Regulation of lymphotoxin production by the p21ras-raf-MEK-ERK cascade in PHA/PMA-stimulated Jurkat cells
| Autor: | Y Q, Li, C S, Hii, M, Costabile, D, Goh, C J, Der, A, Ferrante |
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| Rok vydání: | 1999 |
| Předmět: |
Mitogen-Activated Protein Kinase Kinases
Molecular Sequence Data MAP Kinase Kinase 1 Protein Serine-Threonine Kinases Protein-Tyrosine Kinases Enzyme Activation Proto-Oncogene Proteins c-raf Proto-Oncogene Proteins p21(ras) Jurkat Cells Calcium-Calmodulin-Dependent Protein Kinases Humans Tetradecanoylphorbol Acetate Amino Acid Sequence Phytohemagglutinins Lymphotoxin-alpha Cell Division |
| Zdroj: | Journal of immunology (Baltimore, Md. : 1950). 162(6) |
| ISSN: | 0022-1767 |
| Popis: | Although the production of lymphotoxin (LT) from activated Th1 lymphocytes has been reported extensively, the intracellular signaling mechanisms that regulate this T cell function remain totally undefined. We have examined whether the p21ras-raf-1-mitogen-activated protein kinase/extracellular signal-regulated protein kinase (ERK) kinase (MEK)-ERK cascade plays a role in regulating the production of LT, because the activity of these signaling molecules is up-regulated in activated T lymphocytes. Transfection of Jurkat leukemic T cells with a dominant negative mutant of p21ras (ras17N or ras15A), raf-1 (raf 1-130), or ERK1 (Erk1-K71R) resulted in the suppression of the mitogen/phorbol ester-stimulated production/secretion of LT. This suppression was accompanied by a parallel inhibition of mitogen-stimulated ERK activation. The selective antagonist of MEK1 activation, PD98059, also attenuated the mitogen-stimulated or anti-CD3 Ab and phorbol ester-stimulated production of LT from Jurkat cells or peripheral blood T lymphocytes. This study provides, for the first time, direct evidence that the p21ras-raf-MEK-ERK cascade plays a vital role in regulating the production of LT. |
| Databáze: | OpenAIRE |
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