Conformational change of Dishevelled plays a key regulatory role in the Wnt signaling pathways.
Conformational change of Dishevelled plays a key regulatory role in the Wnt signaling pathways.
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Disheveled的构象变化在Wnt信号通路中发挥关键调节作用
DOI：
10.7554/elife.08142
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发表时间：
2015-08-22
期刊：
影响因子：
7.7
通讯作者：
Zheng JJ
中科院分区：
文献类型：
--
作者：
Lee HJ;Shi DL;Zheng JJ
细胞内信号传导分子Dishevelled（Dvl）通过其PDZ结构域介导经典和非经典Wnt信号传导。不同的途径在这一点上分歧的机制仍然不清楚。在这里，我们表明Dvl PDZ结构域的肽结合口袋可以被Dvl自身的高度保守的C-末端占据，诱导闭合构象。在非洲爪蟾中，Wnt调节的会聚延伸（CE）容易受到Dvl突变体的影响，所述Dvl突变体不能形成比野生型Dvl更闭合的构象。我们还证明，虽然Dvl与其他Wnt通路元件合作，以激活经典的Wnt信号，Dvl的开放构象更有效地激活Jun N-末端激酶（JNK）。这些结果表明，与Wnt信号通路中的其他参与者一起，Dvl的构象变化在非经典Wnt信号通路中调节Wnt刺激的JNK活性。DOI：http://dx.doi.org/10.7554/eLife.08142.001网站
The intracellular signaling molecule Dishevelled (Dvl) mediates canonical and non-canonical Wnt signaling via its PDZ domain. Different pathways diverge at this point by a mechanism that remains unclear. Here we show that the peptide-binding pocket of the Dvl PDZ domain can be occupied by Dvl's own highly conserved C-terminus, inducing a closed conformation. In Xenopus, Wnt-regulated convergent extension (CE) is readily affected by Dvl mutants unable to form the closed conformation than by wild-type Dvl. We also demonstrate that while Dvl cooperates with other Wnt pathway elements to activate canonical Wnt signaling, the open conformation of Dvl more effectively activates Jun N-terminal kinase (JNK). These results suggest that together with other players in the Wnt signaling pathway, the conformational change of Dvl regulates Wnt stimulated JNK activity in the non-canonical Wnt signaling. DOI: http://dx.doi.org/10.7554/eLife.08142.001