JNK phosphorylates beta-catenin and regulates adherens junctions.

The c-Jun amino-terminal kinase (JNK) is an important player in inflammation, proliferation, and apoptosis. More recently, JNK was found to regulate cell migration by phosphorylating paxillin. Here, we report a novel role of JNK in cell adhesion. Specifically, we provide evidence that JNK binds to E-cadherin/beta-catenin complex and phosphorylates beta-catenin at serine 37 and threonine 41, the sites also phosphorylated by GSK-3beta. Inhibition of JNK kinase activity using dominant-negative constructs reduces phosphorylation of beta-catenin and promotes localization of E-cadherin/beta-catenin complex to cell-cell contact sites. Conversely, activation of JNK induces beta-catenin phosphorylation and disruption of cell contacts, which are prevented by JNK siRNA. We propose that JNK binds to beta-catenin and regulates formation of adherens junctions, ultimately controlling cell-to-cell adhesion.