Stimulation of phosphoinositol turnover and protein kinase C activation by granulocyte-macrophage colony-stimulating factor in HL-60 cells.
Phosphoinositol turnover, diacylglycerol generation, protein kinase C (PK-C) activity, and intracellular cyclic nucleotides were studied in an established human leukemia cell line, HL-60, in response to one of the hematopoietic cytokines, granulocyte-macrophage colony-stimulating factor (GM-CSF). Continuous exposure of HL-60 cells to GM-CSF induced the cell differentiation that was evaluated by the nitroblue tetrazolium (NBT) reducing activity. GM-CSF also exhibited a proliferative effect on HL-60 cells. GM-CSF at 1 nmol/L, an optimal concentration for cell growth and cell differentiation, induced significant changes in the intracellular inositoltriphosphate (IP3). Diacylglycerol generation was also stimulated by GM-CSF treatment. GM-CSF increased the membrane PK-C activity by 10-fold of the control, whereas no measurable change in cyclic nucleotides was observed. These data indicated that phosphoinositol turnover and the activation of PK-C were included in the GM-CSF signal transducing pathway in HL-60 cell. Phosphoinositol response leading to PK-C activation may act as a trigger signal of cell differentiation by GM-CSF.
Nishimura
M
M
Third Department of Internal Medicine, School of Medicine, University of Yamaguchi, Japan.
Kaku
K
K
Azuno
Y
Y
Okafuji
K
K
Inoue
Y
Y
Kaneko
T
T
D002454:Cell Differentiation; D002455:Cell Division; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D004075:Diglycerides / Q000378:metabolism; D004789:Enzyme Activation; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006801:Humans; D007295:Inositol Phosphates / Q000378:metabolism*; D007700:Kinetics; D015473:Leukemia, Promyelocytic, Acute; D011493:Protein Kinase C / Q000378:metabolism*; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
D004075:Diglycerides; D007295:Inositol Phosphates; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D000242:Cyclic AMP; D011493:Protein Kinase C; D006152:Cyclic GMP