G_q alpha subunit

G_q protein alpha subunit is a family of heterotrimeric G protein alpha subunits. This family is also commonly called the G_q/11 (G_q/G₁₁) family or G_q/11/14/15 family to include closely related family members. G alpha subunits may be referred to as G_q alpha, G_αq, or G_qα. G_q proteins couple to

• G_αq is encoded by the gene GNAQ.
• G_α11 is encoded by the gene GNA11.
• G_α14 is encoded by the gene GNA14.
• G_α15 is encoded by the gene GNA15.

Function

The general function of G_q 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.^[1][2] The transducer in this system is a heterotrimeric G protein, composed of three subunits: a Gα protein such as G_αq, and a complex of two tightly linked proteins called Gβ and Gγ in a Gβγ complex.^[1][2] When not stimulated by a receptor, Gα is bound to guanosine diphosphate (GDP) and to Gβγ to form the inactive G protein trimer.^[1][2] 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 guanosine triphosphate (GTP) binding to Gα, which drives dissociation of GTP-bound Gα from Gβγ.^[1][2] Recent evidence suggests that Gβγ and Gαq-GTP could maintain partial interaction via the N-α-helix region of Gαq.^[3] GTP-bound Gα and Gβγ are then freed to activate their respective downstream signaling enzymes.

G_q/11/14/15 proteins all activate beta-type

DAG works together with released calcium to activate specific isoforms of PKC, which are activated to phosphorylate other molecules, leading to further altered cellular activity.[4]

Further reading:

function of protein kinase C

The Gαq / Gα11 (Q209L) mutation is associated with the development of uveal melanoma and its pharmacological inhibition (cyclic depsipeptide FR900359 inhibitor), decreases tumor growth in preclinical trials.^[5][6]

Receptors

The following

• 5-HT₂ serotonergic receptors
• Alpha-1 adrenergic receptor
• Vasopressin type 1 receptors:
  1B
• Angiotensin II receptor type 1
• Calcitonin receptor
• Histamine H1 receptor
• Metabotropic glutamate receptor, Group I
• muscarinic receptors^[7]
• Trace amine-associated receptor 1

At least some Gq-coupled receptors (e.g., the muscarinic acetylcholine M₃ receptor) can be found preassembled (pre-coupled) with G_q. The common polybasic domain in the C-tail of G_q-coupled receptors appears necessary for this receptor¬G protein preassembly.[7]

Inhibitors

• The cyclic depsipeptides FR900359 and YM-254890 are strong, highly specific inhibitors of Gq and G11.^[8][9]

See also

• Second messenger system
• G protein-coupled receptor
• Heterotrimeric G protein
• Phospholipase C
• Calcium signaling
• Protein kinase C
• Gs alpha subunit
• Gi alpha subunit
• G12/G13 alpha subunits

References