Phosphorylation and isoform use in p120-catenin during development and tumorigenesis.
Phosphorylation and isoform use in p120-catenin during development and tumorigenesis.
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DOI：
10.1016/j.bbamcr.2015.10.008
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发表时间：
2016-01
期刊：
影响因子：
--
通讯作者：
McCrea PD
中科院分区：
文献类型：
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作者：
Hong JY;Oh IH;McCrea PD
P120-连环蛋白对于脊椎动物发育、调节钙粘蛋白和小 GTP 酶功能至关重要，并且越来越多的证据表明它也在细胞核中发挥作用。解决 p120-连环蛋白功能的一个复杂性是它有许多亚型，包括可选剪接事件、翻译起始的替代点和二次修饰。在这篇综述中，我们重点关注蛋白质翻译起始或 RNA 转录物早期剪接的选择如何与包含已建立或推定的调节磷酸化位点的一级序列相关。虽然某些 p120 磷酸化事件通过已知的激酶/磷酸酶产生并具有明确的结果，但在大多数情况下，其功能后果仍有待确定。在这篇综述中，我们提供了 p120 同工型的示例，因为它们与磷酸化事件相关，从而与同工型依赖性蛋白质-蛋白质关联和下游功能相关。我们还提供了决定 p120 磷酸化状态的上游途径的视图，从而对发育和疾病产生影响。由于 p120 亚家族的其他成员以及 plakophilin 亚家族的相关连环蛋白经历类似的加工和磷酸化，因此关于 p120 的了解将在脊椎动物中具有广泛的相关性。
P120-catenin is essential to vertebrate development, modulating cadherin and small-GTPase functions, and growing evidence points also to roles in the nucleus. A complexity in addressing p120-catenin’s functions is its many isoforms, including optional splicing events, alternative points of translational initiation, and secondary modifications. In this review, we focus upon how choices in the initiation of protein translation, or the earlier splicing of the RNA transcript, relates to primary sequences that harbor established or putative regulatory phosphorylation sites. While certain p120 phosphorylation events arise via known kinases/ phosphatases and have defined outcomes, in most cases the functional consequences are still to be established. In this review, we provide examples of p120-isoforms as they relate to phosphorylation events, and thereby to isoform dependent protein-protein associations and downstream functions. We also provide a view of upstream pathways that determine p120’s phosphorylation state, thereby having an impact upon development and disease. Because other members of the p120 subfamily undergo similar processing and phosphorylation, as well as related catenins of the plakophilin subfamily, what is learned regarding p120 will by extension have wide relevance in vertebrates.