The Hippo Pathway Regulates Wnt/β-Catenin Signaling
The Hippo Pathway Regulates Wnt/β-Catenin Signaling
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DOI：
10.1016/j.devcel.2010.03.007
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发表时间：
2010-04-20
影响因子：
11.8
通讯作者：
Attisano, Liliana
中科院分区：
文献类型：
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作者：
Varelas, Xaralabos;Miller, Bryan W.;Attisano, Liliana
几种发育途径有助于调节组织生长和器官大小的过程。Hippo通路已经成为这样一个关键的调节器。然而，Hippo信号传导如何与其他途径整合以协调这些过程仍不清楚。在这里，我们表明Hippo通路通过促进细胞质中TAZ和DVL之间的相互作用来限制Wnt/β-连环蛋白信号传导。TAZ抑制CK 1 δ/ε介导的DVL磷酸化，从而抑制Wnt/β-连环蛋白信号传导。TAZ水平或Hippo信号传导的消除增强Wnt 3A刺激的DVL磷酸化、核β-连环蛋白和Wnt靶基因表达。缺乏Taz的小鼠发展为具有增强的细胞质和细胞核β-连环蛋白的多囊肾。此外，在果蝇中，Hippo信号调节Wg靶基因的表达。这些结果揭示了TAZ在调节Wnt信号传导中的细胞质功能，并强调了Hippo通路在协调形态发生信号传导与生长控制中的作用。
Several developmental pathways contribute to processes that regulate tissue growth and organ size. The Hippo pathway has emerged as one such critical regulator. However, how Hippo signaling is integrated with other pathways to coordinate these processes remains unclear. Here, we show that the Hippo pathway restricts Wnt/beta-Catenin signaling by promoting an interaction between TAZ and DVL in the cytoplasm. TAZ inhibits the CK1 delta/epsilon-mediated phosphorylation of DVL, thereby inhibiting Wnt/beta-Catenin signaling. Abrogation of TAZ levels or Hippo signaling enhances Wnt3A-stimulated DVL phosphorylation, nuclear beta-Catenin, and Wnt target gene expression. Mice lacking Taz develop polycystic kidneys with enhanced cytoplasmic and nuclear beta-Catenin. Moreover, in Drosophila, Hippo signaling modulates Wg target gene expression. These results uncover a cytoplasmic function of TAZ in regulating Wnt signaling and highlight the role of the Hippo pathway in coordinating morphogenetic signaling with growth control.