| First Author | Yamamoto K | Year | 2002 |
| Journal | Biochem Biophys Res Commun | Volume | 297 |
| Issue | 5 | Pages | 1245-52 |
| PubMed ID | 12372421 | Mgi Jnum | J:239213 |
| Mgi Id | MGI:5825437 | Doi | 10.1016/s0006-291x(02)02378-1 |
| Citation | Yamamoto K, et al. (2002) The human perforin gene is a direct target of STAT4 activated by IL-12 in NK cells. Biochem Biophys Res Commun 297(5):1245-52 |
| abstractText | IL-12 activates STAT4 by inducing tyrosine phosphorylation, homo-dimerization, and nuclear translocation in NK cells and thereby stimulates proliferation and activation of these cells. The pore-forming protein perforin is a key effector protein for NK cell- and cytotoxic T lymphocyte-mediated cytolysis. Here we demonstrate that IL-12 induces the expression of the perforin gene in human NK cell line, NKL. Electrophoretic mobility shift assays using a probe containing two putative STAT-binding sequences located at -1085 and -1059 in the human perforin gene showed that STAT4 or STAT5 activated by IL-12 or IL-2, respectively, in NKL cells binds this region. Further analyses using various probes with or without mutated STAT-binding sequences showed that, although either of the two tandem STAT-binding sequences binds STAT4 weakly, the presence of both is required for significant binding of activated STAT4 and for formation of the STAT4-DNA-binding complex with lower electrophoretic mobility. Furthermore, mutation of either of the tandem STAT-binding sequences abolished the IL-12-induced activation of the perforin gene promoter in reporter gene assays. These results indicate that the IL-12-induced expression of the perforin gene in NK cells is directly regulated by STAT4, which binds, most likely as a homo-tetramer, to the tandem STAT-binding sequences in the perforin gene promoter. |
