ABSTRACT
The G-protein cycle exemplified for the b2AR (11) is shown in Figure 14.1. Binding of an agonist to the b2AR induces a conformational change in the receptor. The agonist-bound b2AR then interacts with the GDP-liganded Gsprotein (stimulatory G-protein of adenylyl cyclase). The Gs-protein consists of three subunits, that is, the name-giving Gsa subunit as well as a b-and g-subunit that form a tight complex under physiological conditions (4,5). The agonistbound b2AR promotes dissociation of GDP from Gsa, that is, the receptor acts as guanine nucleotide exchange factor (GEF). Subsequently, a ternary complex consisting of agonist, b2AR and nucleotide-free G-protein forms (11). This complex possesses high agonist affinity and facilitates the binding of GTP to Gsa. GTP-binding to Gsa causes a substantial conformational change in this G-protein subunit, resulting in the disruption of the ternary complex and dissociation of the Gs-protein heterotrimer into Gsa and the bg-complex. GTPbound Gsa activates the effector protein adenylyl cyclase (AC). AC catalyzes the conversion of ATP into the second messenger cAMP that subsequently activates downstream proteins such as cAMP-dependent protein kinase and cAMPregulated cation channels. Termination of Gs-protein activation is achieved by the GTPase activity of Gsa, cleaving GTP into GDP and inorganic phosphate (Pi). GDP-bound Gsa and the bg-complex reassociate, closing the G-protein cycle. All bxARs couple to Gs-proteins. Additionally, the b2AR can also couple to inhibitory G-protein of adenylyl cyclase (Gi-proteins), resulting in activation of the mitogen-activated protein kinase pathway (12-14).
