Takada Ritsuko, Hijikata Hiroko, Kondoh Hisato, Takada Shinji
Okazaki Institute for Integrative Bioscience, National Institutes of Natural Sciences, Okazaki, Aichi 444-8787, Japan.
Genes Cells. 2005 Sep;10(9):919-28. doi: 10.1111/j.1365-2443.2005.00889.x.
Both Wnt ligands and Frizzled (Fz) receptors each constitute a large family in vertebrates, but the receptor specificity of each Wnt has remained largely unknown. Here, we examined the receptor specificity of two typical Wnts, Wnt-3a and Wnt-5a, in signal transmission. To investigate systematically the combinatorial effects of these Wnts, various Fzs on canonical Wnt/beta-catenin signaling, we analyzed the ability of these Wnt proteins to increase stability of armadillo/beta-catenin proteins in Drosophila S2 cells expressing vertebrate Fzs. Wnt-3a increases the amount of armadillo proteins in cells expressing Fzs 4, 5 and 8, but not Fzs 3 and 6; whereas Wnt-5a does not increase it in any cell line. In contrast, both Wnt-3a and Wnt-5a increase the phosphorylation of Dsh in combination with most of the Fzs. This Dsh phosphorylation is abrogated by decreasing the levels of casein kinase I alpha by double-stranded RNA-mediated translational interference. These observations indicate that both Wnt proteins can interact with the majority of Fz receptors and elicit signaling reactions exemplified by Dsh phosphorylation but that the stabilization of beta-catenin/armadillo proteins in the Wnt/beta-catenin signaling occurs only when specific combinations of Wnt and Fz meet.
在脊椎动物中，Wnt配体和卷曲蛋白（Fz）受体各自都构成一个大家族，但每种Wnt的受体特异性在很大程度上仍不清楚。在这里，我们研究了两种典型的Wnt，即Wnt-3a和Wnt-5a在信号转导中的受体特异性。为了系统地研究这些Wnt与各种Fz对经典Wnt/β-连环蛋白信号传导的组合效应，我们分析了这些Wnt蛋白在表达脊椎动物Fz的果蝇S2细胞中增加犰狳蛋白/β-连环蛋白稳定性的能力。Wnt-3a能增加表达Fz 4、5和8的细胞中犰狳蛋白的量，但不能增加表达Fz 3和6的细胞中的量；而Wnt-5a在任何细胞系中都不能增加其含量。相反，Wnt-3a和Wnt-5a与大多数Fz结合时都会增加Dsh的磷酸化。通过双链RNA介导的翻译干扰降低酪蛋白激酶Iα的水平可消除这种Dsh磷酸化。这些观察结果表明，两种Wnt蛋白都能与大多数Fz受体相互作用，并引发以Dsh磷酸化为例的信号反应，但只有当Wnt和Fz的特定组合相遇时，Wnt/β-连环蛋白信号传导中β-连环蛋白/犰狳蛋白的稳定才会发生。
