Tyrosine Phosphorylation of SGEF Regulates RhoG Activity and Cell Migration

被引：8

作者：

Okuyama, Yusuke ^{[1
]}

Umeda, Kentaro ^{[1
]}

Negishi, Manabu ^{[1
,2
]}

Katoh, Hironori ^{[1
,2
]}

机构：

[1] Kyoto Univ, Grad Sch Pharmaceut Sci, Mol Neurobiol Lab, Sakyo Ku, Yoshidakonoe Cho, Kyoto 6068501, Japan

[2] Kyoto Univ, Grad Sch Biostudies, Mol Neurobiol Lab, Sakyo Ku, Yoshidakonoe Cho, Kyoto 6068501, Japan

来源：

PLOS ONE | 2016年 / 11卷 / 07期

关键词：

NUCLEOTIDE EXCHANGE FACTOR; SERINE; 897; PHOSPHORYLATION; SMALL GTPASE RHOG; APOPTOTIC CELLS; RAC1; ACTIVATION; EPHA2; ANOIKIS; COMPLEX; CANCER; MORPHOGENESIS;

D O I：

10.1371/journal.pone.0159617

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：13

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