C-JUN N-TERMINAL KINASE BUT NOT MITOGEN-ACTIVATED PROTEIN-KINASE IS SENSITIVE TO CAMP INHIBITION IN T-LYMPHOCYTES

The molecular mechanism underlying the cAMP inhibition of nuclear acti vation events in T lymphocytes is unknown. Recently, the activation of fibroblasts and muscle cells are shown to be antagonized by cAMP thro ugh the inhibition of mitogen-activated protein (MAP) kinases signalin g pathway. Whether a similar antagonism may account for the late inhib itory effect of cAMP in T cell was examined. Surprisingly, extracellul ar signal regulated kinase 2 (ERK2) activation was resistant to cAMP i nhibition in all the T lymphocytes tested. Different isoforms (ERK1, E RK2, and ERK3) of MAP kinase were poorly inhibited by cAMP. High conce ntration of cAMP also only weakly antagonized Raf-1 in T cells. The re sistance of ERK and Raf-1 to cAMP clearly distinguishes T cells from f ibroblasts. In contrast, another MAP kinase homologue c-Jun N-terminal kinase (JNK) was inhibited by cAMP in good correlation with that of I L-2 suppression. Moreover, JNK was antagonized by a delayed kinetics w hich is characteristic of cAMP inhibition. Despite that both ERK and J NK are essential for T cell activation, selective inhibition by cAMP f urther supports the specific role of JNK in T cell activation.