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.
Pubmed ID: 11836526 RIS Download
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