Post-translational palmitoylation and glycosylation of Wnt-5a are necessary for its signalling
Post-translational palmitoylation and glycosylation of Wnt-5a are necessary for its signalling
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DOI：
10.1042/bj20061476
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发表时间：
2007-03-15
影响因子：
4.1
通讯作者：
Kikuchi, Akira
中科院分区：
文献类型：
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作者：
Kurayoshi, Manabu;Yamamoto, Hideki;Kikuchi, Akira
WNT-5a是一种具有代表性的配体，在WRIT信号转导中激活β-连环蛋白非依赖性途径。本文研究了翻译后修饰在WNT-5a作用中的作用。我们发现，WNT-5a在Cys(104)上被棕榈酸酯修饰，在Asn(114)、Asn(120)、Asn(311)和Asn(325)上用葡聚糖修饰。棕榈酰化对WNT-5a的分泌不是必需的，但对于其抑制依赖Wnt-3a的T细胞因子转录活性和刺激细胞迁移是必需的。WNT-5a激活粘着斑激酶，这种激活也需要棕榈酰化。野生型Wnt-5a可诱导Fz(Frizzled5)5内化，而缺失棕榈酰化位点的Wnt-5a突变体则不能。此外，Wnt-5a与Fz5胞外区的结合需要Wnt-5a的棕榈酰化。这些结果表明，WNT-5a的棕榈酰化对于在细胞表面水平触发信号是重要的，因此，未经脂质修饰的WNT-5a不能激活细胞内的信号级联。相反，糖基化对WNT-5a的分泌是必需的，但对WNT-5a的作用不是必需的。因此，WNT-5a的翻译后棕榈酰化和糖基化对WNT-5a的作用和分泌是重要的。
Wnt-5a is a representative ligand that activates a beta-catenin-independent pathway in Writ signalling. In the present paper, the roles of the post-translational modifications in the actions of Wnt-5a were investigated. We found that Wnt-5a is modified with palmitate at Cys(104) and glycans at Asn(114), Asn(120), Asn(311) and Asn(325). The palmitoylation was not essential for the secretion of Wnt-5a, but was necessary for its ability to suppress Wnt-3a-dependent T- cell factor transcriptional activity and to stimulate cell migration. Wnt-5a activated focal adhesion kinase and this activation also required palmitoylation. Wild-type Wnt-5a induced the internalization of Fz (Frizzled) 5, but a Wnt-5a mutant that lacks the palmitoylation site did not. Furthermore, the binding of Wnt-5a to the extracellular domain of Fz5 required palmitoylation of Wnt-5a. These results indicate that palmitoylation of Wnt-5a is important for the triggering of signalling at the cell surface level and, therefore, that the lipid-unmodified form of Wnt-5a cannot activate intracellular signal cascades. In contrast, glycosylation was necessary for the secretion of Wnt-5a, but not essential for the actions of Wnt-5a. Thus the post-translational palmitoylation and glycosylation of Wnt-5a are important for the actions and secretion of Wnt-5a.