The contribution of these authors was equal.
Ligand-Independent Degradation of Epidermal Growth Factor Receptor Involves Receptor Ubiquitylation and Hgs, an Adaptor Whose Ubiquitin-Interacting Motif Targets Ubiquitylation by Nedd4
Article first published online: 16 SEP 2002
Volume 3, Issue 10, pages 740–751, October 2002
How to Cite
Katz, M., Shtiegman, K., Tal-Or, P., Yakir, L., Mosesson, Y., Harari, D., Machluf, Y., Asao, H., Jovin, T., Sugamura, K. and Yarden, Y. (2002), Ligand-Independent Degradation of Epidermal Growth Factor Receptor Involves Receptor Ubiquitylation and Hgs, an Adaptor Whose Ubiquitin-Interacting Motif Targets Ubiquitylation by Nedd4. Traffic, 3: 740–751. doi: 10.1034/j.1600-0854.2002.31006.x
- Issue published online: 16 SEP 2002
- Article first published online: 16 SEP 2002
- Received 24 September 2001,revised andaccepted for publication 9 July 2002
- epidermal growth factor;
- signal transduction;
- tyrosine kinase;
Ligand-dependent endocytosis of the epidermal growth factor receptor (EGFR) involves recruitment of a ubiquitin ligase, and sorting of ubiquitylated receptors to lysosomal degradation. By studying Hgs, a mammalian homolog of a yeast vacuolar-sorting adaptor, we provide information on the less understood, ligand-independent pathway of receptor endocytosis and degradation. Constitutive endocytosis involves receptor ubiquitylation and translocation to Hgs-containing endosomes. Whereas the lipid-binding motif of Hgs is necessary for receptor endocytosis, the ubiquitin-interacting motif negatively regulates receptor degradation. We demonstrate that the ubiquitin-interacting motif is endowed with two functions: it binds ubiquitylated proteins and it targets self-ubiquitylation by recruiting Nedd4, an ubiquitin ligase previously implicated in endocytosis. Based upon the dual function of the ubiquitin-interacting motif and its wide occurrence in endocytic adaptors, we propose a ubiquitin-interacting motif network that relays ubiquitylated membrane receptors to lysosomal degradation through successive budding events.