Tumor-promoting, phorbol ester-induced phosphorylation of cell-surface transferrin receptors in human erythroleukemia cells

When human erythroleukemia cells (K562) were exposed to phorbol-12-myristate 13-acetate (PMA), phosphorylation of transferrin receptors was enhanced 5-fold with 10(-7) M PMA and 7-fold with 10(-6) M PMA, but not with 4 alpha-phorbol (5 X 10(-7) M). Stimulation took place in serine residues in the cytoplasmic domain of the receptor. Although phosphorylation in the control cells took place in both cell-surface and intracellular receptors, phosphorylation in PMA-treated cells increased only in the cell-surface receptors, not in the intracellular receptors. The number of receptors on the cell surface increased slightly with the increase in phosphorylation at the cell surface, in the PMA-treated cells. No difference in transferrin binding was found for the control and PMA-treated cells. These results indicate that enhanced phosphorylation of the transferrin receptor takes place on the cell surface only and that it presumably is mediated by protein kinase C.