van den Heuvel M, Ingham P W
Molecular Embryology Laboratory, Imperial Cancer Research Fund, London, UK.
Nature. 1996 Aug 8;382(6591):547-51. doi: 10.1038/382547a0.
Members of the Hedgehog family of secreted proteins control a number of important inductive interactions in the development of both vertebrates and Drosophila, but little is known about the ways in which their signalling activities are transduced. In Drosophila, hedgehog is one of the segment-polarity genes, mutations of which disrupt the pattern and polarity of individual embryonic segments and their adult derivatives; several of these genes have been implicated in transduction of the hedgehog signal. Here we show that the segment-polarity gene smoothened is required for the response of cells to hedgehog signalling during the development of both the embryonic segments and imaginal discs. Sequence analysis of the smoothened transcription unit reveals a single open reading frame encoding a protein with seven putative transmembrane domains. This structure is typical of G-protein-coupled receptors, suggesting that the Smoothened protein may act as a receptor for the Hedgehog ligand.
分泌蛋白刺猬家族的成员在脊椎动物和果蝇的发育过程中控制着许多重要的诱导相互作用，但对于它们的信号传导活性是如何转导的却知之甚少。在果蝇中，刺猬基因是节段极性基因之一，其突变会破坏单个胚胎节段及其成虫衍生物的模式和极性；其中几个基因与刺猬信号的转导有关。我们在此表明，节段极性基因“平滑化”在胚胎节段和成虫盘的发育过程中，对于细胞对刺猬信号的反应是必需的。对“平滑化”转录单位的序列分析揭示了一个单一的开放阅读框，其编码一种具有七个推定跨膜结构域的蛋白质。这种结构是G蛋白偶联受体的典型结构，表明“平滑化”蛋白可能作为刺猬配体的受体发挥作用。
