Okadaic acid increased annexin I and induced differentiation of human promyelocytic leukemia cells.
The differentiation of a cell line of human promyelocytic leukemia, HL-60 cells, triggered by 12-O-tetradecanoyl 13-phorbol acetate (TPA), depends on the phosphorylation of some proteins, such as 17, 27, and 34 kDa proteins, by protein kinase C. For elucidation of the mechanism of ligand-induced differentiation of HL-60 cells, the effects of okadaic acid (OA), a phosphatase inhibitor, on cell differentiation and protein phosphorylation were studied. After treatment with OA, HL-60 cells differentiated into macrophage-like cells; within 16 h, 70% or more of the treated cells adhered to plastic dishes. The adherent cells did not undergo mitosis but began activities such as phagocytosis. OA increased the phosphorylation of 17, 23, 27, and 34 kDa proteins, as did TPA. 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. Kinetic analysis showed that increased transcription of annexin I mRNA caused the increase in annexin I in the differentiated cells. Thus, OA and TPA increased cellular levels of annexin I and caused the differentiation of HL-60 cells into macrophage-like cells.
Sato
E F
EF
Department of Biochemistry, Osaka City University Medical School, Japan.
Edashige
K
K
Inoue
M
M
Utsumi
K
K
D017305:Annexin A1 / Q000235:genetics / Q000378:metabolism*; D002448:Cell Adhesion; D002454:Cell Differentiation / Q000187:drug effects*; D002455:Cell Division; D002460:Cell Line / Q000187:drug effects; D004988:Ethers, Cyclic / Q000494:pharmacology*; D006801:Humans; D007951:Leukemia, Myeloid; D019319:Okadaic Acid; D010766:Phosphorylation; D012333:RNA, Messenger / Q000032:analysis; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D017305:Annexin A1; D004988:Ethers, Cyclic; D012333:RNA, Messenger; D019319:Okadaic Acid; D013755:Tetradecanoylphorbol Acetate