Plasma membrane-associated increase in guanylate cyclase activity in regenerating rat liver

Abstract

CYCLIC GMP has been postulated as one of the intracellular mediators triggering cell growth¹. Exogenously added cylic GMP or its derivatives are liable to induce a substantial increase in DNA synthesis^2–4 and to promote growth^2,5. Cultured, non-transformed fibroblasts⁶ and lymphocytes¹ exist in one of two reversible growth states, a state of rapid proliferation and a state of relative quiescence and increased levels of cylic GMP are correlated with the transition from the resting to the growth state^1,3. In these systems, a variety of mitogenic agents have been shown to initiate proliferation of quiescent cells and this effect seems to be accomplished by interaction with the cell surface¹. Therefore, if an increase in cylic GMP levels were to act as the intracellular signal triggering cell proliferation, its formation and/or degradation should be linked to events occurring in the plasma membrane. Indeed, a membrane-bound guany-late cyclase (GTP pyrophosphatelyase, cyclising, EC 4.6.1.2.) of cultured fibroblasts has been found to be activated by a fibroblast growth factor⁷.