Control of ion fluxes by mitogenic polypeptides

Several ion fluxes are stimulated when mitogenic polypeptides are added to cells. The precise mechanism by which this activation takes place is not understood, but compelling evidence exists in the case of the activation of sodium-hydrogen exchange that it requires the tyrosine kinase activity associated with the mitogen receptor. The activation of sodium-hydrogen exchange by mitogens is associated with changes in intracellular pH that appear to be permissive but not causal in allowing cells to proceed through the cell cycle. When added to cells, mitogens also activate protein kinase C, which acts as part of a feedback loop to control the activity of the mitogen receptor. Possible mechanisms for this control are discussed.