Induction of protein kinase C activity by ultraviolet radiation.
Exposure to ultraviolet (UV) radiation has been well correlated with skin cancer incidence. Long wave UV radiation (320-400 nm, UVA) is a major component of natural sunlight and cosmetic tanning 'salon' light, and has been shown not only to damage DNA and to act as a complete carcinogen, but also to promote ultraviolet B (280-320 nm, UVB) carcinogenesis. The mechanism by which the latter occurs is unknown, but it is believed to be related to the inflammation and irritation which results from UV exposure. In order to examine the possibility that UVA stimulates the same signalling pathway as do the phorbol esters, a class of much more thoroughly characterized skin tumor promoters, we exposed cells in culture to UVA radiation and measured cellular responses related to protein kinase C (PKC) activation. The data presented here demonstrate that a low, physiologic dose of UVA inhibits epidermal growth factor binding and increases PKC activity in cultured mammalian fibroblasts. The increase in cytosolic activity is not completely translocated to the membrane, and can be partially suppressed by puromycin and cycloheximide but not by actinomycin D. These observations are the first evidence to suggest that a protein which has been strongly linked to chemical tumor promotion may also be a critical mediator for UV-induced promotion. The response of cells to UVA is also unique, in that it does not cause a 12-O-tetradecanoyl phorbol-13-acetate-like rapid redistribution of PKC activity followed by down regulation.
Matsui
M S
MS
Department of Dermatology, Columbia University, New York, NY 10032.
DeLeo
V A
VA
D000818:Animals; D002478:Cells, Cultured; D003609:Dactinomycin / Q000494:pharmacology; D004790:Enzyme Induction / Q000528:radiation effects; D004815:Epidermal Growth Factor / Q000378:metabolism; D015151:Immunoblotting; D051379:Mice; D015240:Phorbol 12,13-Dibutyrate / Q000378:metabolism; D010770:Phosphotransferases / Q000032:analysis; D011493:Protein Kinase C / Q000096:biosynthesis*; D012867:Skin / Q000528:radiation effects; D014466:Ultraviolet Rays / Q000009:adverse effects*
D003609:Dactinomycin; D015240:Phorbol 12,13-Dibutyrate; D004815:Epidermal Growth Factor; D010770:Phosphotransferases; D011493:Protein Kinase C