Conjugation to Nedd8 Instigates Ubiquitylation and Down-regulation of Activated Receptor Tyrosine Kinases.
From: Department of Biological Regulation, The Weizmann Institute of Science, Rehovot 76100, Israel.
The Journal of biological chemistry
- Publish Date: Aug 2006
- ISSN: 0021-9258
- Volume: 281
- Issue: 31
- Pages: 21640-51
- Medium: Print
- Language: English
- Citation (JAMA): Oved Shlomo, Mosesson Yaron, Zwang Yaara, et al. Conjugation to Nedd8 Instigates Ubiquitylation and Down-regulation of Activated Receptor Tyrosine Kinases.. J. Biol. Chem. Aug 2006;281:21640-51
Abstract
When appended to the epidermal growth factor receptor (EGFR), ubiquitin serves as a sorting signal for lysosomal degradation. Here we demonstrate that the ubiquitin ligase of EGFR, namely c-Cbl, also mediates receptor modification with the ubiquitin-like molecule Nedd8. EGF stimulates receptor neddylation, which enhances subsequent ubiquitylation, as well as sorting of EGFR for degradation. Multiple lysine residues, located within the tyrosine kinase domain of EGFR, serve as attachment sites for Nedd8. A set of clathrin coat-associated binders of ubiquitin also bind Nedd8, but they undergo ubiquitylation, not neddylation. We discuss the emerging versatility of the concerted action of ubiquitylation and neddylation in the process that desensitizes growth factor-activated receptor tyrosine kinases.
Mesh Headings (Keywords): Animals, Binding Sites, CHO Cells, Cricetinae, Down-Regulation, Hela Cells, Humans, Lysosomes, Protein Transport, Proto-Oncogene Proteins c-cbl, Receptor Protein-Tyrosine Kinases, Receptor, Epidermal Growth Factor, Ubiquitin-Protein Ligases, Ubiquitins
Check for Full Text / PubMed Unique Identifier (PMID): 16735510
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