Activation of Rac1 by Rho-guanine nucleotide dissociation inhibitor-β with defective isoprenyl-binding pocket
Activation of Rac1 by Rho-guanine nucleotide dissociation inhibitor-β with defective isoprenyl-binding pocket
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DOI：
10.1016/j.cellbi.2006.09.002
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发表时间：
2007-01-01
影响因子：
3.9
通讯作者：
Tatsuka, Masaaki
中科院分区：
文献类型：
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作者：
Ota, Takahide;Maeda, Masayo;Tatsuka, Masaaki
Rho-鸟嘌呤核苷酸解离通道-P（RhoGDI β）是Rho GTP酶的调节剂，与癌细胞进展有关。我们报道了C-末端截短的RhoGDI β（Delta C（166-201）-RhoGD β）通过激活Ras转化的成纤维细胞中的Rac 1信号通路促进转移。为了更好地理解转移过程中Delta C（166-201）-RhoGDI β激活Rac 1的机制，将GTP结合的Rac 1的量测量为表达具有连续C末端缺失的各种突变RhoGDI β的细胞中Rac 1的激活水平。三个C-末端疏水氨基酸残基（Trp 191，Leu 193和Ile 195）应该与Rac 1的异戊二烯基相互作用，是Rac 1激活/抑制的适当调节所必需的。该区域的缺失导致RhoGDI β持续与GTP结合的Rac 1结合，引起Rac 1的组成性激活。因此，RhoGDI β与Rac 1异戊二烯基的相互作用受损可能使RhoGDI β在转移过程中作为Rac 1的正调节剂发挥作用。(c)2006年国际细胞生物学联合会。由爱思唯尔有限公司出版。保留所有权利。
Rho-guanine nucleotide dissociation inhibitor-P (RhoGDI beta), a regulator for Rho GTPases, is implicated in cancer cell progression. We reported that C-terminal truncated RhoGDI beta (Delta C(166-201)-RhoGD beta) promoted metastasis through activating Rac1 signaling pathway in ras-transformed fibroblast cells. To better understand the mechanism of Rac1 activation by Delta C(166-201)-RhoGDI beta during metastasis, the amount of GTP-bound Rac1 was measured as the activation level of Rac1 in cells expressing various mutant RhoGDI beta with sequential C-terminal deletions. Three C-terminal hydrophobic amino acid residues (Trp191, Leu193, and Ile195) supposed to interact with isoprenyl groups of Rac1, was indispensable for a proper regulation of Rac1 activation/inhibition. Deletion of this region led RhoGDI beta to continuously associate with GTP-bound Rac1, provoking constitutive activation of Rac1. Thus, impaired interaction of RhoGDI beta with Rac1 isoprenyl groups possibly makes RhoGDI beta function as a positive regulator for Rac1 during metastasis. (c) 2006 International Federation for Cell Biology. Published by Elsevier Ltd. All rights reserved.