Bioengineering Laboratory, Department of Chemical and Biological Engineering, University at Buffalo, State University of New York, Amherst, NY 14260-4200, USA.
FASEB J. 2011 Feb;25(2):613-23. doi: 10.1096/fj.10-161380. Epub 2010 Oct 28.
We recently reported that c-Jun N-terminal kinase (JNK) is associated with adherens junctions and phosphorylates β-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 α-catenin from the β-catenin/E-cadherin complex and increased association of α-catenin with the cytoskeleton. Conversely, activation of JNK increased binding of α-catenin to β-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 α-catenin was absent or knocked down. Conversely, introduction of α-catenin restored the responsiveness of cells to JNK inhibition and led to cell-cell adhesion. Experiments with domain deletion mutants showed that binding of α-catenin to β-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 α-catenin with the adherens junction complex and regulates adherens junctions.
我们最近报道称，c-Jun N-末端激酶（JNK）与黏着连接有关，并使β-连环蛋白在丝氨酸 33/37 和苏氨酸 41 位发生磷酸化。在这里，我们报告称，JNK 的抑制导致黏着连接的形成，这伴随着α-连环蛋白从β-连环蛋白/E-钙黏蛋白复合物的解离以及α-连环蛋白与细胞骨架的增加关联。相反，JNK 的激活增加了α-连环蛋白与β-连环蛋白的结合，而 JNK 抑制剂 SP600125 或 JNK siRNA 可阻断这种结合。此外，在α-连环蛋白缺失或敲低的细胞中，JNK 的抑制不能导致黏着连接的形成。相反，α-连环蛋白的引入恢复了细胞对 JNK 抑制的反应性，并导致细胞间的粘附。结构域缺失突变体的实验表明，α-连环蛋白与β-连环蛋白的结合对于将黏着连接复合物转运到细胞表面是必需的，而与肌动蛋白的结合对于向细胞-细胞接触位点的易位是必需的。总的来说，我们的结果表明 JNK 影响α-连环蛋白与黏着连接复合物的关联并调节黏着连接。
