Involvement of a pertussis-toxin sensitive G protein in the induction of gene expression by insulin

Binding of insulin to its receptor triggers multiple cellular responses, including changes in metabolism and in gene expression, resulting from the activation of multiple signalling pathways. Pertussis toxin has been shown to block an insulin-stimulated phospholipase C, resulting in an inhibition of the synthesis of phospholipid second messengers by insulin. In the present study, we investigated the significance of this pathway for the induction of growth-related genes by insulin treatment of H35 hepatoma cells. We found that pertussis toxin dramatically inhibits the induction of c-fos mRNA by insulin. Although c-jun and ornithine decarboxylase induction were also inhibited by pertussis toxin, they were much less sensitive than c-fos. These results indicate an important role for lipid second messengers in mitogenic signalling by insulin and further demonstrate distinct roles for this pathway in the induction of c-fos and c-jun.