Sef is a feed back-induced antagonist of Ras/MAPK-mediated FGF signalling
Sef is a feed back-induced antagonist of Ras/MAPK-mediated FGF signalling
复制标题
DOI：
10.1038/ncb750
复制
发表时间：
2002-02-01
影响因子：
21.3
通讯作者：
Thisse, C
中科院分区：
文献类型：
--
作者：
Fürthauer, M;Lin, W;Thisse, C
成纤维细胞生长因子（FGF）是控制细胞增殖、迁移、分化和胚胎形成的多营养生长因子（1）。在早期斑马鱼胚胎发育过程中，FGF通过控制腹侧骨形态发生蛋白（BMP）的表达来调节背腹侧模式（2，3）。FGF通过结合和激活高亲和力酪氨酸激酶受体发挥作用（4）。FGF活性受Sprouty家族成员的负调节，Sprouty家族成员拮抗受体酪氨酸激酶诱导的Ras信号传导（3，5 -8）。在胚胎发育过程中，他们的表达模式的相似性的基础上，我们已经确定了五个基因，定义一个synexpression组-fgf 8，fgf 3，sprouty 2，sprouty 4，以及一个新的基因，sef（类似于FGF基因的表达）。Sef编码一个保守的假定跨膜蛋白，与白细胞介素17受体的胞内结构域具有序列相似性。在这里，我们表明，在斑马鱼，Sef功能作为反馈诱导的拮抗剂Ras/Raf/MEK/MAPK介导的FGF信号。
Fibroblast growth factors (FGFs) are pleiotrophic growth factors that control cell proliferation, migration, differentiation and embryonic patterning(1). During early zebrafish embryonic development, FGFs regulate dorsoventral patterning by controlling ventral bone morphogenetic protein (BMP) expression(2,3). FGFs function by binding and activating high-affinity tyrosine kinase receptors(4). FGF activity is negatively regulated by members of the Sprouty family, which antagonize Ras signalling induced by receptor tyrosine kinases(3,5-8). On the basis of similarities in their expression patterns during embryonic development, we have identified five genes that define a synexpression group - fgf8, fgf3, sprouty2, sprouty4, as well as a novel gene, sef (similar expression to fgf genes). Sef encodes a conserved putative transmembrane protein that shares sequence similarities with the intracellular domain of the interleukin 17 receptors. Here we show that in zebrafish, Sef functions as a feedback-induced antagonist of Ras/Raf/MEK/MAPK-mediated FGF signalling.