b have an inhibitory effect on their respective E3 activity. However, the mechanism for this inhibition is still unknown. In this study we demonstrate that the N terminus of Cbl-c, like that of Cbl and Cbl-b, inhibits the E3 activity of Cbl-c. Furthermore, we map the region responsible for the inhibition to the EF-hand and SH2 domains. Phosphorylation of a critical tyrosine (Tyr-341) in the linker region of Cbl-c by Src or a phosphomimetic mutation of this tyrosine (Y341E) is sufficient to increase the E3 activity of Cbl-c. We also demonstrate for the first time that phosphorylation of Tyr-341 or the Y341E mutation leads to a decrease in affinity for the ubiquitin-conjugating enzyme (E2), UbcH5b. The decreased affinity of the Y341E mutant Cbl-c for UbcH5b results in a more rapid turnover of bound UbcH5b coincident with the increased E3 activity. These data suggest that the N terminus of Cbl-c contributes to the binding to the E2 and that phosphorylation of Tyr-341 leads to a decrease in affinity and an increase in the E3 activity of Cbl-c."xsd:string |
| http://purl.uniprot.org/citations/20525694 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m109.091157"xsd:string |
| http://purl.uniprot.org/citations/20525694 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m109.091157"xsd:string |
| http://purl.uniprot.org/citations/20525694 | http://purl.uniprot.org/core/author | "Lipkowitz S."xsd:string |
| http://purl.uniprot.org/citations/20525694 | http://purl.uniprot.org/core/author | "Lipkowitz S."xsd:string |
| http://purl.uniprot.org/citations/20525694 | http://purl.uniprot.org/core/author | "Nau M.M."xsd:string |
| http://purl.uniprot.org/citations/20525694 | http://purl.uniprot.org/core/author | "Nau M.M."xsd:string |
| http://purl.uniprot.org/citations/20525694 | http://purl.uniprot.org/core/author | "Nicholas S."xsd:string |
| http://purl.uniprot.org/citations/20525694 | http://purl.uniprot.org/core/author | "Nicholas S."xsd:string |
| http://purl.uniprot.org/citations/20525694 | http://purl.uniprot.org/core/author | "Ryan P.E."xsd:string |
| http://purl.uniprot.org/citations/20525694 | http://purl.uniprot.org/core/author | "Ryan P.E."xsd:string |
| http://purl.uniprot.org/citations/20525694 | http://purl.uniprot.org/core/author | "Sivadasan-Nair N."xsd:string |
| http://purl.uniprot.org/citations/20525694 | http://purl.uniprot.org/core/author | "Sivadasan-Nair N."xsd:string |
| http://purl.uniprot.org/citations/20525694 | http://purl.uniprot.org/core/date | "2010"xsd:gYear |
| http://purl.uniprot.org/citations/20525694 | http://purl.uniprot.org/core/date | "2010"xsd:gYear |
| http://purl.uniprot.org/citations/20525694 | http://purl.uniprot.org/core/name | "J. Biol. Chem."xsd:string |
| http://purl.uniprot.org/citations/20525694 | http://purl.uniprot.org/core/name | "J. Biol. Chem."xsd:string |
| http://purl.uniprot.org/citations/20525694 | http://purl.uniprot.org/core/pages | "23687-23698"xsd:string |
| http://purl.uniprot.org/citations/20525694 | http://purl.uniprot.org/core/pages | "23687-23698"xsd:string |
| http://purl.uniprot.org/citations/20525694 | http://purl.uniprot.org/core/title | "The N terminus of Cbl-c regulates ubiquitin ligase activity by modulating affinity for the ubiquitin-conjugating enzyme."xsd:string |
| http://purl.uniprot.org/citations/20525694 | http://purl.uniprot.org/core/title | "The N terminus of Cbl-c regulates ubiquitin ligase activity by modulating affinity for the ubiquitin-conjugating enzyme."xsd:string |
| http://purl.uniprot.org/citations/20525694 | http://purl.uniprot.org/core/volume | "285"xsd:string |
| http://purl.uniprot.org/citations/20525694 | http://purl.uniprot.org/core/volume | "285"xsd:string |