(86c) JNK-Mediated Regulation of Cell-Cell Adhesion

Cell-cell adhesion is dynamically regulated under different biological circumstances such as the establishment of epithelial cell polarity, wound healing, cell scattering and tumorigenesis. However, the mechanism of adherens junction regulation is not completely understood. The current work led to the discovery that c-Jun N-terminal kinase (JNK) is associated with adherens junctions and regulates cell-cell adhesion. Specifically, we indentified that JNK phosphorylated beta-catenin at serine 33/37 and threonine 41. Blocking JNK led to the release of alpha-catenin from the adherens junction complex and promoted translocation of E-cadherin and beta-catenin to the cell-cell contact sites and formation of compact colonies. In addition, the domains of alpha-catenin that are necessary for these interactions have been identified by expressing several alpha-catenin mutants in epithelial cells lacking alpha-catenin and monitoring adherens junction formation using confocal microscopy. Our results suggest that JNK acts as a switch that regulates adherens junctions by controlling binding of alpha-catenin to beta-catenin. These finding may have wide implications in understanding the process of cell-cell communication, formation of epithelial tissues and cancer metastasis.