Home News About Us Contact Contributors Disclaimer Privacy Policy Help FAQ

Quick Search
My eDoc
Session History
Support Wiki
Direct access to
document ID:

          Institute: MPI für biophysikalische Chemie     Collection: Molekulare Biologie (Dr. Thomas M. Jovin)     Display Documents

ID: 16659.0, MPI für biophysikalische Chemie / Molekulare Biologie (Dr. Thomas M. Jovin)
Ligand-independent degradation of epidermal growth factor receptor involves receptor ubiquitylation and hgs, an adaptor whose ubiquitin-interacting motif targets ubiquitylation by Nedd4
Authors:Katz, M.; Shtiegman, K.; Tal-Or, P.; Yakir, L.; Mosesson, Y.; Harari, D.; Machluf, Y.; Asao, H.; Jovin, T. M.; Sugamura, K.; Yarden, Y.
Date of Publication (YYYY-MM-DD):2002-10
Title of Journal:Traffic
Issue / Number:10
Start Page:740
End Page:751
Review Status:Peer-review
Audience:Not Specified
Abstract / Description: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.
Free Keywords:endocytosis; epidermal growth factor; Hgs/Hrs; Nedd4; signal transduction; tyrosine kinase; ubiquitin
Comment of the Author/Creator:Date: 2002, OCT
External Publication Status:published
Document Type:Article
Communicated by:N. N.
Affiliations:MPI für biophysikalische Chemie/Abt. Thomas Jovin / 060
External Affiliations:Weizmann Inst Sci, Dept Regulat Biol, IL-76100 Rehovot, Israel; Weizmann Inst Sci, Dept Regulat Biol, IL-76100 Rehovot, Israel; Tohoku Univ, Sch Med, Dept Microbiol & Immunol, Sendai, Miyagi 98077, Japan
The scope and number of records on eDoc is subject to the collection policies defined by each institute - see "info" button in the collection browse view.