Phosphorylation by the β-catenin/MAPK complex promotes 14-3-3-mediated nuclear export of TCF/POP-1 in signal-responsive cells in C-elegans
Phosphorylation by the β-catenin/MAPK complex promotes 14-3-3-mediated nuclear export of TCF/POP-1 in signal-responsive cells in C-elegans
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DOI：
10.1016/s0092-8674(04)00203-x
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发表时间：
2004-04-02
期刊：
影响因子：
64.5
通讯作者：
Lin, F
中科院分区：
文献类型：
--
作者：
Lo, MC;Gay, F;Lin, F
在秀丽隐杆线虫胚胎中，Wnt/MAPK信号通路下调TCF/LEF转录因子POP-1，导致信号应答细胞中的核水平低于姐妹细胞。尽管β -连环蛋白WRM-1是POP-1下调所必需的，但这两种蛋白之间的直接相互作用似乎并不需要，因为在早期胚胎中，POP-1的β -连环蛋白相互作用域对于POP-1下调和功能都是必不可少的。我们在这里表明，WRM-1通过促进MAP激酶lit1的磷酸化以及随后通过14-3-3蛋白PAR-5的核输出来下调POP-1。在信号应答细胞中，我们还检测到核lit1的同步上调，这依赖于Wnt/MAPK信号传导。我们的研究结果表明，Wnt/MAPK信号在应答细胞中下调POP-1水平，部分原因是通过增加核lit1水平，从而增加POP-1磷酸化和par -5介导的核输出。
In C. elegans embryos, a Wnt/MAPK signaling pathway downregulates the TCF/LEF transcription factor POP-1, resulting in a lower nuclear level in signal-responsive cells compared to their sisters. Although the beta-catenin WRM-1 is required for POP-1 down-regulation, a direct interaction between these two proteins does not seem to be required, as the beta-catenin-interacting domain of POP-1 is dispensable for both POP-1 downregulation and function in early embryos. We show here that WRM-1 downregulates POP-1 by promoting its phosphorylation by the MAP kinase LIT-1 and subsequent nuclear export via a 14-3-3 protein, PAR-5. In signal-responsive cells, we also detect a concurrent upregulation of nuclear LIT-1 that is dependent on Wnt/MAPK signaling. Our results suggest a model whereby Wnt/MAPK signaling downregulates POP-1 levels in responsive cells, in part by increasing nuclear LIT-1 levels, thereby increasing POP-1 phosphorylation and PAR-5-mediated nuclear export.