ULTRAVIOLET B-INDUCED ACTIVATED PROTEIN-1 ACTIVATION DOES NOT REQUIREEPIDERMAL GROWTH-FACTOR RECEPTOR BUT IS BLOCKED BY A DOMINANT-NEGATIVE PKC-LAMBDA I/

The exposure of mammalian cells to UV irradiation leads to the activat ion of transcription factors such as activated protein-1 (AP-1) and NF kappa B. It is postulated that epidermal growth factor (EGF) receptor , but not protein kinase C (PKC), is the major membrane mediator in UV -induced signal transduction. Since UVB is responsible for most of the carcinogenic effects of sun exposure, we investigated the role of EGF receptors and PKC in UVB-induced AP-1 activation. Our results indicat ed that while the down-regulation of novel PKC (nPKC) and conventional PKC (cPKC) by pretreatment of cells with 12-O-tetradecanoyl phorbol-1 3-actetate cannot block UVB-induced AP-1 activity, it can block 12-O-t etradecanoyl phorbol-13-acetate-induced AP-I activity, Further, the do minant negative mutant PKC lambda/iota blocked UVB-induced AP-1 activi ty in all doses and time courses studied. In contrast, UVB-induced AP- 1 activity from cells devoid of EGF receptor (B82) was not significant ly different from that of the stable transfectants with a kinase-defic ient EGF receptor (B82M721) or those with a wild-type EGF receptor (B8 2L) at all UVB irradiation doses and time courses studied, All of this evidence indicated that aPKC, but not EGF receptor, is involved in UV E-induced AP-1 activation.