Nature 301, 621 - 623 (17 February 1983); doi:10.1038/301621a0

Phorbol esters increase the amount of Ca²⁺, phospholipid-dependent protein kinase associated with plasma membrane

Andrew S. Kraft & Wayne B. Anderson^*

Laboratory of Pathophysiology, National Cancer Institute, Building 10, Room B1B47, Bethesda, Maryland 20205, USA
^*Present address: Laboratory of Tumor Immunology and Biology, National Cancer Institute, Building 10, Room 8B02, Bethesda, Maryland 20205, USA.

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^1,2 and phospholipid metabolism³⁻⁷. A protein kinase activity has recently been described which is dependent on calcium and acidic phospholipids and is further enhanced by diacylglycerol⁸⁻¹⁰. 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 cells¹¹. 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.

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