Gq Alpha Subunit
Get Gq Alpha Subunit essential facts below. View Videos or join the Gq Alpha Subunit discussion. Add Gq Alpha Subunit to your PopFlock.com topic list for future reference or share this resource on social media.
Gq Alpha Subunit
guanine nucleotide binding protein (G protein), alpha 14
Identifiers
SymbolGNA14
NCBI gene9630
HGNC4382
OMIM604397
RefSeqNM_004297
UniProtO95837
Other data
LocusChr. 9 q21
guanine nucleotide binding protein (G protein), alpha 15 (Gq class)
Identifiers
SymbolGNA15
NCBI gene2769
HGNC4383
OMIM139314
RefSeqNM_002068
UniProtP30679
Other data
LocusChr. 19 p13.3

Gq protein alpha subunit is a family of heterotrimeric G protein alpha subunits. This family is also commonly called the Gq/11 (Gq/G11) family or Gq/11/14/15 family to include closely related family members. G alpha subunits may be referred to as Gq alpha, G?q, or Gq?. Gq proteins couple to G protein-coupled receptors to activate beta-type phospholipase C (PLC-?) enzymes. PLC-? in turn hydrolyzes phosphatidylinositol 4,5-bisphosphate (PIP2) to diacyl glycerol (DAG) and inositol trisphosphate (IP3). IP3 acts as a second messenger to release stored calcium into the cytoplasm, while DAG acts as a second messenger that activates protein kinase C (PKC).

Family members

In humans, there are four distinct proteins in the Gq alpha subunit family:

  • Gq? is encoded by the gene GNAQ.
  • G11? is encoded by the gene GNA11.
  • G14? is encoded by the gene GNA14.
  • G15? is encoded by the gene GNA15.

Function

The general function of Gq 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 G? protein such as Gq?, and a complex of two tightly linked proteins called G? and G? in a G complex.[1][2] When not stimulated by a receptor, G? is bound to guanosine diphosphate (GDP) and to G 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 G?, which drives dissociation of GTP-bound G? from G.[1][2] Recent evidence suggests that G and G?q-GTP could maintain partial interaction via the N-?-helix region of G?q.[3] GTP-bound G? and G are then freed to activate their respective downstream signaling enzymes.

Gq/11/14/15 proteins all activate beta-type phospholipase C (PLC-?) to signal through calcium and PKC signaling pathways.[4] PLC-? then cleaves a specific plasma membrane phospholipid, phosphatidylinositol 4,5-bisphosphate (PIP2) into diacyl glycerol (DAG) and inositol 1,4,5-trisphosphate (IP3). DAG remains bound to the membrane, and IP3 is released as a soluble molecule into the cytoplasm. IP3 diffuses to bind to IP3 receptors, a specialized calcium channel in the endoplasmic reticulum (ER). These channels are specific to calcium and only allow the passage of calcium from the ER into the cytoplasm. Since cells actively sequester calcium in the ER to keep cytoplasmic levels low, this release causes the cytosolic concentration of calcium to increase, causing a cascade of intracellular changes and activity through calcium binding proteins and calcium-sensitive processes.[4]

Further reading: Calcium function in vertebrates

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 G?q / G?11 (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]

Receptors

The following G protein-coupled receptors couple to Gq subunits:

At least some Gq-coupled receptors (e.g., the muscarinic acetylcholine M3 receptor) can be found preassembled (pre-coupled) with Gq. The common polybasic domain in the C-tail of Gq-coupled receptors appears necessary for this receptor¬G protein preassembly.[6]

See also

References

  1. ^ a b c d Gilman AG (1987). "G proteins: transducers of receptor-generated signals". Annual Review of Biochemistry. 56: 615-649. doi:10.1146/annurev.bi.56.070187.003151. PMID 3113327.
  2. ^ a b c d Rodbell M (1995). "Nobel Lecture: Signal transduction: Evolution of an idea". Bioscience Reports. 15 (3): 117-133. doi:10.1007/bf01207453. PMID 7579038. S2CID 11025853.
  3. ^ Cervantes-Villagrana RD, Adame-García SR, García-Jiménez I, Color-Aparicio VM, Beltrán-Navarro YM, König GM, Kostenis E, Reyes-Cruz G, Gutkind JS, Vázquez-Prado J (January 2019). "G Signaling to the Chemotactic Effector P-REX1 and Mammalian Cell Migration Is Directly Regulated by G?qand G?13 Proteins". J Biol Chem. 294 (2): 531-546. doi:10.1074/jbc.RA118.006254. PMC 6333895. PMID 30446620.
  4. ^ a b c Alberts B, Lewis J, Raff M, Roberts K, Walter P (2002). Molecular biology of the cell (4th ed.). New York: Garland Science. ISBN 0-8153-3218-1.
  5. ^ Annala S, Feng X, Shridhar N, Eryilmaz F, Patt J, Yang J, Pfeil EM, Cervantes-Villagrana RD, Inoue A, Häberlein F, Slodczyk T, Reher R, Kehraus S, Monteleone S, Schrage R, Heycke N, Rick U, Engel S, Pfeifer A, Kolb P, König GM, Kostenis E, Bünemann M, Tüting T, Vázquez-Prado J, Gutkind JS, Gaffal E, Kostenis E (March 2019). "Direct Targeting of G?q and G?11 Oncoproteins in Cancer Cells". Sci Signal. 12 (573): 5948. doi:10.1126/scisignal.aau5948. PMID 30890659. S2CID 84183146.
  6. ^ a b Qin K, Dong C, Wu G, Lambert NA (August 2011). "Inactive-state preassembly of Gq-coupled receptors and Gq heterotrimers". Nature Chemical Biology. 7 (11): 740-747. doi:10.1038/nchembio.642. PMC 3177959. PMID 21873996.

External links


  This article uses material from the Wikipedia page available here. It is released under the Creative Commons Attribution-Share-Alike License 3.0.

Gq_alpha_subunit
 



 



 
Music Scenes