Augmentation of retinoic acid-induced granulocytic differentiation in HL-60 leukemia cells by serine/threonine protein phosphatase inhibitors.
To evaluate the involvement of protein phosphatases (PP) in differentiation of human myelogenous 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 of 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 of HL-60 cells.
Morita
K
K
First Department of Internal Medicine, Mie University School of Medicine, Japan.
Nishikawa
M
M
Kobayashi
K
K
Deguchi
K
K
Ito
M
M
Nakano
T
T
Shima
H
H
Nagao
M
M
Kuno
T
T
Tanaka
C
C
D002448:Cell Adhesion; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002847:Chromatography, Agarose; D004988:Ethers, Cyclic / Q000494:pharmacology; D006098:Granulocytes / Q000166:cytology*; D006801:Humans; D007938:Leukemia; D008264:Macrophages / Q000166:cytology; D008387:Marine Toxins; D019319:Okadaic Acid; D010080:Oxazoles / Q000494:pharmacology; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors / Q000502:physiology*; D010766:Phosphorylation; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014212:Tretinoin / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D004988:Ethers, Cyclic; D008387:Marine Toxins; D010080:Oxazoles; D019319:Okadaic Acid; D014212:Tretinoin; C059041:calyculin A; D010749:Phosphoprotein Phosphatases; D013755:Tetradecanoylphorbol Acetate