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• W1971823806 abstract "AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Abstract IL-2 is the major regulatory cytokine of the immune system. It plays a key role in T cell survival, growth and activation. IL-2 may induce the expression of multiple genes including some cytokine genes. The induction of these genes is triggered by different signal pathways, one of them being the Jak-STAT signal pathway. The genes regulated by this pathway remain to be determined. By studying IL-2-inducible genes, we have confirmed that the TNF-β gene is one of the immediate early genes activated by IL-2. By analysis of the DNA sequences around 180 – 300 bases upstream of the transcription initiation point of the mouse TNF-β gene, we demonstrate that there is a STAT5 binding site which is essential to the inducibility of the TNF-β gene. Furthermore, in BA/F3 cells co-transfected with the STAT5A gene and IL-2Rβ gene, the activation of the TNF-β gene promoter by IL-2 was greatly promoted, whereas the TNF-β gene promoter became IL-2-non-inducible if the STAT5A gene was substituted with a dominant negative STAT5A, i.e. a C-terminally truncated mutant. Taken together, our results show that the Jak-STAT signal pathway is involved in induction of the TNF-β gene in cells stimulated by IL-2. References 1 Harak, I. D., Gress, R. E., Lucas, P. J., Horak, E. M., Waldmann, T. A. and Bolen, J. B., T-lymphocyte interleukin 2-dependent tyrosine protein kinase signal transduction involves the activation of p56lck. Proc. Natl. Acad. Sci. 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W., Cleveland, J. L., Yi, T. and Ihle, J. N., Structure of the murine JAK2 protein-tyrosine kinase and its role in interleukin 3 signal transduction. Proc. Natl. Acad. Sci. USA 1993. 90: 8429– 8433. 7 Witthuhn, B., Quelle, F. W., Silvennoinen, O., Yi, T., Tang, B., Miura, O. and Ihle, J. N., JAK2 associates with the erythropoietin receptor and is tyrosine phosphorylated and activated following stimulation with erythropoietin. Cell 1993. 74: 227– 236. 8 Gusehin, D., Rogers, N., Briscoe, J., Witthuhn, B., Watling, D., Horn, F., Pellegrini, S., Yasukawa, K., Heinrich, P., Stark, G. R., Ihle, J. N. and Kerr, I. M., A major role for the protein tyrosine kinase JAK1 in the JAK/STAT signal transduction way in response to interleukin-6. EMBO J. 1995. 14: 1421– 1429. 9 Akira, S., Nishio, Y., Inoue, M., Wang, X. J., Wei, S., Matsusaka, T., Yoshida, K., Sudo, T., Naruto, M. and Kishimoto, T., Molecular cloning of APRF, a novel IFN- stimulated gene factor 3 p91 -related transcription factor involved in the gp130-mediated signaling pathway. Cell 1994. 77: 63– 71. 10 Wakao, H., Harada, N., Kitamura, T., Mui, A. L. and Miyajma, A., Interleukin 2 and erythropoietin activate STAT5/MGF distinct pathways. EMBO J. 1995. 14: 2527– 2535. 11 Azam, M., Erdjument-Bromage, H., Kreider, B. L., Xia, M., Quelle, F., Basu, R., Saris, C., Tempst, P., Ihle, J. N. and Schindler, C., Interleukin-3 signals through multiple informs of STAT5. EMBO J. 1995. 14: 1402– 1411. 12 Mui, A. L., Wakao, H., O'Farell, A. M., Harad, N. and Mryajima, A., Interleukin-3, granulocyte-macrophage colony stimulating factor and interleukin-5 transduce signals through two STAT5 homologs. EMBO J. 1995. 14: 1166– 1175. 13 Diatchenko, L., Lau, Y.-F. C., Campbell, A. 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A., Mashuhara, M., Yokouchi, M., Suzuki, R., Sakamoto, H., Mitsui, K., Matsumoto, A., Tanimura, S., Ohtsubo, M., Misawa, H., Taniguchi, T., Fujita, T., Kanakura, Y., Komiya, S. and Yoshimura, A., A new protein containing an SH2 domain that inhibits JAK kinases. Nature 1997. 387: 921– 924. 17 Mui, A. L., Wakao, H., Kinoshita, T., Kitamura, T. and Miyajima, A., Suppression of lnterleukin-3-induced gene expression by c-terminal truncated stat5: role of stat5 in proliferation. EMBO J. 1996. 15: 2425– 2433. 18 Pauli, U., Control of tumor necrosis factor gene expression. Crit. Rev. Eukaryot. Gene Expr. 1994. 4: 323– 344. 19 Weil, D., Brosset, S. and Dautry, F., RNA processing is a limiting step for murine tumor necrosis factor beta expression in response to interleukin-2. Mol. Cell Biol. 1990. 10: 5865– 5875. 20 Melkonyan, H., Sorg, C. and Klempt, M., Electroporation efficiency in mammalian cells is increased by dimethylsulfoxide (DMSO). Nucleic Acids Res. 1996. 24: 4356– 4357. 21 J. Sambrook, E. F. Fritsch and T. Maniatis (Eds.) , Molecular Cloning: A Laboratory Manual. Cold Spring Harbor Laboratory Press, Cold Spring Harbor 1989. 22 Andrews, N. C. and Faller, D. V., A rapid micropreparation technique for extraction of DNA binding proteins from limiting numbers of mammalian cells. Nucleic Acids Res. 1991. 19: 2499. Citing Literature Volume28, Issue3March 1998Pages 805-810 ReferencesRelatedInformation" @default.
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