Hakai, a c-Cbl-like protein, ubiquitinates and induces endocytosis of the E-cadherin complex.
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.
Mesh Terms:
Amino Acid Sequence, Animals, Cadherins, Cell Adhesion, Cell Line, Cell Movement, Dogs, Endocytosis, Ligases, Models, Biological, Models, Molecular, 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
Amino Acid Sequence, Animals, Cadherins, Cell Adhesion, Cell Line, Cell Movement, Dogs, Endocytosis, Ligases, Models, Biological, Models, Molecular, 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
Nat. Cell Biol.
Date: Mar. 01, 2002
PubMed ID: 11836526
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