GNAS/Gαs (E4G1G) Rabbit mAb #47342

G protein-coupled receptors (GPCRs) transmit extracellular signals through heterotrimeric G proteins (guanine nucleotide-binding proteins) (1). G proteins have three main subunits: Gα, Gβ, and Gγ. In the quiescent state, the GDP bound Gα is associated with Gβγ. Binding of ligands to GPCR causes the exchange of GDP for GTP on Gα, leading to its dissociation from the Gβγ complex (2). The released GTP-Gα further activates downstream effectors to initiate signaling events. G-protein-mediated signaling is terminated by hydrolysis of GTP by Gα intrinsic GTP hydrolase and reassociation of Gα with Gβγ to form the inactive heterotrimer.

There are four subclasses of Gα protein, Gαs, Gαi/o, Gαq/11, and Gα12/13 (3), and each is linked to a unique signaling pathway. Gαs is encoded by the GNAS gene. This G protein subunit is associated with a wide spectrum of disorders (4). The GTP bound Gαs activates adenylyl cyclase, which catalyzes the conversion of ATP into the second messenger cAMP and initiates the downstream PKA pathway (5). Mutations on residue Arg201 or Gln227 result in loss of GTP hydrolase activity (6), leading to constitutive activation of Gαs, which contributes to tumor progression (7,8), fibrous dysplasia of bone (9), and McCune-Albright syndrome, a disorder that causes abnormal skin pigmentation, scar tissue formation on bone, and growth-regulating gland malfunction (10). Heterozygous loss-of-function mutations in Gαs lead to Albright hereditary osteodystrophy (AHO), a disease characterized by short stature, obesity, brachydactyly, subcutaneous ossification, and dental deficits (11).