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Stimulation of phosphoinositol turnover and protein kinase C activation by granulocyte-macrophage colony-stimulating factor in HL-60 cells

M Nishimura, K Kaku, Y Azuno, K Okafuji, Y Inoue and T Kaneko

Third Department of Internal Medicine, School of Medicine, University of Yamaguchi, Japan.

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.

Volume 80, Issue 4, pp. 1045-1051, 08/15/1992
Copyright © 1992 by The American Society of Hematology


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