Cyclic AMP inhibits the activity of c-Jun N-terminal kinase (JNKp46) but not JNKp55 and ERK2 in human helper T lymphocytes

The cyclic AMP (cAMP) elevating agent PGE, and dibutyryl cyclic AMP (dBcAMP ) affect T cell functions. Using human helper T cell clones, we examined ef fects of cAMP on c-Jun N-terminal kinase (JNK) and extracellular signal-reg ulated kinase (ERK), which are assumed to play a role in T cell regulation. When we analyzed the effects of dBcAMP on activities of mitogen-activated protein kinase (MAPK) family members ERK2, JNKp55 and JNKp46, dBcAMP did no t inhibit the activities of ERK2 and JNKp55 induced by PMA/A23187 stimulati on. JNKp46 activity was, however, inhibited by dBcAMP. JNK phosphorylates c -Jun on Ser-63 and Ser-73, the result being induction of its transcriptiona l activity. We found that dBcAMP inhibited the phosphorylation of c-Jun Ser -63 induced by PMA/A23187 stimulation. We suggest a different mechanism of regulation of JNKp55 and JNKp46 activities and that JNKp46 is a specific c- Jun kinase by which the activity of c-Jun is regulated in T lymphocytes. (C ) 1999 Academic Press.