Colony-stimulating factor 1 activates protein kinase C in human monocytes.
Colony-stimulating factor 1 (CSF-1) is required for the survival, proliferation and differentiation of monocytes. We previously demonstrated that the CSF-1 receptor is linked to a pertussis toxin-sensitive G protein and that the induction of Na+ influx by CSF-1 is a pertussis toxin-sensitive event. The present studies have examined activation of protein kinase C as a potential intracellular signaling event induced by the activated CSF-1 receptor. The results demonstrate that CSF-1 stimulates translocation of protein kinase C activity from the cytosol to membrane fractions. This activation of protein kinase C was sensitive to pretreatment of the monocytes with pertussis toxin. Lipid distribution studies demonstrated that phosphatidylcholine (PC) is the major phospholipid in human monocytes. Moreover, the results indicate that CSF-1 stimulation is associated with decreases in PC, but not in phosphatidylinositol (PI), levels. The absence of an effect of CSF-1 on PI turnover was confirmed by the lack of changes in inositol phosphate production. In contrast, CSF-1 stimulation was associated with increased hydrolysis of PC to phosphorylcholine and diacylglycerol (DAG) in both intact monocytes and cell-free assays. Furthermore, the increase in PC turnover induced by CSF-1 was sensitive to pertussis toxin. The results also demonstrate that the induction of Na+ influx by CSF-1 is inhibited by the protein kinase C inhibitors staurosporine and the isoquinoline derivative H7, but not by HA1004.(ABSTRACT TRUNCATED AT 250 WORDS)
Laboratory of Clinical Pharmacology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115.
K
K
Imamura
A
A
Dianoux
T
T
Nakamura
D
D
Kufe
D002478:Cells, Cultured; D003115:Colony-Stimulating Factors / Q000494:pharmacology*; D004075:Diglycerides / Q000096:biosynthesis / Q000097:blood; D004789:Enzyme Activation; D006801:Humans; D006868:Hydrolysis; D007700:Kinetics; D016173:Macrophage Colony-Stimulating Factor; D008563:Membrane Lipids / Q000097:blood; D009000:Monocytes / Q000201:enzymology*; D019301:Oleic Acid; D009829:Oleic Acids / Q000097:blood; D037342:Pertussis Toxin; D010713:Phosphatidylcholines / Q000097:blood; D010740:Phospholipases / Q000097:blood; D010743:Phospholipids / Q000097:blood; D011493:Protein Kinase C / Q000097:blood*; D012964:Sodium / Q000097:blood; D013229:Stearic Acids / Q000097:blood; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D003115:Colony-Stimulating Factors; D004075:Diglycerides; D008563:Membrane Lipids; D009829:Oleic Acids; D010713:Phosphatidylcholines; D010743:Phospholipids; D013229:Stearic Acids; D010566:Virulence Factors, Bordetella; D019301:Oleic Acid; C031183:stearic acid; D016173:Macrophage Colony-Stimulating Factor; D012964:Sodium; D037342:Pertussis Toxin; D011493:Protein Kinase C; D010740:Phospholipases