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Direct evidence that ERK regulates the production/secretion of interleukin-2 in PHA/PMA-stimulated T lymphocytes
1Department of Immunopathology, Womens' and Children's Hospital, North Adelaide, Australia.
Abstract:
Although p21ras, raf-1 and MEK have been shown to regulate directly the transcriptional activity of NFAT (nuclear factor of activated T cells) and/or the interleukin-2 (IL-2) promoter, direct evidence that the extracellular signal-regulated protein kinase (ERK) is involved in regulating IL-2 production is still lacking. Here, we demonstrate that transfection of Jurkat cells with a dominant negative mutant of ERK1 (Erk1-K71R) resulted in the suppression of mitogen-stimulated production/secretion of IL-2. This was accompanied by a parallel inhibition of mitogen-stimulated ERK activity. These data provide direct evidence, for the first time, that ERK plays a vital role in regulating the production/secretion of IL-2.
Insights
Extracellular signal-regulated kinase (ERK) is crucial for interleukin-2 (IL-2) production. This study shows that inhibiting ERK activity suppresses IL-2 secretion, providing direct evidence for ERK
Area of Science:
- Immunology
- Molecular Biology
- Cell Signaling
Background:
- The p21ras, raf-1, and MEK pathways are known regulators of the nuclear factor of activated T cells (NFAT) and the interleukin-2 (IL-2) promoter.
- Direct evidence linking extracellular signal-regulated kinase (ERK) to the regulation of IL-2 production has been previously lacking.
Purpose of the Study:
- To investigate the direct role of ERK in regulating IL-2 production and secretion.
- To provide definitive evidence for ERK's involvement in the mitogen-stimulated IL-2 pathway.
Main Methods:
- Transfection of Jurkat cells with a dominant-negative mutant of ERK1 (Erk1-K71R).
- Stimulation of cells with mitogens to induce IL-2 production and ERK activity.
- Measurement of IL-2 production/secretion and ERK activity.
Main Results:
- Transfection with dominant-negative ERK1 significantly suppressed mitogen-stimulated IL-2 production and secretion.
- Inhibition of ERK activity was observed in parallel with the suppression of IL-2 secretion.
Conclusions:
- Extracellular signal-regulated kinase (ERK) plays a vital role in regulating IL-2 production and secretion.
- These findings provide the first direct evidence for ERK's critical involvement in the IL-2 production pathway.