ERK1/2 phosphorylate GEF-H1 to enhance its guanine nucleotide exchange activity toward RhoA
ERK1/2 phosphorylate GEF-H1 to enhance its guanine nucleotide exchange activity toward RhoA
复制标题
DOI：
10.1016/j.bbrc.2008.01.066
复制
发表时间：
2008-03-28
影响因子：
3.1
通讯作者：
Kohno, Michiaki
中科院分区：
文献类型：
--
作者：
Fujishiro, Shuh-hei;Tammura, Susumu;Kohno, Michiaki
Rho GTP酶在许多细胞过程的调节中起重要作用。虽然各种鸟嘌呤核苷酸交换因子（GEF）参与Rho GTP酶的激活，但调节这种活性的确切机制仍不清楚。我们已经研究了ERK 1/2是否参与GEF-H1（一种针对RhoA的GEF）的磷酸化，以调节其活性。在具有组成性ERK 1/2活化的HT 1080细胞中，GEF-H1的表达678诱导其在Thr（678）处的磷酸化，这通过用ERK通路抑制剂PD 184352处理细胞而完全消除。用12-O-十四酰基-佛波醇-13-乙酸酯刺激HeLa S3细胞以ERK依赖的方式诱导GEF-H1的磷酸化。ERK 1/2介导的Thr（678）磷酸化增强GEF-H1对RhoA的鸟嘌呤核苷酸交换活性。这些结果表明，ERK途径，通过增强GEF-H1的活性，有助于激活RhoA调节肌动蛋白组装，诱导细胞反应，包括增殖和运动的必要事件。(c)2008年爱思唯尔公司All rights reserved.
Rho GTPases play an essential role in the regulation of many cellular processes. Although various guanine nucleotide exchange factors (GEFs) are involved in the activation of Rho GTPases, the precise mechanism regulating such activity remains unclear. We have examined whether ERK1/2 are involved in the phosphorylation of GEF-H1, a GEF toward RhoA, to modulate its activity. Expression 678 of GEF-H1 in HT1080 cells with constitutive ERK1/2 activation induced its phosphorylation at Thr(678), which was totally abolished by treating the cells with PD184352, an ERK pathway inhibitor. Stimulation of HeLa S3 cells with 12-O-tetradecanoyl-phorbol-13-acetate induced the phosphorylation of GEF-H1 in an ERK-dependent manner. ERK1/2-mediated Thr(678)-phosphorylation enhanced the guanine nucleotide exchange activity of GEF-H1 toward RhoA. These results suggest that the ERK pathway, by enhancing the GEF-H1 activity, contributes to the activation of RhoA to regulate the actin assembly, a necessary event for the induction of cellular responses including proliferation and motility. (c) 2008 Elsevier Inc. All rights reserved.