| First Author | Wan Q | Year | 2013 |
| Journal | Biochem Biophys Res Commun | Volume | 433 |
| Issue | 4 | Pages | 502-7 |
| PubMed ID | 23524265 | Mgi Jnum | J:201218 |
| Mgi Id | MGI:5512803 | Doi | 10.1016/j.bbrc.2013.03.020 |
| Citation | Wan Q, et al. (2013) Rac1 and Cdc42 GTPases regulate shear stress-driven beta-catenin signaling in osteoblasts. Biochem Biophys Res Commun 433(4):502-7 |
| abstractText | Beta-catenin-dependent TCF/LEF (T-cell factor/lymphocyte enhancing factor) is known to be mechanosensitive and an important regulator for promoting bone formation. However, the functional connection between TCF/LEF activity and Rho family GTPases is not well understood in osteoblasts. Herein we investigated the molecular mechanisms underlying oscillatory shear stress-induced TCF/LEF activity in MC3T3-E1 osteoblast cells using live cell imaging. We employed fluorescence resonance energy transfer (FRET)-based and green fluorescent protein (GFP)-based biosensors, which allowed us to monitor signal transduction in living cells in real time. Oscillatory (1Hz) shear stress (10 dynes/cm2) increased TCF/LEF activity and stimulated translocation of beta-catenin to the nucleus with the distinct activity patterns of Rac1 and Cdc42. The shear stress-induced TCF/LEF activity was blocked by the inhibition of Rac1 and Cdc42 with their dominant negative mutants or selective drugs, but not by a dominant negative mutant of RhoA. In contrast, constitutively active Rac1 and Cdc42 mutants caused a significant enhancement of TCF/LEF activity. Moreover, activation of Rac1 and Cdc42 increased the basal level of TCF/LEF activity, while their inhibition decreased the basal level. Interestingly, disruption of cytoskeletal structures or inhibition of myosin activity did not significantly affect shear stress-induced TCF/LEF activity. Although Rac1 is reported to be involved in beta-catenin in cancer cells, the involvement of Cdc42 in beta-catenin signaling in osteoblasts has not been identified. Our findings in this study demonstrate that both Rac1 and Cdc42 GTPases are critical regulators in shear stress-driven beta-catenin signaling in osteoblasts. |
