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 in sulin (500 nM) and phosphocholine (PCho) (0.25-1 mM) resulted in syner gistic stimulation elf DNA synthesis via a mitogen activated protein ( MAP) kinase-independent rapamycin-sensitive mechanism. Co-treatment of cells with bombesin (10 nM) or zinc (25 mu M) enhanced the combined m itogenic effects of insulin and PCho 2-3-fold; however, in the presenc e of bombesin or zinc the combined effects of insulin and PCho were no t inhibited by rapamycin. The potentiating effects of bombesin and zin c 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 e xtracellular insulin and PCho via a p42 MAP kinase-dependent mechanism requires the presence of other growth regulatory agents, such as bomb esin or zinc. (C) 1997 Federation of European Biochemical Societies.