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 In the field of molecular biology, the cAMP-dependent pathway, also known as the adenylyl cyclase pathway, is a G protein-coupled receptor-triggered signaling cascade used in cell communication. Discovery cAMP was discovered by Earl Sutherla ...

by activating

adenylyl cyclase Adenylate cyclase (EC 4.6.1.1, also commonly known as adenyl cyclase and adenylyl cyclase, abbreviated AC) is an enzyme with systematic name ATP diphosphate-lyase (cyclizing; 3′,5′-cyclic-AMP-forming). It catalyzes the following reaction: :A ...

. G_sα is a

GTPase GTPases are a large family of hydrolase enzymes that bind to the nucleotide guanosine triphosphate (GTP) and hydrolyze it to guanosine diphosphate (GDP). The GTP binding and hydrolysis takes place in the highly conserved P-loop "G domain", a ...

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 Guanine nucleotide-binding protein G(olf) subunit alpha is a protein that in humans is encoded by the ''GNAL'' gene. Its main product is the heterotrimeric G-protein alpha subunit Golf-α, a member of the Gs alpha subunit family that is a key co ...

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 A hormone (from the Ancient Greek, Greek participle , "setting in motion") is a class of cell signaling, signaling molecules in multicellular organisms that are sent to distant organs or tissues by complex biological processes to regulate physio ...

neurotransmitter A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a Chemical synapse, synapse. The cell receiving the signal, or target cell, may be another neuron, but could also be a gland or muscle cell. Neurotra ...

), the activated receptor acts as a

guanine nucleotide exchange factor Guanine nucleotide exchange factors (GEFs) are proteins or protein domains that activate monomeric GTPases by stimulating the release of guanosine diphosphate (GDP) to allow binding of guanosine triphosphate (GTP). A variety of unrelated structu ...

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

to produce the

second messenger Second messengers are intracellular signaling molecules released by the cell in response to exposure to extracellular signaling molecules—the first messengers. (Intercellular signals, a non-local form of cell signaling, encompassing both first m ...

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 An agonist is a chemical that activates a Receptor (biochemistry), receptor to produce a biological response. Receptors are Cell (biology), cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an R ...

, 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-HT₄, 5-HT₆ and 5-HT₇ serotonergic receptors *

Adenosine receptor The adenosine receptors (or P1 receptors) are a class of Purinergic receptor, purinergic G protein-coupled receptors with adenosine as the endogenous ligand (biochemistry), ligand. There are four known types of adenosine receptors in humans: Aden ...

types A_2a and A_2b * 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 Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic chemical of the catecholamine and phenethylamine families. It is an amine synthesized ...

D₁ and D₅ receptors *

Follicle-stimulating hormone receptor The follicle-stimulating hormone receptor or FSH receptor (FSHR) is a transmembrane receptor that interacts with the follicle-stimulating hormone (FSH) and represents a G protein-coupled receptor (GPCR). Its activation is necessary for the horm ...

* Gastric inhibitory polypeptide receptor * Glucagon receptor * Growth-hormone-releasing hormone receptor * Histamine H₂ receptor * Luteinizing hormone/choriogonadotropin receptor *

Melanocortin receptor Melanocortin receptors are members of the rhodopsin family of 7-transmembrane G protein-coupled receptors. There are five known members of the melanocortin receptor system each with differing specificities for melanocortins: * . MC1R is associa ...

: MC1R, MC2R (a.k.a. ACTH receptor), MC3R, MC4R, MC5R *

Olfactory receptors Olfactory receptors (ORs), also known as odorant receptors, are chemoreceptors expressed in the cell membranes of olfactory receptor neurons and are responsible for the detection of odorants (for example, compounds that have an odor) which give ...

, through G_olf 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 Trace amine-associated receptor 1 (TAAR1) is a trace amine-associated receptor (TAAR) protein that in humans is encoded by the ''TAAR1'' gene. TAAR1 is a primarily intracellular amine-activated and G protein-coupled receptor (GPCR) that is p ...

* Vasopressin receptor 2

References

External links

* * * {{Portal bar, Biology, border=no * Peripheral membrane proteins Medical mnemonics

Function

Receptors

See also

References

External links