The inositol 5-phosphatase SHIP2 is an effector of RhoA and is involved in cell polarity and migration

Department of Cell Pharmacology, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.
Molecular biology of the cell (Impact Factor: 4.47). 05/2012; 23(13):2593-604. DOI: 10.1091/mbc.E11-11-0958
Source: PubMed


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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Available from: Kozo Kaibuchi, Mar 05, 2014
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    • "RhoA belongs to the small molecule G protein superfamily, which is widely expressed in different types of cells and tissues. With a variety of biological functions, RhoA plays an important role in the regulation of the actin cytoskeleton, which is mainly involved in the reorganization of the cytoskeleton, cell migration and adhesion, cell polarization and activation and DNA transcription, as well as other functions (30,31). In the reproductive field, Melendez et al found that RhoA was essential in mouse embryonic fibroblastic mitosis (9). "
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