OKADAIC ACID INCREASED ANNEXIN-I AND INDUCED-DIFFERENTIATION OF HUMANPROMYELOCYTIC LEUKEMIA-CELLS

The differentiation of a cell line of human promyelocytic leukemia, HL -60 cells, triggered by 12-O-tetradecanoyl 13-phorbol acetate (TPA), d epends on the phosphorylation of some proteins, such as 17, 27, and 34 kDa proteins, by protein kinase C. For elucidation of the mechanism o f ligand-induced differentiation of HL-60 cells, the effects of okadai c acid (OA), a phosphatase inhibitor, on cell differentiation and prot ein phosphorylation were studied. After treatment with OA, HL-60 cells differentiated into macrophage-like cells; within 16 h, 70% or more o f the treated cells adhered to plastic dishes. The adherent cells did not undergo mitosis but began activities such as phagocytosis. OA incr eased the phosphorylation of 17, 23, 27, and 34 kDa proteins, as did T PA. The amount of annexin I (39 kDa protein) in HL-60 cells caused to differentiate with OA was 7.5-fold that without such treatment. Kineti c analysis showed that increased transcription of annexin I mRNA cause d the increase in annexin I in the differentiated cells. Thus, OA and TPA increased cellular levels of annexin I and caused the differentiat ion of HL-60 cells into macrophage-like cells.