Characterization of a novel Ras-binding protein Ce-FLI-1 comprising leucine-rich repeats and gelsolin-like domains

Characterization of a novel Ras-binding protein Ce-FLI-1 comprising leucine-rich repeats and gelsolin-like domains
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DOI:
10.1006/bbrc.1999.0420
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发表时间:
1999-04-02
影响因子:
3.1
通讯作者:
Kataoka, T
Kataoka, T
中科院分区:
生物学4区
文献类型:
--
作者:
Goshima, M;Kariya, K;Kataoka, T

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Ras蛋白从酵母到哺乳动物都是保守的,并参与肌动蛋白细胞骨架的调节。黑腹果蝇(Drosophila melanogaster)及其在秀丽隐杆线虫(Caenorhabditis elegans)和人类中的同源基因fli-1编码的蛋白(fli-1)包含一个富含亮氨酸重复序列(lrr)结构域和一个凝胶样结构域的融合。这个LRRs结构域与参与ras介导的信号传导的三种蛋白质高度同源;酿酒酵母腺苷酸环化酶,秀丽隐杆线虫的sr -8和哺乳动物的RSP-1。本研究报告了秀丽隐杆线虫FLI-1 (Ce-FLI-1)的LRRs结构域与Has (K-d = 11 nM)直接相关,当其过表达时,可抑制携带激活的RAS2基因(RAS2(Val-19))的酵母细胞的热休克敏感表型。此外,ce - fl -1的凝胶样结构域被证明具有不依赖于Ca2+的g -actin结合活性以及f -actin结合和切断活性。FLI-1可能通过Has参与肌动蛋白细胞骨架的调控。(C) 1999学术出版社。
Ras proteins are conserved from yeasts to mammals and implicated in regulation of the actin cytoskeleton. The flightless-1 (fli-1) gene of Drosophila melanogaster and its homologs in Caenorhabditis elegans and humans encode proteins (FLI-1) comprising a fusion of a leucine-rich repeats (LRRs) domain and a gelsolin-like domain. This LRRs domain is highly homologous to those of three proteins involved in Ras-mediated signaling; Saccharomyces cerevisiae adenylyl cyclase, C. elegans SUR-8, and mammalian RSP-1. Here we report that the LRRs domain of C. elegans FLI-1 (Ce-FLI-1) associates directly with Has (K-d = 11 nM) and, when overexpressed, suppresses the heat shock sensitive phenotype of yeast cells bearing the activated RAS2 gene (RAS2(Val-19)). Further, the gelsolin-like domain of Ce-FLI-1 is shown to possess a Ca2+-independent G-actin-binding activity as well as F-actin-binding and -severing activities. FLI-1 may be involved in regulation of the actin cytoskeleton through Has. (C) 1999 Academic Press.