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The p38 Mitogen-Activated Protein Kinase Pathway in Activated and Anergic Th1 Cells

Stimulation of T cells through the TCR leads to activation of the mitogen-activated protein kinase (MAPK) family members ERK (extracellular signal-regulated kinase) and JNK (jun NH2-terminal kinase). These kinases act in synergy to increase the activity of the transcription factor AP-1 which is invo...

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Bibliographic Details
Published in:Cellular immunology 1997-09, Vol.180 (2), p.116-123
Main Authors: Desilva, Dimuthu R., Jones, Elizabeth A., Feeser, Wendi S., Manos, Elizabeth J., Scherle, Peggy A.
Format: Article
Language:English
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Summary:Stimulation of T cells through the TCR leads to activation of the mitogen-activated protein kinase (MAPK) family members ERK (extracellular signal-regulated kinase) and JNK (jun NH2-terminal kinase). These kinases act in synergy to increase the activity of the transcription factor AP-1 which is involved in the transcriptional upregulation of IL-2. Recently a third MAPK member, p38, has been identified. The effects of T cell activation on this pathway have not yet been elucidated. Using two murine Th1 clones, we demonstrate that the p38 pathway is induced upon anti-CD3 plus anti-CD28 crosslinking or PMA plus ionomycin stimulation. p38 activity was induced fully by anti-CD3 or PMA alone and is not enhanced by costimulation even at low levels of TCR signaling. p38 activity peaked at 20 min and was significantly decreased by 2 hr. Anergic (tolerant) Th1 cells showed decreased p38 activity as well as decreased ERK and JNK activities even though levels of these proteins remained unchanged.
ISSN:0008-8749
1090-2163
DOI:10.1006/cimm.1997.1182