“…We had also established that there are marked differences between the regulation of G-proteins by the coupled receptors and the regulation of adenylyl cyclase by G-proteins (42,43). When the structures and regulatory properties of adenylyl cyclases became known (61), particularly the fact that these are transmembrane proteins that have a twocassette structure (i.e., two distinct domains on a 12 membrane-spanning structure,) it became possible to construct a more coherent theory to explain the regulation of the cyclase system (62). Two regulatory cycles, one for regulation of multimer to monomer G-proteins, the other for regulation of cyclase by a monomeric G-protein (GS) are illustrated in Figure 2.…”