Identification of novel Gβγ dependent RhoGEF interacting molecules

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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.