| First Author | de Melker AA | Year | 2004 |
| Journal | J Cell Sci | Volume | 117 |
| Issue | Pt 21 | Pages | 5001-12 |
| PubMed ID | 15383614 | Mgi Jnum | J:335497 |
| Mgi Id | MGI:7471043 | Doi | 10.1242/jcs.01354 |
| Citation | de Melker AA, et al. (2004) c-Cbl directs EGF receptors into an endocytic pathway that involves the ubiquitin-interacting motif of Eps15. J Cell Sci 117(Pt 21):5001-12 |
| abstractText | c-Cbl associates with the activated EGF receptor before endocytosis. We here reveal that the capacity of c-Cbl to promote receptor internalization depends on its ubiquitin ligase activity, which functionally connects the EGF receptor to Eps15, a mediator of clathrin-coated pit formation. EGF-induced phosphorylation of Eps15, as well as recruitment of Eps15 to the plasma membrane and its co-localization with the EGF receptor in endosomes required the ubiquitin ligase activity of c-Cbl. This suggested that ubiquitin provides a direct or indirect link between the receptor and Eps15. Indeed, EGF-induced redistribution of Eps15 to the plasma membrane and endosomes depended on its ubiquitin-interacting motif. Upon over-expression, the ubiquitin-interacting motif abrogated the capacity of c-Cbl to promote EGF receptor endocytosis and only allowed receptor internalization via a route that lacked Eps15. Our findings disclose a novel function for the c-Cbl ubiquitin ligase and identify ubiquitin as a module that directs the EGF receptor into an endocytic pathway involving Eps15. |
