GDNF signalling through the Ret receptor tyrosine kinase
GDNF signalling through the Ret receptor tyrosine kinase
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DOI：
10.1038/381789a0
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发表时间：
1996-06-27
期刊：
影响因子：
64.8
通讯作者：
Pachnis, V
中科院分区：
文献类型：
--
作者：
Durbec, P;MarcosGutierrez, CV;Pachnis, V
人类和小鼠的突变分析表明，受体酪氨酸激酶（RTK）超家族成员c-ret原癌基因的产物Ret（1）对肠神经系统和肾脏的发育至关重要（2-6）。尽管Ret在哺乳动物胚胎发生中的作用已经确定，但其同源配体目前尚不清楚。在这里，我们通过使用非洲爪蟾胚胎生物测定证明，胶质细胞系源性神经营养因子（GDNF）（7），转化生长因子（TGF）-β超家族的远缘成员，通过Ret RTK发出信号。此外，使用来自野生型和Ret缺陷小鼠胚胎的外植体培养物（4），我们表明正常的c-ret功能是外周神经系统中GDNF信号传导所必需的。我们的数据强烈地表明Ret是GDNF的功能性受体，并且GDNF除了在中枢神经系统神经元的分化和存活中的潜在作用之外（8-12），对肾脏器官形成和周围神经系统的发育具有深远的影响。
MUTATIONAL analysis in humans and mice has demonstrated that Ret, the product of the c-ret proto-oncogene, a member of the receptor tyrosine kinase (RTK) superfamily(1), is essential for development of the enteric nervous system and kidney(2-6). Despite the established role of Ret in mammalian embryogenesis, its cognate ligand(s) is currently unknown. Here we demonstrate, by using a Xenopus embryo bioassay, that glial-cell-line-derived neurotrophic factor (GDNF)(7), a distant member of the transforming growth factor(TGF)-beta superfamily, signals through the Ret RTK. Furthermore, using explant cultures from wild-type and Ret-deficient mouse embryos(4), we show that normal c-ret function is necessary for GDNF signalling in the peripheral nervous system, Our data strongly suggest that Ret is a functional receptor for GDNF, and that GDNF, in addition to its potential role in the differentiation and survival of central nervous system neurons(8-12), has profound effects on kidney organogenesis and the development of the peripheral nervous system.