INVOLVEMENT OF PROTEIN-KINASE-C IN THE ACTIVATION OF EXTRACELLULAR SIGNAL-REGULATED KINASE-1 2 BY UVC IRRADIATION/

UVC irradiation activates mitogen-activated protein kinases (MAPKs), i ncluding ERK, JNK, and P38. This study examined the role of protein ki nase C (PKC) in the regulation of UVC-stimulated MAPKs activation. Eit her the depletion of PKC by prolonged treatment of cells with 12-O-tet radecanoylphorbol-13-acetate (TPA) or the inhibition of PKC by a selec tive PKC inhibitor, UCN-01-ME, attenuated UVC-activation of ERK1/2, ke eping the activation of JNK1/2 intact. However, K252a, a non-selective PKC inhibitor, inhibited the activation of both ERK1/2 and JNK1/2 by UVC. In three isoforms of PKC (alpha, delta, epsilon) examined, PKC ep silon shows the most evident translocation, a temporal association wit h cell membrane, upon the UVC irradiation of NIH 3T3 cells. These resu lts suggest that PKC is acting in the UVC-dependent activation of ERK1 /2, and PKC epsilon is one of the PKC isozymes playing such a role. (C ) Academic Press.