The Rho guanine nucleotide exchange factor PLEKHG1 is activated by interaction with and phosphorylation by Src family kinase member FYN.
The Rho guanine nucleotide exchange factor PLEKHG1 is activated by interaction with and phosphorylation by Src family kinase member FYN.
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DOI：
10.1016/j.jbc.2022.101579
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发表时间：
2022-03
期刊：
影响因子：
--
通讯作者：
Ueda H
中科院分区：
文献类型：
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作者：
Nakano S;Nishikawa M;Kobayashi T;Harlin EW;Ito T;Sato K;Sugiyama T;Yamakawa H;Nagase T;Ueda H
Rho家族小分子GTP酶(Rho)通过时空调控肌动蛋白细胞骨架，调控多种细胞运动过程。一些Rho特异性的鸟嘌呤核苷酸交换因子(RhoGEF)由Src家族酪氨酸激酶(SFK)通过酪氨酸磷酸化来调节。我们以前也报道过PLEKHG2，一个GTPase rac1和CDc42的Rhogef，被SRC酪氨酸磷酸化。然而，SFK调控RhoGEF的机制细节还不是很清楚。在本研究中，我们首次发现与PLEKHG2的DBL和Pleckstrin同源结构域具有很高同源性的PLEKHG1被SFK家族成员FYN激活后激活CDC42。我们还表明，FYN对PLEKHG1的激活需要这两种蛋白之间的相互作用，以及FYN诱导的PLEKHG1的酪氨酸磷酸化。我们还发现，包含FYN的Src同源3和Src同源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的调节者，可能通过与PLEKHG1的相互作用和酪氨酸磷酸化而通过Rho信号调节细胞形态。
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.
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影响因子：
64.8
作者：
Jumper J;Evans R;Pritzel A;Green T;Figurnov M;Ronneberger O;Tunyasuvunakool K;Bates R;Žídek A;Potapenko A;Bridgland A;Meyer C;Kohl SAA;Ballard AJ;Cowie A;Romera-Paredes B;Nikolov S;Jain R;Adler J;Back T;Petersen S;Reiman D;Clancy E;Zielinski M;Steinegger M;Pacholska M;Berghammer T;Bodenstein S;Silver D;Vinyals O;Senior AW;Kavukcuoglu K;Kohli P;Hassabis D
通讯作者：
Hassabis D
影响因子：
4.8
作者：
Ren, Y;Li, R;Busch, H
通讯作者：
Busch, H
影响因子：
4.8
作者：
Liang, XQ;Lu, Y;Resh, MD
通讯作者：
Resh, MD
影响因子：
14.9
作者：
Obenauer, JC;Cantley, LC;Yaffe, MB
通讯作者：
Yaffe, MB
影响因子：
21.3
作者：
通讯作者：
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