Induction of c-jun independent of PKC, pertussis toxin-sensitive G protein, and polyamines in quiescent SV40-transformed 3T3 T cells.
CSV3 clones of simian virus 40 large T antigen-transformed murine 3T3 T cells can be made quiescent as part of a differentiation process. In these quiescent cells, insulin- and vanadate-induced mitogenesis are both associated with the induction of the c-jun proto-oncogene (Wang and Scott 1991 J. Cell. Physiol. 147, 102-110; Wang et al. 1991 Cell Growth Differ. 2, 645-652). The current studies were therefore designed to compare the early signal transduction pathways employed by insulin and vanadate to regulate c-jun expression. In quiescent CSV3-1 cells, down-regulation of protein kinase C by prolonged exposure to 12-O-tetra-decanoylphorbol-13-acetate or inhibition of protein kinase C activity by treatment with the protein kinase C antagonist staurosporine is shown not to affect c-jun induction by insulin or vanadate. This suggests that both insulin and vanadate act in a protein kinase C-independent manner. Insulin's effect on c-jun induction does, however, involve a G protein because insulin's effect can be inhibited by pertussis toxin. In contrast, vanadate induction of c-jun is not affected by pertussis toxin. Genistein, a general tyrosine kinase inhibitor, can inhibit the ability of vanadate to induce c-jun but it does not inhibit insulin's effect. Finally, the depletion of polyamines, particularly spermidine, by DL-alpha-difluoromethylornithine treatment also prevents c-jun induction by insulin but DL-alpha-difluoromethylornithine treatment has no effect on c-jun induction by vanadate. These observations indicate that the c-jun induction by insulin and vanadate in CSV3-1 cells is mediated by different signal transduction mechanisms. Together with our previously published data, these results suggest that c-jun can be induced independent of protein kinase C activation, without involvement of pertussis toxin-sensitive G protein, independent of induction of c-fos, and without expression of high levels of intracellular polyamines.
Wang
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Department of Pathology, University of Tennessee Medical Center, Memphis 38163.
Scott
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D016475:3T3 Cells; D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000235:genetics*; D002455:Cell Division / Q000187:drug effects; D002461:Cell Line, Transformed; D000518:Eflornithine / Q000494:pharmacology*; D019204:GTP-Binding Proteins / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects; D016758:Genes, jun; D019833:Genistein; D007328:Insulin / Q000494:pharmacology; D007529:Isoflavones / Q000494:pharmacology; D007700:Kinetics; D051379:Mice; D037342:Pertussis Toxin; D011073:Polyamines / Q000378:metabolism* / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000096:biosynthesis* / Q000235:genetics; D011700:Putrescine / Q000494:pharmacology; D015398:Signal Transduction; D013539:Simian virus 40 / Q000235:genetics*; D013095:Spermidine / Q000494:pharmacology; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014638:Vanadates / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
D000470:Alkaloids; D000952:Antigens, Polyomavirus Transforming; D007328:Insulin; D007529:Isoflavones; D011073:Polyamines; D016755:Proto-Oncogene Proteins c-jun; D010566:Virulence Factors, Bordetella; D014638:Vanadates; D019833:Genistein; D037342:Pertussis Toxin; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C; D019204:GTP-Binding Proteins; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate; D013095:Spermidine; D011700:Putrescine; D000518:Eflornithine