IL-3-induced generation of alkylacylglycerol and diacylglycerol in an IL-3-dependent cell line.
The hematopoietic growth factor IL-3 promotes the proliferation and development of several hematopoietic lineages. Inasmuch as protein kinase C has been suggested to mediate the response of IL-3, we examined the accumulation of diradylglycerols (DG) in response to IL-3 in CFTL-12 cells, a murine mast cell line that requires IL-3 for growth. Exposure of CFTL-12 cells to IL-3 resulted in the conversion of [3H]myristate-labeled lipids to DG. Mass analysis of the DG of CFTL-12 cells cultured in the presence of IL-3 showed that 58% was the ether-linked form, alkylacylglycerol, and 42% was diacylglycerol. The levels of both alkylacylglycerol and diacylglycerol declined when CFTL-12 cells were withdrawn from IL-3 and became quiescent. Stimulation of quiescent cells with IL-3 produced an acute increase in the mass of both alkylacylglycerol and diacylglycerol, consistent with phosphatidylcholine as a significant source. The effects of PMA on the generation of DG were examined to explore the role of protein kinase C activation in the response to IL-3. PMA stimulated an increase in DG accumulation that was not augmented by the simultaneous addition of IL-3. Down-modulation of protein kinase C by long term PMA treatment reduced, but did not eliminate, the IL-3-stimulated increase in DG, suggesting that protein kinase C activation results in an amplification of the initial accumulation of DG. These results indicate a role for DG, generated through the hydrolysis of phosphatidylcholine, in the induction of protein kinase C activity and the events leading to cell proliferation in response to IL-3.
Department of Biochemistry, James H. Quillen College of Medicine, East Tennessee State University, Johnson City 37614.
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Robinson
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Chen
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Warne
D000215:Acylation; D000818:Animals; D002460:Cell Line; D004075:Diglycerides / Q000096:biosynthesis*; D007073:Immunoglobulin E / Q000276:immunology; D007377:Interleukin-3 / Q000494:pharmacology*; D051379:Mice; D010713:Phosphatidylcholines / Q000378:metabolism; D011493:Protein Kinase C / Q000502:physiology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D004075:Diglycerides; D007377:Interleukin-3; D010713:Phosphatidylcholines; D007073:Immunoglobulin E; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate