Differential effects of various protein kinase C activators on protein phosphorylation in human acute myeloblastic leukemia cell line KG-1 and its phorbol ester-resistant subline KG-1a.
Human myeloid leukemia KG-1 cells are induced to differentiate to macrophage-like cells by tumor-promoting phorbol esters, such as 12-O-tetradecanoylphorbol-13-acetate (TPA). Cells from the cloned subline, KG-1a, unlike the parental line, are resistant to the differentiating effect of TPA. In the present studies, we investigated in these cells protein phosphorylation stimulated by various protein kinase C activators, including 1-oleoyl-2-acetylglycerol in the presence of the diacylglycerol kinase inhibitor R59022, TPA, mezerein, and bryostatin. All the agents stimulated, to a greater extent and with a higher potency, phosphorylation of several proteins in KG-1 cells than in KG-1a cells. On the other hand, these agents markedly stimulated phosphorylation of other proteins in KG-1a cells compared to that in KG-1 cells. The findings indicated that the actions of the diacylglycerol, 1-oleoyl-2-acetylglycerol, and the non-metabolizable activators (TPA, mezerein, and bryostatin) were very similar but not fully equivalent; and that KG-1a cells exhibited altered (increased or decreased) phosphorylation patterns, perhaps related to the TPA resistance characteristic of this subline of cells.
Kiss
Z
Z
Deli
E
E
Shoji
M
M
Koeffler
H P
HP
Pettit
G R
GR
Vogler
W R
WR
Kuo
J F
JF
D054713:Bryostatins; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D004075:Diglycerides / Q000494:pharmacology; D004224:Diterpenes; D004351:Drug Resistance; D004789:Enzyme Activation; D006801:Humans; D007783:Lactones / Q000494:pharmacology; D015470:Leukemia, Myeloid, Acute / Q000378:metabolism* / Q000473:pathology; D018942:Macrolides; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D011744:Pyrimidinones / Q000494:pharmacology; D013729:Terpenes / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D013844:Thiazoles / Q000494:pharmacology
D054713:Bryostatins; D004075:Diglycerides; D004224:Diterpenes; D007783:Lactones; D018942:Macrolides; D011506:Proteins; D011744:Pyrimidinones; D013729:Terpenes; D013844:Thiazoles; C011309:mezerein; C046785:bryostatin 1; C038237:1-oleoyl-2-acetylglycerol; C047505:R 59022; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate