JNK regulates binding of α-catenin to adherens junctions and cell-cell adhesion

We recently reported that c-Jun N-terminal kinase (JNK) is associated with adherens junctions and phosphorylates beta-catenin at serine 33/37 and threonine 41. Here, we report that inhibition of JNK led to formation of adherens junctions, which was accompanied by dissociation of alpha-catenin from the beta-catenin/E-cadherin complex and increased association of alpha-catenin with the cytoskeleton. Conversely, activation of JNK increased binding of alpha-catenin to beta-catenin, which was blocked by the JNK inhibitor SP600125 or JNK siRNA. In addition, inhibition of JNK failed to lead to adherens junction formation in cells where alpha-catenin was absent or knocked down. Conversely, introduction of alpha-catenin restored the responsiveness of cells to JNK inhibition and led to cell-cell adhesion. Experiments with domain deletion mutants showed that binding of alpha-catenin to beta-catenin was required for transport of adherens junction complexes to the cell surface, while binding to actin was required for translocation to the cell-cell contact sites. Collectively, our results suggest that JNK affects the association of alpha-catenin with the adherens junction complex and regulates adherens junctions.-Lee, M.-H., Padmashali, R., Koria, P., Andreadis, S. T. JNK regulates binding of alpha-catenin to adherens junctions and cell-cell adhesion. FASEB J. 25, 613-623 (2011). www.fasebj.org