| First Author | Matsui T | Year | 2002 |
| Journal | EMBO J | Volume | 21 |
| Issue | 5 | Pages | 1021-30 |
| PubMed ID | 11867530 | Mgi Jnum | J:115358 |
| Mgi Id | MGI:3691495 | Doi | 10.1093/emboj/21.5.1021 |
| Citation | Matsui T, et al. (2002) K-Ras mediates cytokine-induced formation of E-cadherin-based adherens junctions during liver development. EMBO J 21(5):1021-30 |
| abstractText | The E-cadherin-based adherens junction (AJ) is essential for organogenesis of epithelial tissues including the liver, although the regulatory mechanism of AJ formation during development remains unknown. Using a primary culture system of fetal hepatocytes in which oncostatin M (OSM) induces differentiation, we show here that OSM induces AJ formation by altering the subcellular localization of AJ components including E-cadherin and catenins. By retroviral expression of dominant-negative forms of signaling molecules, Ras was shown to be required for the OSM-induced AJ formation. Fetal hepatocytes derived from K-Ras knockout (K-Ras-/-) mice failed to form AJs in response to OSM, whereas AJ formation was induced normally by OSM in mutant hepatocytes lacking both H-Ras and N-Ras. Moreover, the defective phenotype of K-Ras-/- hepatocytes was restored by expression of K-Ras, but not by H-Ras and N-Ras. Finally, pull-down assays using the Ras-binding domain of Raf1 demonstrated that OSM directly activates K-Ras in fetal hepatocytes. These results indicate that K-Ras specifically mediates cytokine signaling for formation of AJs during liver development. |
