Abstract：
Rho family small GTPases (Rho) regulate various cell motility processes by spatiotemporally controlling the actin cytoskeleton. Some Rho-specific guanine nucleotide exchange factors (RhoGEFs) are regulated via tyrosine phosphorylation by Src family tyrosine kinase (SFK). We also previously reported that PLEKHG2, a RhoGEF for the GTPases Rac1 and Cdc42, is tyrosine-phosphorylated by SRC. However, the details of the mechanisms by which SFK regulates RhoGEFs are not well understood. In this study, we found for the first time that PLEKHG1, which has very high homology to the Dbl and pleckstrin homology domains of PLEKHG2, activates Cdc42 following activation by FYN, a member of the SFK family. We also show that this activation of PLEKHG1 by FYN requires interaction between these two proteins and FYN-induced tyrosine phosphorylation of PLEKHG1. We also found that the region containing the Src homology 3 and Src homology 2 domains of FYN is required for this interaction. Finally, we demonstrated that tyrosine phosphorylation of Tyr-720 and Tyr-801 in PLEKHG1 is important for the activation of PLEKHG1. These results suggest that FYN is a regulator of PLEKHG1 and may regulate cell morphology through Rho signaling via the interaction with and tyrosine phosphorylation of PLEKHG1.
摘要：
Rho家族小GTP酶（Rho）通过时空控制肌动蛋白细胞骨架来调节各种细胞运动过程。一些Rho特异性鸟嘌呤核苷酸交换因子(RhoGEF)通过Src家族酪氨酸激酶(SFK)的酪氨酸磷酸化来调节。我们先前还报道了PLEKHG2，GTPasesRac1和Cdc42的RhoGEF，被SRC酪氨酸磷酸化。然而,关于SFK调节RhoGEF的机制的细节尚不清楚.在这项研究中,我们首次发现与PLEKHG2的Dbl和pleckstrin同源域具有很高同源性的PLEKHG1在FYN激活后激活Cdc42，SFK家族的一员.我们还表明，FYN对PLEKHG1的激活需要这两种蛋白质与FYN诱导的PLEKHG1酪氨酸磷酸化之间的相互作用。我们还发现FYN的含有Src同源性3和Src同源性2结构域的区域是这种相互作用所必需的。最后,我们证明了PLEKHG1中Tyr-720和Tyr-801的酪氨酸磷酸化对于PLEKHG1的激活是重要的。这些结果表明，FYN是PLEKHG1的调节因子，可能通过与PLEKHG1的相互作用和酪氨酸磷酸化通过Rho信号调节细胞形态。
