How is the hormone-activated synthesis of the second messenger cyclic AMP regulated? Or, in more general terms, how does the interaction of an extracellular agonist with a receptor lead to intracellular enzyme activity when receptor and enzyme are not distinct macromolecules? The mediators are membrane-bound, guanine nucleotide binding regulatory proteins (G proteins). When the receptor is activated, G proteins dissociate into their subunits. These in turn activate or inhibit enzymes such as adenylate cyclases, which catalyze the synthesis of cyclic AMP. In these signal transmission processes G proteins act as molecular switches and amplifiers.