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- Title
Hakai, a c-Cbl-like protein, ubiquitinates and induces endocytosis of the E-cadherin complex.
- Authors
Fujita, Yasuyuki; Krause, Gerd; Scheffner, Martin; Zechner, Dietmar; Leddy, Hugo E Molina; Behrens, Jürgen; Sommer, Thomas; Birchmeier, Walter
- 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.
- Publication
Nature cell biology, 2002, Vol 4, Issue 3, p222
- ISSN
1465-7392
- Publication type
Journal Article
- DOI
10.1038/ncb758