Mimicry of phorbol ester responses by diacylglycerols. Differential effects on phosphatidylcholine biosynthesis, cell-cell communication and epidermal growth factor binding.
The biosynthesis of phosphatidylcholine (PC) in HEL-37 cells was followed by measuring the incorporation of [32P]Pi into PC. Incorporation was stimulated by 12-O-tetradecanoylphorbol 13-acetate (TPA) and by the synthetic diacylglycerol, sn-1,2-dioctanoylglycerol (diC8), but not by sn-1-oleoyl-2-acetylglycerol or sn-1,2-dihexanoylglycerol (diC6). DiC8 was rapidly metabolised by HEL-37 cells to the corresponding PC and phosphatidic acid derivatives. diC8, diC6 and oleoylacetylglycerol effectively displaced [3H]phorbol-12,13-dibutyrate bound to a soluble cell extract from HEL-37 cells, but only diC8 was able to displace the labelled phorbol ester from prelabelled cells. TPA, diC8, diC6 and oleoylacetylglycerol were all effective inhibitors of 125I-labelled epidermal growth factor binding to, and gap junctional communication between, HEL-37 cells. It is concluded that only cell-permeable diacylglycerols stimulate PC biosynthesis which may therefore require interaction with membranes other than the plasma membrane.
D000818:Animals; D002450:Cell Communication / Q000187:drug effects*; D002460:Cell Line; D004075:Diglycerides / Q000494:pharmacology*; D004815:Epidermal Growth Factor / Q000378:metabolism*; D004817:Epidermis; D005989:Glycerides / Q000494:pharmacology*; D007365:Intercellular Junctions / Q000187:drug effects; D051379:Mice; D010704:Phorbols / Q000494:pharmacology*; D010713:Phosphatidylcholines / Q000096:biosynthesis*; D011493:Protein Kinase C / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D004075:Diglycerides; D005989:Glycerides; D010704:Phorbols; D010713:Phosphatidylcholines; C044295:1,2-dioctanoylglycerol; D004815:Epidermal Growth Factor; C038237:1-oleoyl-2-acetylglycerol; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate