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https://hdl.handle.net/2440/7505
Type: | Journal article |
Title: | Regulation of lymphotoxin production by the p21ras-raf-MEK-ERK cascade in PHA/PMA-stimulated Jurkat cells |
Author: | Li, Y. Hii, C. Costabile, M. Goh, D. Der, C. Ferrante, A. |
Citation: | Journal of Immunology, 1999; 162(6):3316-3320 |
Publisher: | AMER ASSOC IMMUNOLOGISTS |
Issue Date: | 1999 |
ISSN: | 0022-1767 1550-6606 |
Abstract: | 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. |
Keywords: | Jurkat Cells Humans Tetradecanoylphorbol Acetate Proto-Oncogene Proteins c-raf Mitogen-Activated Protein Kinase Kinases MAP Kinase Kinase 1 Phytohemagglutinins Cell Division Enzyme Activation Amino Acid Sequence Molecular Sequence Data Proto-Oncogene Proteins p21(ras) Protein-Tyrosine Kinases Lymphotoxin-alpha Calcium-Calmodulin-Dependent Protein Kinases Protein Serine-Threonine Kinases |
Appears in Collections: | Aurora harvest 5 Paediatrics publications |
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