title: Tyrosine Phosphorylation of SGEF Regulates RhoG Activity and Cell Migration.
abstract: SGEF and Ephexin4 are members of the Ephexin subfamily of RhoGEFs that specifically activate the small GTPase RhoG. It is reported that Ephexin1 and Ephexin5, two well-characterized Ephexin subfamily RhoGEFs, are tyrosine-phosphorylated by Src, and that their phosphorylation affect their activities and functions. In this study, we show that SGEF, but not Ephexin4, is tyrosine-phosphorylated by Src. Tyrosine phosphorylation of SGEF suppresses its interaction with RhoG, the elevation of RhoG activity, and SGEF-mediated promotion of cell migration. We identified tyrosine 530 (Y530), which is located within the Dbl homology domain, as a major phosphorylation site of SGEF by Src, and Y530F mutation blocked the inhibitory effect of Src on SGEF. Taken together, these results suggest that the activity of SGEF is negatively regulated by tyrosine phosphorylation of the DH domain.
authors.affiliation: Laboratory of Molecular Neurobiology, Graduate School of Pharmaceutical Sciences, Kyoto University, Yoshidakonoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Okuyama
authors.affiliation: Laboratory of Molecular Neurobiology, Graduate School of Pharmaceutical Sciences, Kyoto University, Yoshidakonoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Umeda
authors.affiliation: Laboratory of Molecular Neurobiology, Graduate School of Pharmaceutical Sciences, Kyoto University, Yoshidakonoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.|Laboratory of Molecular Neurobiology, Graduate School of Biostudies, Kyoto University, Yoshidakonoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Negishi
authors.affiliation: Laboratory of Molecular Neurobiology, Graduate School of Pharmaceutical Sciences, Kyoto University, Yoshidakonoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.|Laboratory of Molecular Neurobiology, Graduate School of Biostudies, Kyoto University, Yoshidakonoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Hironori
authors.initials: H
authors.lastname: Katoh
mesh_terms: D002465:Cell Movement / Q000235:genetics*; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics*; D057809:HEK293 Cells; D006801:Humans; D010766:Phosphorylation; D011485:Protein Binding; D014443:Tyrosine / Q000235:genetics; D020741:rho GTP-Binding Proteins / Q000235:genetics*; D018909:src Homology Domains / Q000235:genetics; D019061:src-Family Kinases / Q000235:genetics*
chemical_list: C556035:ARHGEF16 protein, human; C473930:ARHGEF26 protein, human; D020662:Guanine Nucleotide Exchange Factors; C075397:RHOG protein, human; D014443:Tyrosine; D019061:src-Family Kinases; D020741:rho GTP-Binding Proteins