Adenylate cyclase activity of normal and transformed fibroblasts in culture

The intracellular concentration of cyclic AMP regulates many cellular properties of normal rat, mouse, and human fibroblasts in culture. Thus it is important to elucidate how the activity of adenylate cyclase of fibroblasts might be altered and regulated by both intracellular and extracellular agents and events. In studies with several virally transformed fibroblast lines, as well as those transformed spontaneously or by 3-methylcholanthrene, a common feature of each type of transformation is a defective adenylate cyclase system. However, the means by which adenylate cyclase activity is altered differs with the cell system and the type of transformation. Here we concentrate on efforts to understand the regulatory properties of the adenylate cyclase from normal rat kidney fibroblasts. The modulation (increase or decrease) of the hormonal responsiveness of this enzyme may play an important role in its regulation. Of substantial interest is the isolation from serum of a high-molecular weight factor that selectively decreases the GTP and hormone-stimulated activities of adenylate cyclase. These findings are of value in our attempts at elucidation of the reasons for altered cyclase activity following virus transformation and during various stages of growth.