Gsα is a ubiquitous protein whose activity is essential for the cellular actions of many neurotransmitters, autocrine/paracrine factors, and hormones. As in α-subunits of other heterotrimeric G proteins, activation of Gsα by an agonist-occupied cell surface receptor results in a GDP-GTP exchange on Gsα, causing dissociation of the latter from Gβγ subunits and, thereby, allowing both Gsα and Gβγ to stimulate their respective effectors. GTP-bound, free Gsα can directly activate several different effectors, including Src tyrosine kinase [15] and certain Ca-channels [16, 17]. However,by far the most ubiquitous and the most extensively investigated effector molecule stimulated by Gsα is adenylyl cyclase, an integral membrane protein that catalyzes the synthesis of the ubiquitous second messenger cyclic AMP (cAMP), thereby triggering an intracellular signaling cascade that brings about an agonist- and cell-specific response. The activation of adenylyl cyclase and other effectors by Gsα is tightly regulated. The intrinsic GTP hydrolase (GTPase) activity of Gsα reverts the GTP-bound Gsα to its GDP-bound state and, thereby, results in the re-assembly of the G protein heterotrimer, which can no longer mediate effector stimulation. Mutagenesis experiments
