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首页> 外文期刊>Cellular Signalling >Role of the Sec14-like domain of Dbl family exchange factors in the regulation of Rho family GTPases in different subcellular sites
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Role of the Sec14-like domain of Dbl family exchange factors in the regulation of Rho family GTPases in different subcellular sites

机译：Dbl家族交换因子的Sec14样结构域在不同亚细胞位点Rho家族GTPases调控中的作用

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摘要

Mechanisms underlying subcellular region-specific regulation of Rho family GTPases through Dbl family guanine nucleotide exchange factors (GEFs) remain totally unknown. Here we show that the Sec14-like domain, which lies in the N-terminus of the Dbl family GEFs Dbl and Ost, directs the subcellular localization of these GEFs and also their substrate Cdc42. When coexpressed with Cdc42 in human adenocarcinoma HeLa cells, Dbl-I and Ost-I, which lack the Sec14-like domain, translocated Cdc42 to the plasma membrane, where Dbl-I or Ost-I was colocalized. In marked contrast, Dbl-II and Ost-II, which contain the Sec14-like domain, were colocalized with Cdc42 in endomembrane compartments. Furthermore, ruffle membrane formation upon epidermal growth factor treatment was mediated by Dbl-I or Ost-I, but neither Dbl-II nor Ost-II, supporting a notion that GEFs with or without the Sec14-like domain are linked to different upstream signals. By employing a novel method to detect the active GTP-bound form of Cdc42 in situ, we demonstrate that Dbl-I and Ost-I, but neither Dbl-II nor Ost-II, indeed activate colocalized Cdc42. (C) 2004 Elsevier Inc. All rights reserved.
机译：通过Dbl家族鸟嘌呤核苷酸交换因子（GEFs）对Rho家族GTPases进行亚细胞区域特异性调节的机制尚不清楚。在这里，我们显示Sec14样域，位于Dbl家族GEFs Dbl和Ost的N末端，指导这些GEFs及其底物Cdc42的亚细胞定位。当在人类腺癌HeLa细胞中与Cdc42共表达时，缺少Sec14样结构域的Dbl-1和Ost-1将Cdc42转移到质膜，在那里Dbl-1或Ost-1共定位。与之形成鲜明对比的是，含有Sec14样结构域的Dbl-II和Ost-II与Cdc42在膜内区室共定位。此外，表皮生长因子治疗后的皱纹膜形成是由Dbl-I或Ost-I介导的，但Dbl-II和Ost-II均不介导，支持这样的观念：具有或不具有Sec14样结构域的GEF与不同的上游信号相关。通过采用一种新颖的方法来原位检测Cdc42的活性GTP结合形式，我们证明Dbl-I和Ost-I，但Dbl-II和Ost-II均未激活共定位的Cdc42。 （C）2004 Elsevier Inc.保留所有权利。

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