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Hakai, a c-Cbl-like protein, ubiquitinates and induces endocytosis of the E-cadherin complex

Item Type:Article
Title:Hakai, a c-Cbl-like protein, ubiquitinates and induces endocytosis of the E-cadherin complex
Creators Name:Fujita, Y. and Krause, G. and Scheffner, M. and Zechner, D. and Leddy, H.E.M. and Behrens, J. and 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
Publisher:Nature Publishing Group
Page Range:222-231
Date:1 March 2002
Official Publication:https://doi.org/10.1038/ncb758
PubMed:View item in PubMed

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