Identification of the stef gene that encodes a novel guanine nucleotide exchange factor specific for Rac1
Identification of the stef gene that encodes a novel guanine nucleotide exchange factor specific for Rac1
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DOI：
10.1074/jbc.274.25.17837
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发表时间：
1999-06-18
影响因子：
4.8
通讯作者：
Hama, C
中科院分区：
文献类型：
--
作者：
Hoshinoso, M;Sone, M;Hama, C
Rho家族GTP酶通过改变肌动蛋白细胞骨架网络的组织来响应细胞外信号，参与多种细胞事件。然而，目前还不清楚它们的活动是如何在空间和时间上受到调节的。本文报道了一种新的鸟嘌呤核苷酸交换因子Rad，Stef，它在氨基酸序列和模块结构上与小鼠Tiam1和果蝇SIF蛋白相关。STEF蛋白含有两个Pleckstrin同源结构域，一个是PDZ结构域，一个是DBL同源结构域。体外试验表明，Stef蛋白特异性地促进了GDP与rac1的解离，但不能促进RhoA或Cdc42的解离。在培养细胞中表达截短的Stef蛋白会引起肌动蛋白定位改变的膜褶皱，这意味着该蛋白在体内也激活了Rad。在胚胎发育过程中，在小鼠的受限部位观察到了Stef转录本，包括软骨组织和中枢神经系统的皮质板。这些发现表明，Stef蛋白参与了几个发育中组织的细胞事件的控制，可能通过激活Rad改变了肌动蛋白细胞骨架网络。
The Rho family GTPases are involved in a variety of cellular events by changing the organization of actin cytoskeletal networks in response to extracellular signals. However, it is not clearly known how their activities are spatially and temporally regulated. Here we report the identification of a novel guanine nucleotide exchange factor for Rad, STEF, which is related in overall amino acid sequence and modular structure to mouse Tiam1 and Drosophila SIF proteins. STEF protein contains two pleckstrin homology domains, a PDZ domain and a Dbl homology domain. The in vitro assay showed that STEF protein specifically enhanced the dissociation of GDP from Rac1 but not that from either RhoA or Cdc42. Expression of a truncated STEF protein in culture cells induced membrane ruffling with altered actin localization, which implies that this protein also activates Rad in vivo. The stef transcript was observed in restricted parts of mice, including cartilaginous tissues and the cortical plate of the central nervous system during embryogenesis. These findings suggested that STEF protein participates in the control of cellular events in several developing tissues, possibly changing the actin cytoskeletal network by activating Rad.