• Source: Gs alpha subunit

The Gs alpha subunit (Gαs, Gsα) is a subunit of the heterotrimeric G protein Gs that stimulates the cAMP-dependent pathway by activating adenylyl cyclase. Gsα is a GTPase that functions as a cellular signaling protein.
Gsα is the founding member of one of the four families of heterotrimeric G proteins, defined by the alpha subunits they contain: the Gαs family, Gαi/Gαo family, Gαq family, and Gα12/Gα13 family. The Gs-family has only two members: the other member is Golf, named for its predominant expression in the olfactory system. In humans, Gsα is encoded by the GNAS complex locus, while Golfα is encoded by the GNAL gene.




Function



The general function of Gs 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 Gα protein such as Gsα, and a complex of two tightly linked proteins called Gβ and Gγ in a Gβγ complex. When not stimulated by a receptor, Gα is bound to GDP and to Gβγ 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 Gα, which drives dissociation of GTP-bound Gα from Gβγ. In particular, GTP-bound, activated Gsα 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 Gsα acting through PKA are described here.
Although each GTP-bound Gsα can activate only one adenylyl cyclase enzyme, amplification of the signal occurs because one receptor can activate multiple copies of Gs while that receptor remains bound to its activating agonist, and each Gsα-bound adenylyl cyclase enzyme can generate substantial cAMP to activate many copies of PKA.




Receptors


The G protein-coupled receptors that couple to the Gs family proteins include:

5-HT4, 5-HT6 and 5-HT7 serotonergic receptors
Adenosine receptor types A2a and A2b
Adrenocorticotropic hormone receptor (a.k.a. MC2R)
Arginine vasopressin receptor 2
β-adrenergic receptors types β1, β2 and β3
Calcitonin receptor
Calcitonin gene-related peptide receptor
Corticotropin-releasing hormone receptor
Dopamine D1 and D5 receptors
Follicle-stimulating hormone receptor
Gastric inhibitory polypeptide receptor
Glucagon receptor
Growth-hormone-releasing hormone receptor
Histamine H2 receptor
Luteinizing hormone/choriogonadotropin receptor
Melanocortin receptor: MC1R, MC2R (a.k.a. ACTH receptor), MC3R, MC4R, MC5R
Olfactory receptors, through Golf in the olfactory neurons
Parathyroid hormone receptors PTH1R and PTH2R
Prostaglandin receptor types D2 and I2
Secretin receptor
Thyrotropin receptor
Trace amine-associated receptor 1
Vasopressin receptor 2




See also


Second messenger system
G protein-coupled receptor
Heterotrimeric G protein
Adenylyl cyclase
Protein kinase A
Gi alpha subunit
Gq alpha subunit
G12/G13 alpha subunits




References






External links


G(s)alpha at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
GNAS+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
Overview of all the structural information available in the PDB for UniProt: P63092 (Guanine nucleotide-binding protein G(s) subunit alpha isoforms short) at the PDBe-KB.

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