AJP - Cell Physiology, Vol 257, Issue 6 C1113-C1118, Copyright © 1989 by American Physiological Society
External Mg2+-dependent early stimulation of nucleotide synthesis in Swiss 3T3 cells
S. Ishijima, K. Kita and M. Tatibana
Department of Biochemistry, Chiba University School of Medicine, Inohana, Japan.
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.
