THE IDENTIFICATION OF 2 NOVEL LIGANDS OF THE FGF RECEPTOR BY A YEAST SCREENING METHOD AND THEIR ACTIVITY IN XENOPUS DEVELOPMENT

被引:131
作者
KINOSHITA, N [1 ]
MINSHULL, J [1 ]
KIRSCHNER, MW [1 ]
机构
[1] UNIV CALIF SAN FRANCISCO,DEPT PHYSIOL,SAN FRANCISCO,CA 94143
关键词
D O I
10.1016/0092-8674(95)90102-7
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:621 / 630
页数:10
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