Nishikawa Masashi, Sato Katsuya, Nakano Shun, Yamakawa Hisashi, Nagase Takahiro, Ueda Hiroshi
a United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University , Yanagido, Gifu , Japan.
b Department of Molecular Pathobiochemistry, Gifu University Graduate School of Medicine , Yanagido, Gifu , Japan.
Small GTPases. 2019 Sep;10(5):361-366. doi: 10.1080/21541248.2017.1327838. Epub 2017 Jun 19.
PLEKHG2 is a Gβγ- and Gαs-dependent guanine nucleotide exchange factor for Rac1 and Cdc42 small GTPases and has been shown to mediate signaling pathways such as those for actin cytoskeletal reorganization and serum response element (SRE)-dependent gene transcription. We have shown that the four-and-a-half LIM domains (FHL) 1 acts as a positive regulator of PLEKHG2. Here, we evaluated the other FHL family members and found that the FHL1A specifically regulate the PLEKHG2 activity. Moreover, FHL1A further enhanced Gβγ- and PLEKHG2-induced SRE-dependent gene transcription, whereas FHL1A partially restored the attenuated PLEKHG2-induced SRE-dependent gene transcription by Gαs. Our results suggest that FHL1A specifically interacts with PLEKHG2 to regulate a function of PLEKHG2 that is modified by the interaction of Gβγ and Gαs.
PLEKHG2是一种依赖Gβγ和Gαs的Rac1和Cdc42小GTP酶的鸟嘌呤核苷酸交换因子，已被证明可介导诸如肌动蛋白细胞骨架重组和血清反应元件（SRE）依赖性基因转录等信号通路。我们已经表明，四半LIM结构域（FHL）1作为PLEKHG2的正调节因子发挥作用。在此，我们评估了其他FHL家族成员，发现FHL1A特异性调节PLEKHG2活性。此外，FHL1A进一步增强了Gβγ和PLEKHG2诱导的SRE依赖性基因转录，而FHL1A部分恢复了Gαs减弱的PLEKHG2诱导的SRE依赖性基因转录。我们的结果表明，FHL1A与PLEKHG2特异性相互作用，以调节由Gβγ和Gαs相互作用修饰的PLEKHG2的功能。
