Signalling mitogenesis in 3T3 cells: role of monovalent ion fluxes and cyclic nucleotides

Quiescent 3T3 cells resting in the G0 phase of the cell cycle can be stimulated to reinitiate DNA synthesis by combinations of chemically diverse agents which act synergistically when added to cultures maintained in serum-free medium. Understanding of the mechanism(s) whereby extracellular agents interact in modulating cell proliferation requires the identification of the intracellular signals important for initiating a mitogenic response. Our recent evidence indicates that increases in ion fluxes involving Na+, H+, K+, and Ca2+ and elevations in cyclic AMP (cAMP) levels (produced by cholera toxin, adenosine agonists, prostaglandin E1, or cAMP derivatives) can act as mitogenic signals for Swiss 3T3 cells. We propose that initiation of DNA synthesis can be elicited by the synergistic interaction of two identifiable signals, namely, an enhanced rate of ion movements and an increase in the cellular level of cAMP.