Application of phorbol ester to mouse skin causes a rapid and sustained loss of protein kinase C.
It is now widely accepted that tumour-promoting phorbol esters activate a Ca2+- and phospholipid-dependent protein kinase (protein kinase C) both in vitro and in intact cells, and that the kinase represents a major cellular phorbol ester-binding protein. The phorbol esters act as analogues of diacylglycerol, a natural regulator of protein kinase C, and stabilize the membrane-association of the kinase. Although other molecular targets may exist, protein kinase C activation is probably important in mediating the diverse responses of cultured cells to phorbol esters and in promoting in vivo tumours. The enzyme comprises a family of closely related proteins and has been detected in extracts from mouse epidermal cells, the likely targets for two-stage carcinogenesis in mouse skin. In this report we show that application of a single dose of TPA (12-O-tetradecanoyl phorbol-13-acetate) to mouse skin results in a rapid and complete loss of protein kinase C activity which is maintained for 3-4 days. This is associated with a loss of immunologically detectable protein kinase C and the accumulation of a smaller protein detectable by antibodies recognizing the regulatory domain of protein kinase C.
Fournier
A
A
School of Biological Sciences, Flinders University of South Australia, Bedford Park.
Murray
A W
AW
D000818:Animals; D007158:Immunologic Techniques; D051379:Mice; D008970:Molecular Weight; D010446:Peptide Fragments / Q000378:metabolism; D011493:Protein Kinase C / Q000276:immunology / Q000378:metabolism*; D012867:Skin / Q000187:drug effects* / Q000201:enzymology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D013997:Time Factors
D010446:Peptide Fragments; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate