Identification of a Rho family specific guanine nucleotide exchange factor, FLJ00018, as a novel actin-binding protein

• Published in: Cellular signalling 2013-01, Vol.25 (1), p.41-49
• Main Authors: Sato, Katsuya, Handa, Hiroaki, Kimura, Masashi, Okano, Yukio, Nagaoka, Hitoshi, Nagase, Takahiro, Sugiyama, Tsuyoshi, Kitade, Yukio, Ueda, Hiroshi
• Format: Article
• Language: English
• Subjects: Actin; Actins - genetics; Actins - metabolism; Animals; FLJ00018; G protein; Gene transcription; GTP-Binding Protein beta Subunits - genetics; GTP-Binding Protein beta Subunits - metabolism; GTP-Binding Protein gamma Subunits - genetics; GTP-Binding Protein gamma Subunits - metabolism; Guanine Nucleotide Exchange Factors - chemistry; Guanine Nucleotide Exchange Factors - genetics; Guanine Nucleotide Exchange Factors - metabolism; HEK293 Cells; Humans; Mice; NIH 3T3 Cells; Protein Binding; Protein Structure, Tertiary; Rho; RhoGEF; Serum Response Element; Transcription, Genetic; Transfection; Two-Hybrid System Techniques
• ISSN: 0898-6568; 1873-3913
• DOI: 10.1016/j.cellsig.2012.09.015

FLJ00018/PLEKHG2 is a guanine nucleotide exchange factor for the Rho family small GTPases. FLJ00018 is directly activated by heterotrimeric G protein Gβγ subunits. Using two-hybrid screening, we have identified non-muscle cytosolic actin as a binding partner of FLJ00018. We found that there were two actin-binding regions in FLJ00018 at the N-terminal region (150–283 amino acids) and at the C-terminal region (465–1386 amino acids). The overexpression of non-muscle cytosolic actin attenuated the FLJ00018-induced serum response element-dependent gene transcription. These results suggest that non-muscle cytosolic actin may be a negative regulator of FLJ00018 through its interaction with the Dbl homology domain. [Display omitted] ► Gβγ-dependent RhoEGF, FLJ00018, interacts with non-muscle actin. ► It is thought that FLJ00018 has more than two actin-binding regions in FLJ00018. ► One of actin-binding regions is at 150–283 amino acids of FLJ00018. ► The interaction of actin attenuates FLJ00018-induced SRE-dependent gene transcription.