Role of interleukin (IL)-2 receptor beta-chain subdomains and Shc in p38 mitogen-activated protein (MAP) kinase and p54 MAP kinase (stress-activated protein Kinase/c-Jun N-terminal kinase) activation. IL-2-driven proliferation is independent of p38 and p54 MAP kinase activation
| Autor: | A E, Hunt, F V, Lali, J D, Lord, B H, Nelson, T, Miyazaki, K J, Tracey, B M, Foxwell |
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| Rok vydání: | 1999 |
| Předmět: |
Pyridines
T-Lymphocytes Hydrazones Imidazoles Receptors Interleukin-2 Protein Serine-Threonine Kinases p38 Mitogen-Activated Protein Kinases Cell Line Enzyme Activation Mice Calcium-Calmodulin-Dependent Protein Kinases Animals Interleukin-2 Mitogen-Activated Protein Kinase 9 Enzyme Inhibitors Mitogen-Activated Protein Kinases Protein Kinase Inhibitors Protein Kinases Cell Division |
| Zdroj: | The Journal of biological chemistry. 274(11) |
| ISSN: | 0021-9258 |
| Popis: | We have shown recently that interleukin (IL)-2 activates the mitogen-activated protein (MAP) kinase family members p38 (HOG1/stress-activated protein kinase II) and p54 (c-Jun N-terminal kinase/stress-activated protein kinase I). Furthermore, the p38 MAP kinase inhibitor SB203580 inhibited IL-2-driven T cell proliferation, suggesting that p38 MAP kinase might be involved in mediating proliferative signals. In this study, using transfected BA/F3 cell lines, it is shown that both the acidic domain and the membrane-proximal serine-rich region of the IL-2Rbeta chain are required for p38 and p54 MAP kinase activation and that, as for p42/44 MAP kinase, this activation requires the Tyr338 residue of the acidic domain, the binding site for Shc. It is well established that the acidic domain of the IL-2Rbeta chain is dispensable for IL-2-driven proliferation, and thus our observations suggest that neither p38 nor p54 MAP kinase activation is required for IL-2-driven proliferation of BA/F3 cells. In addition, the tetravalent guanylhydrazone inhibitor of proinflammatory cytokine production, CNI-1493, can block the activation of p54 and p38 MAP kinases by IL-2 but has no effect on IL-2-driven proliferation of BA/F3 cells, activated primary T cells, or a cytotoxic T cell line. Furthermore, our observations provide evidence for the existence of an additional, unknown target of the p38 MAP kinase inhibitor SB203580, the activation of which is essential for mitogenic signaling by IL-2. |
| Databáze: | OpenAIRE |
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