Augmentation of retinoic acid-induced granulocytic differentiation in HL-60 leukemia cells by serine/threonine protein phosphatase inhibitors

• Published in: FEBS letters Vol. 314; no. 3; pp. 340 - 344
• Main Authors: Morita, Koichi, Nishikawa, Masakatsu, Kobayashi, Kazuhiko, Deguchi, Katsumi, Itoh, Masaaki, Nakano, Takeshi, Shima, Hiroshi, Nagao, Minako, Kuno, Takayoshi, Tanaka, Chikako, Shirakawa, Shigeru
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 21.12.1992
• Subjects: Calycutin-A; Cell Adhesion; Cell Differentiation - drug effects; Cell Differentiation - physiology; Chromatography, Agarose; Differentiation; Ethers, Cyclic - pharmacology; Granulocytes - cytology; HL-60 cell; Humans; Leukemia; Macrophages - cytology; Okadaic Acid; Oxazoles - pharmacology; Phosphatase; Phosphoprotein Phosphatases - antagonists & inhibitors; Phosphoprotein Phosphatases - physiology; Phosphorylation; Tetradecanoylphorbol Acetate - pharmacology; Tretinoin - pharmacology; Tumor Cells, Cultured; Okadaic Acid; Differentiation; Phosphatase; HL-60 cell; Calycutin-A
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/0014-5793(92)81501-C

To evaluate the involvement of protein phosphatases (PP) in differentiation of human myclogenous leukemia HL-60 cells, we made use of potent inhibitors of PP1 and PP2A, calyculin-A (CAL-A) and okadaic acid (OKA). CAL-A and OKA could augment all- trans retinoic acid (ATRA)-induced granulocytic differentiation, whereas the differentiation toward macrophage lineage by 12- o-tetradecanoylphorbol acetate (TPA) was unchanged in the presence of CAL-A. CAL-A augmented the phosphorylation or 18K, 23K and 30K proteins induced by ATRA. The PP1 and PP2A were identified and were present mainly in the cytosol of HL-60 cells. These results suggest that either PP1 or PP2A or both may be involved in regulating granulocytic differentiation or HL-60 cells.