Gs protein

The G_s alpha subunit (G_αs, G_sα) is a subunit of the heterotrimeric G protein G_s that stimulates the cAMP-dependent pathway by activating adenylyl cyclase. G_sα is a GTPase that functions as a cellular signaling protein.
G_sα is the founding member of one of the four families of heterotrimeric G proteins, defined by the alpha subunits they contain: the G_αs family, G_αi/G_αo family, G_αq family, and G_α12/G_α13 family. The Gs-family has only two members: the other member is G_olf, named for its predominant expression in the olfactory system. In humans, G_sα is encoded by the GNAS complex locus, while G_olfα is encoded by the GNAL gene.

Function

The general function of G_s 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 G_sα, 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 G_sα 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_sα acting through PKA are described here.

Although each GTP-bound G_sα can activate only one adenylyl cyclase enzyme, amplification of the signal occurs because one receptor can activate multiple copies of G_s while that receptor remains bound to its activating agonist, and each G_sα-bound adenylyl cyclase enzyme can generate substantial cAMP to activate many copies of PKA.

Receptors

The G protein-coupled receptors that couple to the G_s family proteins include:
* 5-HT receptors types 5-HT₄ and 5-HT₇
* ACTH receptor a.k.a. MC2R
* Adenosine receptor types A_2a and A_2b
* Arginine vasopressin receptor 2
* β-adrenergic receptors types β₁, β₂ and β₃
* Calcitonin receptor
* Calcitonin gene-related peptide receptor
*Cannabinoid receptor 2
* Corticotropin-releasing hormone receptor
* Dopamine receptors D₁-like family ( D₁ and D₅), mainly through G_olf in the striatum
* FSH-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 G_olf in the olfactory neurons
* Parathyroid hormone receptor 1
* Prostaglandin receptor types D₂ and I₂
* Secretin receptor
* Thyrotropin receptor
* Trace amine-associated receptor 1

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

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Peripheral membrane proteins
Medical mnemonics