Zeng W, Wharton K A, Mack J A, Wang K, Gadbaw M, Suyama K, Klein P S, Scott M P
Department of Developmental Biology, Howard Hughes Medical Institute, Beckman Center, Stanford University School of Medicine, California 94305, USA.
Nature. 2000 Feb 17;403(6771):789-95. doi: 10.1038/35001615.
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. Wnt signals are crucial in development and neoplasia. 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.
在动物发育过程中，细胞必须对局部分泌的信号做出适当反应。对刺猬蛋白、转化生长因子-β、表皮生长因子和成纤维细胞生长因子/Ras信号的正确反应需要同源诱导性拮抗剂，如帕奇蛋白、Dad、Argos和Sprouty。Wnt信号在发育和肿瘤形成中至关重要。在这里，我们表明，果蝇节段极性基因裸角质层（nkd）编码Wnt信号无翅（Wg）的诱导性拮抗剂。在果蝇胚胎和成虫盘（imaginal disc）中，nkd转录由Wg诱导。在胚胎中，nkd功能降低产生的效果与Wg过量相似；在后期阶段，这种降低似乎没有影响。相反，果蝇中Nkd的过量产生以及脊椎动物非洲爪蟾中Nkd的错误表达导致的表型类似于Wg/Wnt功能丧失的表型。nkd编码一种具有单个EF手型（一种钙结合基序）的蛋白质，该蛋白质与肉豆蔻酰开关蛋白的恢复蛋白家族最为相似。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。像nkd这样的信号诱导性反馈拮抗剂可能会限制Wnt蛋白在发育和疾病中的作用。
