Alkyllysophospholipid ET‐18‐OCH3 acts as an activator of protein kinase C in HL‐60 cells

HL‐60 cells are very sensitive to the cytotoxic action of ether lipids. Several hypotheses have been proposed to explain this cytotoxicity. We investigated the influence of the alkylphospholipid ET‐18‐OCH3 on the activity of protein kinase C. HL‐60 cells were incubated with ET‐18‐OCH3 at a concentration of 20 μg/ml for 4 h. After the incubation the membrane fraction of the HL‐60 cells was isolated and the activity of protein kinase C was determined while it was still associated with the membrane, using the synthetic peptide substrate [Ser25]‐protein kinase C (19–31) as a protein kinase C specific substrate. The activity of the membrane‐bound protein kinase C was increased in HL‐60 cells treated with ET‐18‐OCH3 compared to untreated HL‐60 cells. The increase in protein kinase C activity was not a consequence of translocation and appeared to be additive to the effect of the phorbol ester 12‐myristate 13‐acetate. In contrast, solubilized protein kinase C from HL‐60 cells could be inhibited or stimulated in vitro by ET‐18‐OCH3, dependent on the mode of addition of ET‐18‐OCH3 and phospholipids.