Tsinghua University, Beijing, China.
Cell Signal. 2010 May;22(5):717-27. doi: 10.1016/j.cellsig.2009.11.021. Epub 2009 Dec 13.
Wnt signaling controls a variety of developmental and homeostatic events. As a key component of Wnt signaling, Dishevelled (Dvl/Dsh) protein relays Wnt signals from receptors to downstream effectors. In the canonical Wnt pathway that depends on the nuclear translocation of beta-catenin, Dvl is recruited by the receptor Frizzled and prevents the constitutive destruction of cytosolic beta-catenin. In the non-canonical Wnt pathways such as Wnt-Frizzled/PCP (planar cell polarity) signaling, Dvl signals via the Daam1-RhoA axis and the Rac1 axis. In addition, Dvl plays important roles in Wnt-GSK3beta-microtubule signaling, Wnt-calcium signaling, Wnt-RYK signaling, Wnt-atypical PKC signaling, etc. Dvl also functions to mediate receptor endocytosis. To fulfill its multifaceted functions, it is not surprising that Dvl associates with various kinds of proteins. Its activity is also modulated dynamically by phosphorylation, ubiquitination and degradation. In this review, we summarize the current understanding of Dvl functions in Wnt signal transduction and its biological functions in mouse development, and also discuss the molecular mechanisms of its actions.
Wnt 信号通路控制着多种发育和稳态事件。作为 Wnt 信号通路的关键组成部分，Dvl（Dishevelled/Dsh）蛋白将 Wnt 信号从受体传递到下游效应物。在依赖于β-catenin 核易位的经典 Wnt 通路中，Dvl 被受体 Frizzled 募集，并阻止细胞质内β-catenin 的组成性破坏。在非经典的 Wnt 通路如 Wnt-Frizzled/PCP（平面细胞极性）信号通路中，Dvl 通过 Daam1-RhoA 轴和 Rac1 轴发出信号。此外，Dvl 在 Wnt-GSK3β-微管信号通路、Wnt-钙信号通路、Wnt-RYK 信号通路、Wnt-非典型 PKC 信号通路等方面也发挥着重要作用。Dvl 还参与调节受体内吞。为了实现其多方面的功能，Dvl 与各种蛋白质结合并不奇怪。其活性还通过磷酸化、泛素化和降解进行动态调节。在这篇综述中，我们总结了目前对 Dvl 在 Wnt 信号转导中的功能及其在小鼠发育中的生物学功能的理解，还讨论了其作用的分子机制。
