Department for Molecular Biomedical Research, VIB, B-9052 Ghent, Belgium.
Front Biosci (Landmark Ed). 2012 Jan 1;17(5):1669-94. doi: 10.2741/4012.
The functions of many organs depend on the generation of an epithelium. The transition from a set of loosely connected nonpolarized cells to organized sheets of closely associated polarized epithelial cells requires the assembly of specialized cell junctions. In vertebrates, three major types of junctions are responsible for epithelial integrity: adherens junctions, tight junctions, and desmosomes. p120 catenin (p120ctn) is an Armadillo family member and a component of the cadherin-catenin complex in the adherens junction. It fulfils pleiotropic functions according to its subcellular localization: modulating the turnover rate of membrane-bound cadherins, regulating the activation of small RhoGTPases in the cytoplasm, and modulating nuclear transcription. Over the last two decades, knowledge of p120ctn obtained from in vitro experiments has been confirmed and extended by using different animal models. It has become clear that p120ctn is essential for normal development and homeostasis, at least in frog and mammals. p120ctn is a Src substrate that can be phosphorylated at different tyrosine, serine and threonine residues and can dock various kinases and phosphatases. Thereby, p120ctn regulates the phosphorylation status and the junctional stability of the cadherin-catenin complex. Multiple p120ctn isoforms are generated by alternative splicing, which allows the translation to be initiated from four start codons and enables the inclusion of four alternatively used exons. We will discuss the effects of different p120ctn isoforms on cadherin turnover and intracellular signaling, in particular RhoGTPase activity and phosphorylation events.
许多器官的功能依赖于上皮细胞的产生。从一组松散连接的非极化细胞到紧密相关的极化上皮细胞组织的转变需要专门的细胞连接的组装。在脊椎动物中，三种主要类型的连接负责上皮完整性：黏附连接、紧密连接和桥粒连接。p120 连环蛋白（p120ctn）是 Armadillo 家族的成员，也是黏附连接中钙粘蛋白-连环蛋白复合物的组成部分。根据其亚细胞定位，它具有多种功能：调节膜结合钙粘蛋白的周转率、调节细胞质中小 RhoGTPase 的激活、以及调节核转录。在过去的二十年中，通过使用不同的动物模型，已经从体外实验中获得了关于 p120ctn 的知识，并得到了证实和扩展。很明显，p120ctn 对正常发育和内稳态是必不可少的，至少在青蛙和哺乳动物中是这样。p120ctn 是Src 的底物，可以在不同的酪氨酸、丝氨酸和苏氨酸残基上磷酸化，并可以对接各种激酶和磷酸酶。因此，p120ctn 调节钙粘蛋白-连环蛋白复合物的磷酸化状态和连接稳定性。通过选择性剪接产生多种 p120ctn 异构体，这允许从四个起始密码子开始翻译，并允许包括四个选择性使用的外显子。我们将讨论不同的 p120ctn 异构体对钙粘蛋白周转和细胞内信号转导的影响，特别是 RhoGTPase 活性和磷酸化事件。
