Phorbol esters increase the amount of Ca2+, phospholipid-dependent protein kinase associated with plasma membrane.
Although the biochemical mechanism of action of phorbol ester tumour promoters is not fully understood, it is known that phorbol ester binding to the cell surface causes rapid changes in calcium flux and phospholipid metabolism. A protein kinase activity has recently been described which is dependent on calcium and acidic phospholipids and is further enhanced by diacylglycerol. Previously, we have observed that phorbol ester treatment of EL4 mouse thymoma cells causes a rapid decrease in cytosolic calcium, phospholipid-dependent protein kinase (Ca, PL-PK) activity, which is mediated through the specific phorbol ester cell-surface receptors identified on EL4 cells. We now show that treatment of parietal yolk sacs (PYS-2) cells with biologically active 12-O-tetradecanoyl phorbol-13-acetate (TPA) provokes a rapid decrease in cytosolic Ca, PL-PK activity that is accompanied by a significant increase in the amount of Ca, PL-PK activity associated with the plasma membrane fraction. These results suggest that the rapid and tight association of Ca, PL-PK activity with the plasma membrane may be an early event in mediating some of the effects of phorbol esters.
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002462:Cell Membrane / Q000187:drug effects / Q000201:enzymology*; D005260:Female; D010703:Phorbol Esters / Q000494:pharmacology*; D010704:Phorbols / Q000494:pharmacology*; D010743:Phospholipids / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors; D015017:Yolk Sac / Q000187:drug effects / Q000201:enzymology
D010703:Phorbol Esters; D010704:Phorbols; D010743:Phospholipids; D011494:Protein Kinases; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium