Leukaemia inhibitory factor induces mitogenesis in Swiss 3T3 cells and selective enhancement via a variety of signalling events.
Leukaemia inhibitory factor (LIF) stimulates cellular DNA synthesis in confluent quiescent Swiss 3T3 cells. Insulin and prostaglandin E1 (PGE1), which fail to stimulate DNA synthesis alone, potentiate this effect. Prostaglandin F2alpha (PGF2alpha), which is mitogenic in these cells, enhances the effect of LIF on DNA synthesis. TGFbeta1 increases the effect of PGF2alpha but not that of LIF. R-59022, a diacylglycerol kinase inhibitor which increases protein kinase C (PKC) activity, enhances only the PGF2alpha response. 13-Tetradecanoyl-12-phorbolacetate-mediated PKC depletion prevents the action of PGF2alpha but not that of LIF, nor the PGF2alpha potentiation of LIF-stimulated DNA synthesis. 1-Oleoyl-2acetylglycerol, a PKC and tyrosine kinase (TK) activator which mimics some of the PGF2alpha effects, enhances only LIF-induced DNA synthesis in cells possessing intact PKC activity. These results suggest that stimulation of DNA synthesis by LIF, as well as its enhancement by PGF2alpha, may occur via a signalling pathway independent of PKC activation.
Levy
C S
CS
Instituto de Investigaciones Bioquimicas Fundacion Campomar, Buenos Aires, Argentina.
Sauane
M
M
Rudland
P S
PS
Jimenez de Asua
L
L
D016475:3T3 Cells; D000527:Alprostadil / Q000494:pharmacology; D000818:Animals; D004247:DNA / Q000096:biosynthesis; D019852:Diacylglycerol Kinase; D015237:Dinoprost / Q000494:pharmacology; D004357:Drug Synergism; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006131:Growth Inhibitors / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines / Q000494:pharmacology*; D051379:Mice; D008938:Mitosis; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000037:antagonists & inhibitors; D011493:Protein Kinase C / Q000378:metabolism; D011744:Pyrimidinones / Q000494:pharmacology; D015398:Signal Transduction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000494:pharmacology
D004791:Enzyme Inhibitors; D006131:Growth Inhibitors; D007328:Insulin; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; C507838:Lif protein, mouse; D008222:Lymphokines; D011744:Pyrimidinones; D013844:Thiazoles; D016212:Transforming Growth Factor beta; D004247:DNA; C047505:R 59022; D015237:Dinoprost; D017853:Phosphotransferases (Alcohol Group Acceptor); D019852:Diacylglycerol Kinase; D011493:Protein Kinase C; D000527:Alprostadil; D013755:Tetradecanoylphorbol Acetate