Synergistic signals in mitogenesis: role of ion fluxes, cyclic nucleotides and protein kinase C in Swiss 3T3 cells.

A fundamental feature in the action of most mitogenic agents when added to quiescent cells in serum-free medium is that they exhibit striking synergistic effects when applied in specific combinations. A tenable hypothesis of growth control must provide a cogent explanation for the molecular mechanisms underlying this complex pattern of synergistic effects. To gain an understanding of the mechanisms by which these synergistic effects arise, we studied the initial cellular responses associated with the interaction of mitogenic factors and hormones with the cell, including changes in cation fluxes, cyclic nucleotides and cellular phosphoproteins. In this paper, some of our recent results on the early signals and responses elicited by multiple growth-promoting agents in quiescent cultures of Swiss 3T3 cells will be summarized. On the basis of the emerging information, we propose a framework that integrates early events and synergistic effects in a unified hypothesis of growth control.