Identification and characterization of Ral-binding protein 1, a potential downstream target of Ral GTPases.

Identification and characterization of Ral-binding protein 1, a potential downstream target of Ral GTPases.
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Ral 结合蛋白 1(Ral GTPases 的潜在下游靶标)的鉴定和表征。

DOI:
10.1128/mcb.15.8.4578
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发表时间:
1995
影响因子:
5.3
通讯作者:
Feig,LA
Feig,LA
中科院分区:
生物学2区
文献类型:
--
作者:
Cantor,SB;Urano,T;Feig,LA

文献摘要

被引文献

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Ral蛋白构成了一个独特的ras相关gtpase家族。虽然在氨基酸序列上与Ras相似,但Ral蛋白被一种独特的核苷酸交换因子激活,并被一种独特的gtpase激活蛋白灭活。与Ras不同的是,当激活版本在细胞中表达时,它们不能促进转化灶。为了鉴定可能介导ral特异性功能的下游靶点,我们使用基于酿酒糖酵母菌的相互作用实验克隆了编码ral结合蛋白(RalBP1)的新cDNA。RalBP1特异性结合活性gtp结合形式的RalA,而不是在其假定的效应域具有点突变的突变Ral。除了Rho结合结构域外,RalBP1还含有一个Rho- gtpase激活蛋白结构域,该结构域优先与Rho家族成员CDC42相互作用。由于CDC42与芽位点选择inS有关。在哺乳动物细胞中,Ral可能通过与RalBP1的相互作用来调节肌动蛋白细胞骨架。
Ral proteins constitute a distinct family of Ras-related GTPases. Although similar to Ras in amino acid sequence, Ral proteins are activated by a unique nucleotide exchange factor and inactivated by a distinct GTPase-activating protein. Unlike Ras, they fail to promote transformed foci when activated versions are expressed in cells. To identify downstream targets that might mediate a Ral-specific function, we used aSaccharomyces cerevisiae-based interaction assay to clone a novel cDNA that encodes a Ral-binding protein (RalBP1). RalBP1 binds specifically to the active GTP-bound form of RalA and not to a mutant Ral with a point mutation in its putative effector domain. In addition to a Ral-binding domain, RalBP1 also contains a Rho-GTPase-activating protein domain that interacts preferentially with Rho family member CDC42. Since CDC42 has been implicated in bud site selection inS. cerevisiaeand filopodium formation in mammalian cells, Ral may function to modulate the actin cytoskeleton through its interactions with RalBP1.