Fig. 1. G protein activation/deactivation cycle. This figure depicts activation of the stimulatory G protein (Gs) by the ßAR receptor, but a similar activation/deactivation cycle is thought to occur with most (if not all) G proteins. The G protein 
subunit cycles between an inactive GDP-bound heterotrimeric (ß
) form and an active GTP-bound monomeric form. At rest, an equilibrium exists between the receptor in the high-affinity state (coupled to the G protein) and the low-affinity (uncoupled) state. Activation of receptors by an agonist induces a conformational change in the receptor, allowing it to interact with the G protein, leading to the release of GDP, and the formation of a high-affinity ternary complex (agonist-receptor-G protein). This high-affinity state is short lived, and binding of GTP to the empty nucleotide site on the subunit of the G protein leads to a destabilization of the high-affinity complex and a dissociation of the G protein into s-GTP and ß subunits. It is now well established that both the s-GTP and ß subunits are able to regulate the activity of various effectors. To date, the best characterized effects of the G protein ß subunits are potentiation of the activity of ACs II and IV and activation of certain PLC isozymes, ion channels, and receptor kinases. s-GTP is shown to activate ACs in this figure, but there is also evidence demonstrating the direct activation of L-type Ca2+ channels by s-GTP (at least in certain tissues). The continued activation of effectors by -GTP is terminated by the action of a GTPase enzyme intrinsic to the a subunit. The formation of s-GDP causes its dissociation from AC; the reassociation of s-GDP with ß is thermodynamically stable and completes the cycle with the formation of the inactive GDP-bound heterotrimeric (ß) G protein. ATP = adenosine triphosphate; PLC ß = phospholipase C ß isoenzyme; s = subunit of stimulatory G protein; ß = G protein ß subunits.
