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 often lead to alteration in activity and/or subcellular distribution, indicating that changes are non-tolerable at many of the amino acid positions. Particularly, Arg201 and Gln227 are critical, since modifications of these residues, such as ADP-ribosylation of Arg201 that can be induced by cholera toxin or mutations at either residue, lead to inhibition of the GTPase activity and, therefore, render Gsα constitutively active [18-21]. The receptor and GTPase dependent activation cycle of Gsα, structural features of Gsα protein, and the roles of specific Gs effectors have been reviewed in more detail elsewhere [22, 23].
