Role of protein kinase C in adriamycin-induced erythroid differentiation of K562 cells.

Modulators of protein kinase C (PKC) were used to investigate the role of this enzyme during Adriamycin-induced erythroid differentiation of K562 cells. Adriamycin (0.1 microM) induced erythroid differentiation in 60% +/- 10% of K562 cells. Phorbol myristate-12-acetate, an activator of protein kinase C, was strongly anti-proliferative to K562 cells (IC50, 8 nM) but did not induce erythroid differentiation. Staurosporine inhibited PKC from K562 cells (IC50, 8 nM) and blocked Adriamycin-induced erythroid differentiation, but only at concentrations marginally below those that inhibited proliferation (IC50, 81 nM), 1-(5-Isoquinolinylsulphonyl)-2-methylpiperazine (H-7) inhibited K562 PKC (IC50, 26 microM) but reduced Adriamycin-induced differentiation by less than 50% at concentrations of up to 600 microM. These data argue against a major role for PKC during Adriamycin-induced erythroid differentiation in K562 cells.