Limited dishevelled/Axin oligomerization determines efficiency of Wnt/β-catenin signal transduction
Limited dishevelled/Axin oligomerization determines efficiency of Wnt/β-catenin signal transduction
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DOI：
10.7554/elife.55015
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发表时间：
2020-04-16
期刊：
影响因子：
7.7
通讯作者：
Weis, William, I
中科院分区：
文献类型：
--
作者：
Kan, Wei;Enos, Michael D.;Weis, William, I
在Wnt/ β -catenin信号传导中，转录辅激活因子β -catenin受其在一个复合物中的磷酸化调控，该复合物包括支架蛋白轴蛋白和相关激酶。Wnt与其辅助受体结合激活胞浆效应因子disheveled (Dvl)，导致轴蛋白的募集和β -连环蛋白磷酸化的抑制。这一过程需要Dvl和Axin中存在的同源DIX结构域的相互作用，但机制尚未明确。我们发现Dvl DIX在体外形成反平行的双链低聚物，并且细胞中的Dvl通常形成低聚物
In Wnt/beta-catenin signaling, the transcriptional coactivator beta-catenin is regulated by its phosphorylation in a complex that includes the scaffold protein Axin and associated kinases. Wnt binding to its coreceptors activates the cytosolic effector Dishevelled (Dvl), leading to the recruitment of Axin and the inhibition of beta-catenin phosphorylation. This process requires interaction of homologous DIX domains present in Dvl and Axin, but is mechanistically undefined. We show that Dvl DIX forms antiparallel, double-stranded oligomers in vitro, and that Dvl in cells forms oligomers typically