Item Type: | Article |
---|---|
Title: | Hakai, a c-Cbl-like protein, ubiquitinates and induces endocytosis of the E-cadherin complex |
Creators Name: | Fujita, Y., Krause, G., Scheffner, M., Zechner, D., Leddy, H.E.M., Behrens, J., Sommer, T. and Birchmeier, W. |
Abstract: | In epithelial cells, tyrosine kinases induce the tyrosine phosphorylation and ubiquitination of the E-cadherin complex, which induces endocytosis of E-cadherin. With a modified yeast 2-hybrid system, we isolated Hakai, an E-cadherin binding protein, which we have identified as an E3 ubiquitin-ligase. Hakai contains SH2, RING, zinc-finger and proline-rich domains, and interacts with E-cadherin in a tyrosine phosphorylation-dependent manner, inducing ubiquitination of the E-cadherin complex. Expression of Hakai in epithelial cells disrupts cell--cell contacts and enhances endocytosis of E-cadherin and cell motility. Through dynamic recycling of E-cadherin, Hakai can thus modulate cell adhesion, and could participate in the regulation of epithelial--mesenchymal transitions in development or metastasis. |
Keywords: | Amino Acid Sequence, Cadherins, Cell Adhesion, Cell Line, Cell Movement, Endocytosis, Ligases, Biological Models, Molecular Models, Molecular Sequence Data, Mutation, Protein Binding, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-cbl, Temperature, Two-Hybrid System Techniques, Ubiquitin, Ubiquitin-Protein Ligases, src-Family Kinases, Animals, Dogs |
Source: | Nature Cell Biology |
ISSN: | 1465-7392 |
Publisher: | Nature Publishing Group |
Volume: | 4 |
Number: | 3 |
Page Range: | 222-231 |
Date: | 1 March 2002 |
Official Publication: | https://doi.org/10.1038/ncb758 |
PubMed: | View item in PubMed |
Repository Staff Only: item control page