TY - JOUR
T1 - The inositol 5-phosphatase SHIP2 is an effector of RhoA and is involved in cell polarity and migration
AU - Kato, Katsuhiro
AU - Yazawa, Tsubasa
AU - Taki, Kentaro
AU - Mori, Kazutaka
AU - Wang, Shujie
AU - Nishioka, Tomoki
AU - Hamaguchi, Tomonari
AU - Itoh, Toshiki
AU - Takenawa, Tadaomi
AU - Kataoka, Chikako
AU - Matsuura, Yoshiharu
AU - Amano, Mutsuki
AU - Murohara, Toyoaki
AU - Kaibuchi, Kozo
PY - 2012/7/1
Y1 - 2012/7/1
N2 - Cell migration is essential for various physiological and pathological processes. Polarization in motile cells requires the coordination of several key signaling molecules, including RhoA small GTPases and phosphoinositides. Although RhoA participates in a front-rear polarization in migrating cells, little is known about the functional interaction between RhoA and lipid turnover. We find here that src-homology 2-containing inositol-5-phosphatase 2 (SHIP2) interacts with RhoA in a GTP-dependent manner. The association between SHIP2 and RhoA is observed in spreading and migrating U251 glioma cells. The depletion of SHIP2 attenuates cell polarization and migration, which is rescued by wild-type SHIP2 but not by a mutant defective in RhoA binding. In addition, the depletion of SHIP2 impairs the proper localization of phosphatidylinositol 3,4,5-trisphosphate, which is not restored by a mutant defective in RhoA binding. These results suggest that RhoA associates with SHIP2 to regulate cell polarization and migration.
AB - Cell migration is essential for various physiological and pathological processes. Polarization in motile cells requires the coordination of several key signaling molecules, including RhoA small GTPases and phosphoinositides. Although RhoA participates in a front-rear polarization in migrating cells, little is known about the functional interaction between RhoA and lipid turnover. We find here that src-homology 2-containing inositol-5-phosphatase 2 (SHIP2) interacts with RhoA in a GTP-dependent manner. The association between SHIP2 and RhoA is observed in spreading and migrating U251 glioma cells. The depletion of SHIP2 attenuates cell polarization and migration, which is rescued by wild-type SHIP2 but not by a mutant defective in RhoA binding. In addition, the depletion of SHIP2 impairs the proper localization of phosphatidylinositol 3,4,5-trisphosphate, which is not restored by a mutant defective in RhoA binding. These results suggest that RhoA associates with SHIP2 to regulate cell polarization and migration.
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U2 - 10.1091/mbc.E11-11-0958
DO - 10.1091/mbc.E11-11-0958
M3 - Article
C2 - 22593208
AN - SCOPUS:84863508973
SN - 1059-1524
VL - 23
SP - 2593
EP - 2604
JO - Molecular Biology of the Cell
JF - Molecular Biology of the Cell
IS - 13
ER -