Protein kinase C levels and protein phosphorylation associated with inhibition of proliferation in a murine macrophage tumor.
Treatment of M5076 tumor cells with the phorbol estes 12-O-tetradecanoylphorbol 13-acetate (TPA) and phorbol 12,13 dibutyrate (PdBu) inhibited cellular proliferation, whereas 1,2-dioctanoyl-glycerol (DiC8) and 1-oleoyl2-acetyl-glycerol (OAG) did not affect cell growth. Inhibition of cellular proliferation in this cell line appears to be a consequence of protein kinase C (PKC) down-regulation since phorbol esters, but not a single application of diacylglycerols (DGs) down-regulated cellular PKC levels. By repeated application of DGs, PKC down-regulation was achieved and correlated with inhibition of proliferation. Phorbol ester-induced PKC down-regulation was reversible, upon removal of the phorbol ester, and the reappearance of PKC was associated with resumption of proliferation. The mitogenic responsiveness of these cells to added serum depended upon cellular PKC levels. Phorbol esters also caused the phosphorylation of two proteins which were not phosphorylated in response to DG treatment. Inhibition of growth of M5076 cells appears to be associated with phosphorylation of two novel proteins and/or PKC down-regulation.
Goode
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NT
Imperial Cancer Research Fund, London, England.
Hart
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IR
D000818:Animals; D002455:Cell Division; D004075:Diglycerides / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D007526:Isoelectric Point; D008264:Macrophages / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D008970:Molecular Weight; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D010750:Phosphoproteins / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism*; D012513:Sarcoma, Experimental; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors; D014407:Tumor Cells, Cultured
D004075:Diglycerides; D010750:Phosphoproteins; D015240:Phorbol 12,13-Dibutyrate; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate