Identification of novel Gβγ dependent RhoGEF interacting molecules

Dbl家族的鸟嘌呤核苷酸交换因子（guanine nucleotide exchange factors）通过激活Rho家族的GTP酶来调节细胞骨架的排列、信号转导和基因表达等多种细胞事件。FLJ 00018/CLG/PLEKHG 2是Rho家族小GTP酶和Dbl同源（DH）、Pleckstrin同源（PH）结构域的鸟嘌呤核苷酸交换因子（GEF）。FLJ 00018具有与异源三聚体GTP结合蛋白βγ亚基结合的区域。这种相互作用激活FLJ 00018的GEF活性，从而增强血清反应元件（SRE）依赖性基因转录并影响细胞铺展。在这个研究项目中，我们研究了FLJ 00018的PH结构域的功能意义。我们发现FLJ 00018的PH结构域与含有PtdIns（4，5）P2、PtdIns（3，4，5）P3和磷脂酸的磷酸肌醇相互作用。磷脂酶C和磷脂酶D通过PH结构域调节FLJ 00018功能。

Rho family GTPase-specific guanine nucleotide exchange factors of Dbl family regulate avariety of cellular events including cytoskeletal arrangement, signal transduction, and gene expression through activation of Rho family GTPases. FLJ00018/CLG/PLEKHG2 is a guanine nucleotide exchange factor (GEF) for Rho family of small GTPases and Dbl homology (DH), Pleckstrin homology (PH) domains. FLJ00018 possesses a region that binds to heterotrimeric GTP-binding protein βγ subunits. This interaction activates the GEF activity of FLJ00018, and thereby enhances serum response element (SRE) dependent gene transcription and affects cell spreading. In this research project, we have examined the functional significance of the PH domain of FLJ00018. We show here that the PH domain of FLJ00018 interact to phosphoinositide containing PtdIns(4,5)P2, PtdIns(3,4,5)P3 and phosphatidic acid. Phosopholipase C and phospholipase D regulate FLJ00018 functions through the PH domain.