Direct evidence that ERK regulates the production/secretion of interleukin-2 in PHA/PMA-stimulated T lymphocytes

Although p21(ras), raf-l and MEK have been shown to regulate directly the t ranscriptional activity of NFAT (nuclear factor of activated T cells) and/o r the interleukin-2 (IL-2) promoter, direct evidence that the extracellular signal-regulated protein kinase (ERK) is involved in regulating IL-2 produ ction is still lacking. Here, we demonstrate that transfection of Jurkat ce lls with a dominant negative mutant of ERK1 (Erkl-K71R) resulted in the sup pression of mitogen-stimulated production/secretion of IL-2. This was accom panied by a parallel inhibition of mitogen-stimulated ERK activity. These d ata provide direct evidence, for the first time, that ERK plays a vital rol e in regulating the production/secretion of IL-2.