THE IDENTIFICATION OF 2 NOVEL LIGANDS OF THE FGF RECEPTOR BY A YEAST SCREENING METHOD AND THEIR ACTIVITY IN XENOPUS DEVELOPMENT
THE IDENTIFICATION OF 2 NOVEL LIGANDS OF THE FGF RECEPTOR BY A YEAST SCREENING METHOD AND THEIR ACTIVITY IN XENOPUS DEVELOPMENT
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DOI：
10.1016/0092-8674(95)90102-7
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发表时间：
1995-11-17
期刊：
影响因子：
64.5
通讯作者：
KIRSCHNER, MW
中科院分区：
文献类型：
--
作者：
KINOSHITA, N;MINSHULL, J;KIRSCHNER, MW
我们在酵母中开发了一种功能筛选方法来鉴定受体酪氨酸激酶的配体，利用这种方法，我们克隆了两个激活成纤维细胞生长因子（FGF）受体的爪蟾基因。这些编码新的分泌蛋白，被命名为FRL1和FRL2，分别与表皮生长因子和血管生成素/核糖核酸酶家族有远亲关系。这两种基因都能激活爪蟾卵母细胞和酵母中的FGF受体。过表达诱导爪蟾外植体中胚层和神经特异性基因诱导被FGF受体的显性阴性抑制剂阻断。FRL1在原肠胚期和神经胚期广泛表达，而FRL2主要在轴向中胚层和后期的脑中表达。我们的研究结果表明，尽管FRL1和FRL2与FGF缺乏相似性，但它们是FGF受体的配体，在发育过程中发挥着不同的作用。
We have developed a functional screen in yeast to identify ligands for receptor tyrosine kinases, Using this method, we cloned two Xenopus genes that activate the fibroblast growth factor (FGF) receptor. These encode novel secreted proteins, designated FRL1 and FRL2, distantly related to the epidermal growth factor and angiogenin/ribonuclease families, respectively. Both genes activate the FGF receptor in Xenopus oocytes as well as in yeast. Overexpression induces mesoderm and neural-specific genes in Xenopus explants; induction Is blocked by a dominant negative inhibitor of the FGF receptor. FRL1 is broadly expressed during gastrulation and neurulation, while FRL2 is expressed principally in the axial mesoderm and brain at later stages. Our results indicate that despite their lack of similarity with FGF, FRL1 and FRL2 are ligands for the FGF receptor that play distinct roles in development.