A p120-catenin-CK1ε complex regulates Wnt signaling
A p120-catenin-CK1ε complex regulates Wnt signaling
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DOI：
10.1242/jcs.067512
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发表时间：
2010-08-01
影响因子：
4
通讯作者：
Dunach, Mireia
中科院分区：
文献类型：
--
作者：
Casagolda, David;del Valle-Perez, Beatriz;Dunach, Mireia
p120-catenin是调节E-钙粘蛋白功能和稳定性的E-钙粘蛋白相关蛋白。我们在这里描述了p120-catenin是Wnt信号通路所必需的。p120-连环蛋白结合并被CK 1 β磷酸化以响应Wnt 3a。p120-连环蛋白还与Wnt共受体LRP 5/6相关，这是一种由E-钙粘蛋白介导的相互作用，显示了粘附连接和Wnt受体之间的意外物理联系。p120-连环蛋白的消耗消除了CK 1 β与LRP 5/6的结合，并阻止了Wnt 3a刺激后CK 1 β的活化。p120-连环蛋白的消除也抑制对Wnt的早期反应，如LRP 5/6和Dv 1 -2磷酸化和轴蛋白向信号体的募集，以及后期效应，如β-连环蛋白稳定。此外，由于CK 1 β也是E-钙粘蛋白磷酸化所必需的，这是一种降低β-连环蛋白亲和力的修饰，p120-连环蛋白缺失即使在β-连环蛋白降解不存在的情况下也会阻止β-连环蛋白转录活性的增加。因此，这些结果证明了p120-连环蛋白在Wnt信号传导中的一种新的和关键的功能，并揭示了该因子与β-连环蛋白稳定性不同的β-连环蛋白转录活性的额外调节点。
p120-catenin is an E-cadherin-associated protein that modulates E-cadherin function and stability. We describe here that p120-catenin is required for Wnt pathway signaling. p120-catenin binds and is phosphorylated by CK1 epsilon in response to Wnt3a. p120-catenin also associates to the Wnt co-receptor LRP5/6, an interaction mediated by E-cadherin, showing an unexpected physical link between adherens junctions and a Wnt receptor. Depletion of p120-catenin abolishes CK1 epsilon binding to LRP5/6 and prevents CK1 epsilon activation upon Wnt3a stimulation. Elimination of p120-catenin also inhibits early responses to Wnt, such as LRP5/6 and Dv1-2 phosphorylation and axin recruitment to the signalosome, as well as later effects, such as beta-catenin stabilization. Moreover, since CK1 epsilon is also required for E-cadherin phosphorylation, a modification that decreases the affinity for beta-catenin, p120-catenin depletion prevents the increase in beta-catenin transcriptional activity even in the absence of beta-catenin degradation. Therefore, these results demonstrate a novel and crucial function of p120-catenin in Wnt signaling and unveil additional points of regulation by this factor of beta-catenin transcriptional activity different of beta-catenin stability.