External Mg2+-dependent early stimulation of nucleotide synthesis in Swiss 3T3 cells

In quiescent Swiss 3T3 cells, metabolic flux through phosphoribosyl pyrophosphate into nucleotides increased within 1 h when various growth factors were added (S. Ishijima, K. Kita, N. Kinoshita, T. Ishizuka, N. Suzuki, and M. Tatibana. J. Biochem. 104: 570-575, 1988). The divalent cation ionophore A23187 mimicked the stimulatory effect of epidermal growth factor plus insulin, thereby suggesting involvement of divalent cation mobilization in signaling the stimulation by the growth factors. The stimulation induced by the growth factors was nil in medium devoid of added Mg2+ but was not affected by the omission of Ca2+. The dependency on external Mg2+ was also observed with the stimulations by bombesin plus insulin, fibroblast growth factor, and A23187. In contrast, the mitogenic stimulation of glycolysis was observed irrespective of the presence or absence of Mg2+, indicating that initial events in the signaling process, including mitogen binding to receptors, took place in the absence of exogenous Mg2+. These results suggest that a Mg2(+)-dependent process, subsequent to growth factor binding to receptors, plays an essential role in signaling the early mitogenic stimulation of nucleotide synthesis.