Activation of mitogen-activated protein kinase by the carcinogenic mycotoxin fumonisin B1.
Recent studies indicate that the mycotoxin and putative carcinogen fumonisin B1 stimulates mitogenesis in Swiss 3T3 fibroblasts. Because mitogen-activated protein kinase (MAPK) is a key enzyme in the signal transduction pathways activated by many mitogens, we hypothesized that fumonisin B1 might modulate MAPK activity. Consistent with other reports, we observed that fumonisin B1 is synergistic with insulin for mitogenesis in Swiss 3T3 cells. We also observed that: (1) fumonisin B1 stimulates rapid, transient activation of MAPK; and (2) the dose-response curve for fumonisin B1-stimulated activation of MAPK is similar to the dose-response curve for the mitogenic effects of fumonisin B1. In contrast to fumonisin B1, insulin stimulates minimal activation of MAPK in Swiss 3T3 cells. The observation that fumonisin B1 and insulin differ with respect to the modulation of MAPK activity suggests a possible mechanism for their synergistic stimulation of mitogenesis in Swiss 3T3 cells.
Wattenberg
E V
EV
Division of Environmental and Occupational Health, University of Minnesota, Minneapolis 55455, USA. evwatt@mail.eoh.umn.edu
Badria
F A
FA
Shier
W T
WT
D016475:3T3 Cells; D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D002274:Carcinogens, Environmental / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D004789:Enzyme Activation; D037341:Fumonisins; D007328:Insulin / Q000494:pharmacology; D007700:Kinetics; D051379:Mice; D009183:Mycotoxins / Q000494:pharmacology*
D002274:Carcinogens, Environmental; D037341:Fumonisins; D007328:Insulin; D009183:Mycotoxins; C056933:fumonisin B1; D017871:Calcium-Calmodulin-Dependent Protein Kinases