Influence of tumor-promoting phorbol esters on the phosphorylation of membrane proteins in lymphocytes.
Treatment of bovine lymphocytes with 12-O-tetradecanoyl-phorbol-13-acetate (TPA) (10(-8) M) for as little as 5 min significantly alters the ability of membrane-particulate fractions to phosphorylate proteins using in situ protein kinases and exogenous [gamma-32P]ATP. After 20 min of treatment, the phosphorylation of two proteins with mol. wts. of 65K and 74K in the isolated membrane-particulate fraction is increased approximately 30-35%, whereas the phosphorylation of a 130K protein is almost completely suppressed. The ability of different phorbol esters to alter membrane protein phosphorylation correlates well with their potency as tumor promoters in mouse epidermis and as comitogens in phytohemagglutinin-treated lymphocytes. This phorbol ester response appears to have a low temperature coefficient since cells treated with TPA at 4 degrees C also responded, although at a slower rate. This action of TPA is neither mimicked nor antagonized by dibutyryl cAMP (1 mM); moreover, it is not affected by retinoic acid, an agent which blocks several other phorbol ester effects in these cells. Inhibition of protein synthesis with cycloheximide also fails to influence this response. In contrast, trifluoperazine, an inhibitor of calmodulin function and certain lipid-dependent protein kinases, depressed the phosphorylation of the 65K and 74K proteins to below the control level.
D000818:Animals; D002417:Cattle; D004305:Dose-Response Relationship, Drug; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D008565:Membrane Proteins / Q000097:blood*; D008970:Molecular Weight; D010703:Phorbol Esters / Q000494:pharmacology*; D010704:Phorbols / Q000494:pharmacology*; D010766:Phosphorylation; D013329:Structure-Activity Relationship; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors
D008565:Membrane Proteins; D010703:Phorbol Esters; D010704:Phorbols; D013755:Tetradecanoylphorbol Acetate