The G<sub>s</sub> alpha subunit (G<sub>ñs</sub>, G<sub>s</sub>ñ) is a subunit of the heterotrimeric G protein G<sub>s</sub> that stimulates the cAMP-dependent pathway by activating adenylyl cyclase. G<sub>s</sub>ñ is a GTPase that functions as a cellular signaling protein. G<sub>s</sub>ñ is the founding member of one of the four families of heterotrimeric G proteins, defined by the alpha subunits they contain: the G<sub>ñs</sub> family, G<sub>ñi</sub>/G<sub>ño</sub> family, G<sub>ñq</sub> family, and G<sub>ñ12</sub>/G<sub>ñ13</sub> family. The Gs-family has only two members: the other member is G<sub>olf</sub>, named for its predominant expression in the olfactory system. In humans, G<sub>s</sub>ñ is encoded by the GNAS complex locus, while G<sub>olf</sub>ñ is encoded by the GNAL gene.
The general function of G<sub>s</sub> is to activate intracellular signaling pathways in response to activation of cell surface G protein-coupled receptors (GPCRs). GPCRs function as part of a three-component system of receptor-transducer-effector. The transducer in this system is a heterotrimeric G protein, composed of three subunits: a Gñ protein such as G<sub>s</sub>ñ, and a complex of two tightly linked proteins called Gò and Gó in a Gòó complex. When not stimulated by a receptor, Gñ is bound to GDP and to Gòó to form the inactive G protein trimer. When the receptor binds an activating ligand outside the cell (such as a hormone or neurotransmitter), the activated receptor acts as a guanine nucleotide exchange factor to promote GDP release from and GTP binding to Gñ, which drives dissociation of GTP-bound Gñ from Gòó. In particular, GTP-bound, activated G<sub>s</sub>ñ binds to adenylyl cyclase to produce the second messenger cAMP, which in turn activates the cAMP-dependent protein kinase (also called Protein Kinase A or PKA). Cellular effects of G<sub>s</sub>ñ acting through PKA are described here.
Although each GTP-bound G<sub>s</sub>ñ can activate only one adenylyl cyclase enzyme, amplification of the signal occurs because one receptor can activate multiple copies of G<sub>s</sub> while that receptor remains bound to its activating agonist, and each G<sub>s</sub>ñ-bound adenylyl cyclase enzyme can generate substantial cAMP to activate many copies of PKA.
The G protein-coupled receptors that couple to the G<sub>s</sub> family proteins include: