c-myc gene expression is stimulated by agents that activate protein kinase C and does not account for the mitogenic effect of PDGF.
The role of the phosphoinositide turnover-protein kinase C pathway in mediating PDGF-stimulated c-myc expression and cell proliferation was studied. Both direct activators of kinase C (e.g. phorbol ester analogues) and hormones that activate kinase C via receptor-mediated phosphoinositide turnover (e.g. PDGF, bradykinin, or vasopressin) elicited a rapid increase in c-myc mRNA expression. Desensitization of the kinase C pathway by prolonged exposure to phorbol abolished the induction of c-myc by subsequent phorbol challenge and attenuated c-myc induction by PDGF and bradykinin, but did not affect PDGF-stimulated mitogenesis. Bradykinin and phorbol esters stimulated the same magnitude of c-myc expression as PDGF but elicited less than one-tenth the PDGF-induced mitogenic response. We conclude that stimulation of c-myc expression is a common response to a diverse group of agents that elicit phosphoinositide turnover and activate protein kinase C, and that neither activation of protein kinase C nor enhanced c-myc expression is sufficient for the mitogenic action of PDGF.
D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004247:DNA / Q000096:biosynthesis; D004075:Diglycerides / Q000494:pharmacology; D004789:Enzyme Activation; D004815:Epidermal Growth Factor / Q000494:pharmacology; D006801:Humans; D008934:Mitogens / Q000494:pharmacology*; D010716:Phosphatidylinositols / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism*; D011519:Proto-Oncogenes; D012333:RNA, Messenger / Q000235:genetics; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013936:Thymidine / Q000378:metabolism; D014667:Vasopressins / Q000494:pharmacology
D004075:Diglycerides; D008934:Mitogens; D010716:Phosphatidylinositols; D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; D014667:Vasopressins; D004815:Epidermal Growth Factor; C038237:1-oleoyl-2-acetylglycerol; D004247:DNA; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D001920:Bradykinin; D013936:Thymidine