Naked cuticle encodes an inducible antagonist of Wnt signalling
Naked cuticle encodes an inducible antagonist of Wnt signalling
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DOI：
10.1038/35001615
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发表时间：
2000-02-17
期刊：
影响因子：
64.8
通讯作者：
Scott, MP
中科院分区：
文献类型：
--
作者：
Zeng, WL;Wharton, KA;Scott, MP
在动物发育过程中，细胞必须对局部分泌信号做出适当的反应。对Hedgehog、转化生长因子-β、表皮生长因子和成纤维细胞生长因子/Ras信号的适当反应需要同源诱导型拮抗剂，如Patched、Dad、Argos和Sprouty（1）。Wnt信号在发育和肿瘤形成中至关重要（2）。在这里，我们表明，裸角质层（nkd），果蝇节极性基因，编码的Wnt信号Wingless（Wg）的诱导型拮抗剂。在果蝇胚胎和成虫盘中，Wg诱导nkd转录。在胚胎中，nkd功能下降的影响类似于过量的Wg;在后期阶段，这种下降似乎没有影响。相反，果蝇中Nkd的过量产生和脊椎动物非洲爪蟾中Nkd的错误表达导致类似于Wg/Wnt功能丧失的表型。nkd编码一种具有单一EF手（钙结合基序）的蛋白质，该蛋白质与肉豆蔻酰开关蛋白的recoverin家族最相似。因此，Nkd可能将离子通量与Wnt信号的效力、持续时间或分布的调节联系起来。信号诱导型反馈拮抗剂如nkd可限制Wnt蛋白在发育和疾病中的作用。
During animal development, cells have to respond appropriately to localized secreted signals. Proper responses to Hedgehog, transforming growth factor-beta, epidermal growth factor and fibroblast growth factor/Ras signals require cognate inducible antagonists such as Patched, Dad, Argos and Sprouty(1). Wnt signals are crucial in development and neoplasia(2). Here we show that naked cuticle (nkd), a Drosophila segment-polarity gene, encodes an inducible antagonist for the Wnt signal Wingless (Wg). In fly embryos and imaginal discs nkd transcription is induced by Wg. In embryos, decreased nkd function has an effect similar to excess Wg; at later stages such a decrease appears to have no effect. Conversely, overproduction of Nkd in Drosophila and misexpression of Nkd in the vertebrate Xenopus laevis result in phenotypes resembling those of loss of Wg/Wnt function. nkd encodes a protein with a single EF hand (a calcium-binding motif) that is most similar to the recoverin family of myristoyl switch proteins. Nkd may therefore Link ion fluxes to the regulation of the potency, duration or distribution of Wnt signals. Signal-inducible feedback antagonists such as nkd may limit the effects of Wnt proteins in development and disease.