C-JUN N-TERMINAL PHOSPHORYLATION CORRELATES WITH ACTIVATION OF THE JNK SUBGROUP BUT NOT THE ERK SUBGROUP OF MITOGEN-ACTIVATED PROTEIN-KINASES

c-Jun transcriptional activity is stimulated by phosphorylation at two N-terminal sites: Ser-63 and -73. Phosphorylation of these sites is e nhanced in response to a variety of extracellular stimuli, including g rowth factors, cytokines, and W irradiation. New members of the mitoge n-activated protein (MAP) kinase group of signal-transducing enzymes, termed JNKs, bind to the activation domain of c-Jun and specifically p hosphorylate these sites. However, the N-terminal sites of c-Jun were also suggested to be phosphorylated by two other MAP kinases, ERK1 and ERK2. Despite these reports, we find that unlike the JNKs, ERK1 and E RK2 do not phosphorylate the N-terminal sites of c-Jun in vitro; inste ad they phosphorylate an inhibitory C-terminal site. Furthermore, the phosphorylation of c-Jun in vivo at the N-terminal sites correlates wi th activation of the JNKs but not the ERKs. The ERKs are probably invo lved in the induction of c-fos expression and thereby contribute to th e stimulation of AP-1 activity. Our study suggests that two different branches of the MAP kinase group are involved in the stimulation of AP -1 activity through two different mechanisms.