title: The inositol 5-phosphatase SHIP2 is an effector of RhoA and is involved in cell polarity and migration.
abstract: 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.
authors.affiliation: Department of Cell Pharmacology, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Kato
authors.forename: Tsubasa
authors.initials: T
authors.lastname: Yazawa
authors.forename: Kentaro
authors.initials: K
authors.lastname: Taki
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Mori
authors.forename: Shujie
authors.initials: S
authors.lastname: Wang
authors.forename: Tomoki
authors.initials: T
authors.lastname: Nishioka
authors.forename: Tomonari
authors.initials: T
authors.lastname: Hamaguchi
authors.forename: Toshiki
authors.initials: T
authors.lastname: Itoh
authors.forename: Tadaomi
authors.initials: T
authors.lastname: Takenawa
authors.forename: Chikako
authors.initials: C
authors.lastname: Kataoka
authors.forename: Yoshiharu
authors.initials: Y
authors.lastname: Matsuura
authors.forename: Mutsuki
authors.initials: M
authors.lastname: Amano
authors.forename: Toyoaki
authors.initials: T
authors.lastname: Murohara
authors.forename: Kozo
authors.initials: K
authors.lastname: Kaibuchi
mesh_terms: D000818:Animals; D002465:Cell Movement; D016764:Cell Polarity; D002478:Cells, Cultured; D002846:Chromatography, Affinity; D006801:Humans; D051379:Mice; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases; D010744:Phosphoric Monoester Hydrolases / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D025941:Protein Interaction Mapping; D051381:Rats; D015398:Signal Transduction; D020742:rhoA GTP-Binding Protein / Q000737:chemistry / Q000378:metabolism*
chemical_list: C066737:RHOA protein, human; D010744:Phosphoric Monoester Hydrolases; C098706:INPPL1 protein, human; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases; D020742:rhoA GTP-Binding Protein