Bombesin and zinc enhance the synergistic mitogenic effects of insulin and phosphocholine by a MAP kinase-dependent mechanism in Swiss 3T3 cells.

Simultaneous treatment of serum-starved (24 h) Swiss 3T3 cells with insulin (500 nM) and phosphocholine (PCho) (0.25-1 mM) resulted in synergistic stimulation of DNA synthesis via a mitogen activated protein (MAP) kinase-independent rapamycin-sensitive mechanism. Co-treatment of cells with bombesin (10 nM) or zinc (25 microM) enhanced the combined mitogenic effects of insulin and PCho 2-3-fold; however, in the presence of bombesin or zinc the combined effects of insulin and PCho were not inhibited by rapamycin. The potentiating effects of bombesin and zinc on insulin plus PCho-induced DNA synthesis were accompanied by large stimulation of p42 MAP kinase activity. The results indicate that in Swiss 3T3 cell cultures, synergistic stimulation of DNA synthesis by extracellular insulin and PCho via a p42 MAP kinase-dependent mechanism requires the presence of other growth regulatory agents, such as bombesin or zinc.