[Role of the multifunctional Trio protein in the control of the Rac1 and RhoA gtpase signaling pathways].

J M Bellanger, O Zugasti, J B Lazaro, S Diriong, N Lamb, C Sardet, A Debant
{"title":"[Role of the multifunctional Trio protein in the control of the Rac1 and RhoA gtpase signaling pathways].","authors":"J M Bellanger,&nbsp;O Zugasti,&nbsp;J B Lazaro,&nbsp;S Diriong,&nbsp;N Lamb,&nbsp;C Sardet,&nbsp;A Debant","doi":"","DOIUrl":null,"url":null,"abstract":"<p><p>The small GTPases Cdc42, Rac and RhoA have important regulatory roles in mediating cytoskeletal rearrangements, MAP kinase cascades and induction of G1 cell cycle progression. The activity of the GTPases is regulated by guanine nucleotide exchange factors (GEFs) which accelerate their GDP/GTP exchange rate, and thereby activate them. All the GEFs for the Rho-GTPases family share two conserved domains: the DH domain (for Dbl-homology domain) responsible for the enzymatic activity, and the PH domain, probably responsible for the proper localization of the molecule. Trio is a multifunctional protein that is comprised of two functional Rho-GEFs domains and a serine/threonine kinase domain. We have shown in vitro and in vivo that the first GEF domain (GEFD1) activates Rac1, while the second GEF domain (GEFD2) acts on RhoA. Moreover, the co-expression of both domains induces simultaneously the activation of both GTPases. To our knowledge, this is the first example of a member of the Rho-GEF family, that contains two functional exchange factor domains, with restricted and different specificity. We are currently investigating how these GEF domains are activated, by addressing the role of the PH domains in GTPases activation by Trio. We have shown that: 1) the PH1 of Trio is necessary for Rac activation by the GEFD1; 2) the PH1 of Trio targets the molecule to the cytoskeleton; 3) the GEFD1 domain of Trio binds, in a two-hybrid screen, the actin binding protein filamin. These data suggest that the PH1 targets Trio to the cytoskeleton close to Rac and its effectors, probably via interaction with the actin-binding protein filamin, consistent with a role of Trio in actin cytoskeleton remodeling.</p>","PeriodicalId":10658,"journal":{"name":"Comptes rendus des seances de la Societe de biologie et de ses filiales","volume":"192 2","pages":"367-74"},"PeriodicalIF":0.0000,"publicationDate":"1998-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Comptes rendus des seances de la Societe de biologie et de ses filiales","FirstCategoryId":"1085","ListUrlMain":"","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0

Abstract

The small GTPases Cdc42, Rac and RhoA have important regulatory roles in mediating cytoskeletal rearrangements, MAP kinase cascades and induction of G1 cell cycle progression. The activity of the GTPases is regulated by guanine nucleotide exchange factors (GEFs) which accelerate their GDP/GTP exchange rate, and thereby activate them. All the GEFs for the Rho-GTPases family share two conserved domains: the DH domain (for Dbl-homology domain) responsible for the enzymatic activity, and the PH domain, probably responsible for the proper localization of the molecule. Trio is a multifunctional protein that is comprised of two functional Rho-GEFs domains and a serine/threonine kinase domain. We have shown in vitro and in vivo that the first GEF domain (GEFD1) activates Rac1, while the second GEF domain (GEFD2) acts on RhoA. Moreover, the co-expression of both domains induces simultaneously the activation of both GTPases. To our knowledge, this is the first example of a member of the Rho-GEF family, that contains two functional exchange factor domains, with restricted and different specificity. We are currently investigating how these GEF domains are activated, by addressing the role of the PH domains in GTPases activation by Trio. We have shown that: 1) the PH1 of Trio is necessary for Rac activation by the GEFD1; 2) the PH1 of Trio targets the molecule to the cytoskeleton; 3) the GEFD1 domain of Trio binds, in a two-hybrid screen, the actin binding protein filamin. These data suggest that the PH1 targets Trio to the cytoskeleton close to Rac and its effectors, probably via interaction with the actin-binding protein filamin, consistent with a role of Trio in actin cytoskeleton remodeling.

分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
[多功能Trio蛋白在控制Rac1和RhoA gtpase信号通路中的作用]。
小gtpase Cdc42, Rac和RhoA在介导细胞骨架重排,MAP激酶级联和诱导G1细胞周期进程中具有重要的调节作用。GTP酶的活性受鸟嘌呤核苷酸交换因子(gef)的调控,gef加速GTP /GTP的交换速率,从而激活GTP酶。Rho-GTPases家族的所有gef共享两个保守结构域:DH结构域(dbl同源结构域)负责酶活性,PH结构域可能负责分子的适当定位。Trio是一种多功能蛋白,由两个功能性Rho-GEFs结构域和一个丝氨酸/苏氨酸激酶结构域组成。我们已经在体外和体内证明了第一个GEF结构域(GEFD1)激活Rac1,而第二个GEF结构域(GEFD2)作用于RhoA。此外,这两个结构域的共表达可同时诱导两种gtpase的激活。据我们所知,这是Rho-GEF家族成员的第一个例子,它包含两个功能交换因子结构域,具有有限的和不同的特异性。我们目前正在研究这些GEF结构域是如何被激活的,通过Trio研究PH结构域在GTPases激活中的作用。我们已经证明:1)Trio的PH1是GEFD1激活Rac所必需的;2) Trio的PH1将分子靶向到细胞骨架上;3)在双杂交筛选中,Trio的GEFD1结构域与肌动蛋白结合蛋白丝蛋白结合。这些数据表明,PH1可能通过与肌动蛋白结合蛋白丝蛋白的相互作用,将Trio靶向到靠近Rac及其效应物的细胞骨架上,这与Trio在肌动蛋白细胞骨架重塑中的作用一致。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 去求助
来源期刊
自引率
0.00%
发文量
0
期刊最新文献
[Glycosaminoglycans and proteoglycans]. [Tissue selectivity of calcium channel blockers]. [Physiopathology of calcium channels: identification of calcium channelopathies]. [Intracellular calcium channels, hormone receptors and intercellular calcium waves]. [Astrocytes and lentivirus infection in an experimental models of macaque infected with SIVmac251].
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1