JNK regulates binding of α-catenin to adherens junctions and cell-cell adhesion
JNK regulates binding of α-catenin to adherens junctions and cell-cell adhesion
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DOI：
10.1096/fj.10-161380
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发表时间：
2011-02-01
期刊：
影响因子：
4.8
通讯作者：
Andreadis, Stelios T.
中科院分区：
文献类型：
--
作者：
Lee, Meng-Horng;Padmashali, Roshan;Andreadis, Stelios T.
我们最近报道了c-Jun氨基末端激酶(JNK)与黏附连接相关，并在丝氨酸33/37和苏氨酸41处磷酸化β-连环蛋白。在这里，我们报告了抑制JNK导致黏附连接的形成，伴随着α-连环蛋白从β-连环蛋白/E-钙粘蛋白复合体中解离出来，并增加了α-连环蛋白与细胞骨架的结合。相反，JNK的激活增加了α-连环蛋白与β-连环蛋白的结合，这一结合可被JNK抑制剂SP600125或JNK siRNA所阻断。此外，抑制JNK不能在α-连环蛋白缺失或被击倒的细胞中导致粘连连接的形成。相反，α-连环蛋白的引入恢复了细胞对JNK抑制的反应性，并导致了细胞间的黏附。结构域缺失突变体的实验表明，α-连环蛋白与β-连环蛋白的结合是将粘连连接复合体运输到细胞表面所必需的，而与肌动蛋白结合是运输到细胞-细胞接触部位所必需的。总之，我们的结果表明，JNK影响α-连环蛋白与黏附连接复合体的结合，并调节黏附连接。-Lee，M.H.，Padmashali，R.，Koria，P.，Andreadis，S.T.JNK调节α-连环蛋白与黏附连接的结合和细胞与细胞的黏附。FASE B J.25,613-623(2011)。Www.fasebj.org
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