Adenylate cyclase and cyclic AMP phosphodiesterase of normal and Rous sarcoma virus transformed chicken embryo fibroblasts.

Abstract

AbstractCyclic AMP appears to regulate cell growth. Cyclic AMP levels are high in normal chicken embryo fibroblasts and drop to very low levels when the cells are transformed by the Bryan high‐titer strain of Rous sarcoma virus. Cells infected with a temperature‐sensitive mutant of the virus have normal levels of cyclic AMP at the nonpermissive (nontransforming temperature), but when the cells are shifted to the permissive (transforming) temperature the cyclic AMP levels rapidly fall to values that are found in transformed cells. Studies on the adenylate cyclase and cyclic AMP phosphodiesterase in normal and transformed chicken embryo fibroblasts have shown that the adenylate cyclase is greatly decreased in the transformed cells whereas the phosphodiesterase is increased. The decrease in adenylate cylcase activity is the result of an increase in the Km of the substrate and a loss of a magnesium ion activator site. The increase in phosphodiesterase activity is the result of an increase in total phosphodiesterase activity and a decrease in the negative cooperativity of plasma membrane bound phosphodiesterase. Thus the fall in cyclic AMP levels that occurs on transformation can be correlated with changes in the activity of adenylate cyclase and cyclic AMP phosphodiesterase.