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  Ligand-independent degradation of epidermal growth factor receptor involves receptor ubiquitylation and hgs, an adaptor whose ubiquitin-interacting motif targets ubiquitylation by Nedd4

Katz, M., Shtiegman, K., Tal-Or, P., Yakir, L., Mosesson, Y., Harari, D., et al. (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(10), 740-751. Retrieved from http://onlinelibrary.wiley.com/doi/10.1034/j.1600-0854.2002.31006.x/pdf.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0012-F2D4-9 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0027-E43B-6
Genre: Journal Article

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 Creators:
Katz, M., Author
Shtiegman, K., Author
Tal-Or, P., Author
Yakir, L., Author
Mosesson, Y., Author
Harari, D., Author
Machluf, Y., Author
Asao, H., Author
Jovin, T. M.1, Author              
Sugamura, K., Author
Yarden, Y., Author
Affiliations:
1Department of Molecular Biology, MPI for biophysical chemistry, Max Planck Society, ou_578628              

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Free keywords: endocytosis; epidermal growth factor; Hgs/Hrs; Nedd4; signal transduction; tyrosine kinase; ubiquitin
 Abstract: 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.

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Language(s): eng - English
 Dates: 2002-10
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Method: Peer
 Degree: -

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Title: Traffic
Source Genre: Journal
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Pages: - Volume / Issue: 3 (10) Sequence Number: - Start / End Page: 740 - 751 Identifier: -