A β-catenin identified by functional rather than sequence criteria and its role in Wnt/MAPK signaling
A β-catenin identified by functional rather than sequence criteria and its role in Wnt/MAPK signaling
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DOI：
10.1016/j.cell.2005.03.029
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发表时间：
2005-06-03
期刊：
影响因子：
64.5
通讯作者：
Kimble, J
中科院分区：
文献类型：
--
作者：
Kidd, AR;Miskowski, JA;Kimble, J
WNT/MAPK信号是线虫Wnt信号的一种常见变体，在脊椎动物中也被发现。在线虫发育过程中，sys-1基因与Wnt/MAPK信号一起控制细胞命运。我们报道了sys-1的氨基酸序列是新的，但sys-1的功能是P-catenin：sys-1挽救了bar-1/β-catenin缺失的突变体，结合了POP-1/TCFβ-catenin结合域，并共同激活了POP-1依赖的转录。此外，我们还提供了遗传和分子证据，证明sys-1水平对POP-1的活性至关重要。我们的结果表明，Wnt/MAPK信号促进POP-1从细胞核输出，以适应其sys-1/β-catenin转录共激活因子的有限可用性。Ys-1/β-catenin的发现扩展了我们对β-catenins的定义，并将Wnt信号的规范机制与非规范的Wnt/MAPK机制结合在一起。我们讨论了类似的途径可以在动物发育中广泛使用的想法。
Wnt/MAPK signaling is a common variant of Wnt signaling, in C. elegans and has been implicated in vertebrates. The sys-1 gene works with Wnt/MAPK signaling to control cell fates during C. elegans development. We report that the SYS-1 amino acid sequence is novel but that SYS-1 functions as P-catenin: SYS-1 rescues a bar-1/beta-catenin null mutant, binds the POP-1/TCF beta-catenin binding domain, and coactivates POP-1-dependent transcription. Moreover, we provide genetic and molecular evidence that SYS-1 levels are crucial to POP-1 activity. Our results suggest that Wnt/MAPK signaling promotes POP-1 export from the nucleus to accommodate the limiting availability of its SYS-1/beta-catenin transcriptional coactivator. Discovery of SYS-1/beta-catenin extends our definition of beta-catenins and brings together aspects of the canonical mechanism for Wnt signaling with the noncanonical Wnt/ MAPK mechanism. We discuss the idea that a similar pathway may be employed broadly in animal development.