β-Arrestin and casein kinase 1/2 define distinct branches of non-canonical WNT signalling pathways
β-Arrestin and casein kinase 1/2 define distinct branches of non-canonical WNT signalling pathways
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DOI：
10.1038/embor.2008.193
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发表时间：
2008-12-01
期刊：
影响因子：
7.7
通讯作者：
Schulte, Gunnar
中科院分区：
文献类型：
--
作者：
Bryja, Vitezslav;Schambony, Alexandra;Schulte, Gunnar
最近在理解β-连环蛋白非依赖的WNT(非经典)信号方面的进展表明，WNT(非经典)信号的复杂性日益增加，这引发了如何诱导和调控单个非典型通路的问题。在这里，我们研究了细胞内信号成分，如β-arrestin(beta-arrestin)和Casein kinase1和2(CK1和CK2)是否有助于确定β连环蛋白非依赖性WNT信号到小GTPase RAC-1的信号特异性。我们的发现表明，β-ARR对于WNT/RAC-1信号转导是足够和必要的，酪蛋白激酶作为一个开关，阻止RAC-1的激活，并通过Disheveled(非洲爪哇中的DVL，xDSH)的磷酸化促进其他非规范的WNT途径。因此，我们的结果表明，β-ARR和CK1/2之间的平衡决定了WNT/RAC-1或其他非规范的WNT通路是否被激活。
Recent advances in understanding beta-catenin-independent WNT (non-canonical) signalling suggest an increasing complexity, raising the question of how individual non-canonical pathways are induced and regulated. Here, we examine whether intracellular signalling components such as beta-arrestin (beta-arr) and casein kinases 1 and 2 (CK1 and CK2) can contribute to determining signalling specificity in beta-catenin-independent WNT signalling to the small GTPase RAC-1. Our findings indicate that beta-arr is sufficient and required for WNT/RAC-1 signalling, and that casein kinases act as a switch that prevents the activation of RAC-1 and promotes other non-canonical WNT pathways through the phosphorylation of dishevelled (DVL, xDSH in Xenopus). Thus, our results indicate that the balance between beta-arr and CK1/2 determines whether WNT/RAC-1 or other non-canonical WNT pathways are activated.