Phorbol esters activate the pathway for phosphatidylethanol synthesis in differentiating HL-60 cells.

12-O-Tetradecanoylphorbol 13-acetate (TPA) has been shown to induce the formation of an unusual acidic phospholipid, phosphatidylethanol, in HL-60 cells. The synthesis of this lipid is dependent upon the presence of ethanol in the culture medium of TPA-treated cells; however, other exogenous alcohols can substitute as headgroup precursors with the formation of the corresponding phosphatidyl alcohol. The activation of the pathway for phosphatidyl alcohol synthesis appears to be mediated through protein kinase C. Studies of the time-course for the synthesis and accumulation of phosphatidylethanol suggest a possible involvement of the pathway for phosphatidyl alcohol synthesis in the TPA-induced differentiation of HL-60 cells.