PLEKHG2/FLJ00018, a Rho family-specific guanine nucleotide exchange factor, is tyrosine phosphorylated via the EphB2/cSrc signaling pathway.
PLEKHG2/FLJ00018, a Rho family-specific guanine nucleotide exchange factor, is tyrosine phosphorylated via the EphB2/cSrc signaling pathway.
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DOI：
10.1016/j.cellsig.2013.12.006
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发表时间：
2014-04
影响因子：
4.8
通讯作者：
Katsuya Sato;Takahiro Suzuki;Y. Yamaguchi;Y. Kitade;T. Nagase;H. Ueda
中科院分区：
文献类型：
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作者：
Katsuya Sato;Takahiro Suzuki;Y. Yamaguchi;Y. Kitade;T. Nagase;H. Ueda
PLEKHG2/FLJ00018 是一种 Rho 家族特异性鸟嘌呤核苷酸交换因子 (RhoGEF)，由异源三聚体 GTP 结合蛋白（G 蛋白）Gβγ 亚基激活，进而激活小 G 蛋白 Rac 和 Cdc42，这两种蛋白已被证明可以介导导致肌动蛋白细胞骨架重组的信号通路。在本研究中，我们发现，在 HEK293 细胞中，cSrc（一种非受体酪氨酸激酶）的组成型活性突变体和 PLEKHG2 的共表达诱导了 PLEKHG2 的酪氨酸磷酸化。通过缺失和碱基替换诱变，我们确定了 PLEKHG2 的 Tyr489 是 cSrc 磷酸化的位点。此外，使用高通量 src 同源 2 (SH2) 结构域结合测定，ABL1 的 SH2 结构域和 PI 3 激酶调节亚基 (PIK3R3) 被确定为酪氨酸磷酸化 PLEKHG2 的结合配偶体的候选者。 PLEKHG2 与全长 PIK3R3（而非 ABL1）之间的相互作用以酪氨酸磷酸化依赖性方式发生。此外，PLEKHG2 在 Tyr489 处被 ephrinB2 受体信号通过 cSrc 磷酸化。 PLEKHG2 中 Tyr489 酪氨酸磷酸化生理功能的研究仍然是未来研究的主题。
PLEKHG2/FLJ00018, a Rho family-specific guanine nucleotide exchange factor (RhoGEF), is activated by heterotrimeric GTP-binding protein (G protein) Gβγ subunits, and in turn activates the small G protein Rac and Cdc42, which have been shown to mediate signaling pathways leading to actin cytoskeletal reorganization. In the present study, we show that co-expression of the constitutively active mutant of cSrc, a non-receptor tyrosine kinase, and PLEKHG2 induced the tyrosine phosphorylation of PLEKHG2 in HEK293 cells. Through deletion and base substitution mutagenesis we have identified Tyr489 of PLEKHG2 as the site phosphorylated by cSrc. Furthermore, using a high-throughput src homology 2 (SH2) domain binding assay, the SH2 domain of ABL1 and the PI 3-kinse regulator subunit (PIK3R3) were identified as candidates for the binding partner of tyrosine-phosphorylated PLEKHG2. The interaction between PLEKHG2 and the full-length of PIK3R3, but not ABL1, occurs in a tyrosine-phosphorylation-dependent manner. Furthermore, PLEKHG2 is tyrosine phosphorylated at Tyr489 by ephrinB2 receptor signaling via cSrc. Investigation of the physiological function of tyrosine phosphorylation at Tyr489 in PLEKHG2 remains a subject for future studies.