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Gq alpha subunit

March 11, 2023

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, Gαq, or Gqα. Gq proteins couple to G protein-coupled receptors to activate beta-type phospholipase C (PLC-β) enzymes. PLC-β 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).

guanine nucleotide binding protein (G protein), q polypeptide
Identifiers
SymbolGNAQ
NCBI gene2776
HGNC4390
OMIM600998
RefSeqNM_002072
UniProtP50148
Other data
LocusChr. 9 q21
Search for
StructuresSwiss-model
DomainsInterPro
guanine nucleotide binding protein (G protein), alpha 11 (Gq class)
Identifiers
SymbolGNA11
NCBI gene2767
HGNC4379
OMIM139313
RefSeqNM_002067
UniProtP29992
Other data
LocusChr. 19 p13.3
Search for
StructuresSwiss-model
DomainsInterPro
guanine nucleotide binding protein (G protein), alpha 14
Identifiers
SymbolGNA14
NCBI gene9630
HGNC4382
OMIM604397
RefSeqNM_004297
UniProtO95837
Other data
LocusChr. 9 q21
Search for
StructuresSwiss-model
DomainsInterPro
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
Search for
StructuresSwiss-model
DomainsInterPro

Family members

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

  • Gαq is encoded by the gene GNAQ.
  • Gα11 is encoded by the gene GNA11.
  • Gα14 is encoded by the gene GNA14.
  • Gα15 is encoded by the gene GNA15.

Function

Main article: Heterotrimeric G protein

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 Gα protein such as Gαq, 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.

Gq/11/14/15 proteins all activate beta-type phospholipase C (PLC-β) to signal through calcium and PKC signaling pathways.[4] PLC-β 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 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 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.[7]

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). "Gβγ Signaling to the Chemotactic Effector P-REX1 and Mammalian Cell Migration Is Directly Regulated by Gαqand Gα13 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. ^ Onken MD, Makepeace CM, Kaltenbronn KM, Kanai SM, Todd TD, Wang S, Broekelmann TJ, Rao PK, Cooper JA, Blumer KJ (September 2018). "Targeting nucleotide exchange to inhibit constitutively active G protein alpha subunits in cancer cells". Sci Signal. 11 (546): 6852. doi:10.1126/scisignal.aao6852. PMC 6279241. PMID 30181242.
  6. ^ 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 Gαq and Gα11 Oncoproteins in Cancer Cells". Sci Signal. 12 (573): 5948. doi:10.1126/scisignal.aau5948. PMID 30890659. S2CID 84183146.
  7. ^ 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

March 11, 2023
alpha, subunit, protein, alpha, subunit, family, heterotrimeric, protein, alpha, subunits, this, family, also, commonly, called, family, family, include, closely, related, family, members, alpha, subunits, referred, alpha, gαq, gqα, proteins, couple, protein, . 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 Gaq or Gqa Gq proteins couple to G protein coupled receptors to activate beta type phospholipase C PLC b enzymes PLC b 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 guanine nucleotide binding protein G protein q polypeptideIdentifiersSymbolGNAQNCBI gene2776HGNC4390OMIM600998RefSeqNM 002072UniProtP50148Other dataLocusChr 9 q21Search forStructuresSwiss modelDomainsInterProguanine nucleotide binding protein G protein alpha 11 Gq class IdentifiersSymbolGNA11NCBI gene2767HGNC4379OMIM139313RefSeqNM 002067UniProtP29992Other dataLocusChr 19 p13 3Search forStructuresSwiss modelDomainsInterProguanine nucleotide binding protein G protein alpha 14IdentifiersSymbolGNA14NCBI gene9630HGNC4382OMIM604397RefSeqNM 004297UniProtO95837Other dataLocusChr 9 q21Search forStructuresSwiss modelDomainsInterProguanine nucleotide binding protein G protein alpha 15 Gq class IdentifiersSymbolGNA15NCBI gene2769HGNC4383OMIM139314RefSeqNM 002068UniProtP30679Other dataLocusChr 19 p13 3Search forStructuresSwiss modelDomainsInterPro Contents 1 Family members 2 Function 3 Receptors 4 See also 5 References 6 External linksFamily members EditIn humans there are four distinct proteins in the Gq alpha subunit family Gaq is encoded by the gene GNAQ Ga11 is encoded by the gene GNA11 Ga14 is encoded by the gene GNA14 Ga15 is encoded by the gene GNA15 Function EditMain article Heterotrimeric G protein 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 Ga protein such as Gaq and a complex of two tightly linked proteins called Gb and Gg in a Gbg complex 1 2 When not stimulated by a receptor Ga is bound to guanosine diphosphate GDP and to Gbg 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 Ga which drives dissociation of GTP bound Ga from Gbg 1 2 Recent evidence suggests that Gbg and Gaq GTP could maintain partial interaction via the N a helix region of Gaq 3 GTP bound Ga and Gbg are then freed to activate their respective downstream signaling enzymes Gq 11 14 15 proteins all activate beta type phospholipase C PLC b to signal through calcium and PKC signaling pathways 4 PLC b 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 vertebratesDAG 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 CThe Gaq Ga11 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 EditThe following G protein coupled receptors couple to Gq subunits 5 HT2 serotonergic receptors Alpha 1 adrenergic receptor Vasopressin type 1 receptors 1A and 1B Angiotensin II receptor type 1 Calcitonin receptor Histamine H1 receptor Metabotropic glutamate receptor Group I M1 M3 and M5 muscarinic receptors 7 Trace amine associated receptor 1At 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 7 See also EditSecond 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 subunitsReferences Edit 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 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 Cervantes Villagrana RD Adame Garcia SR Garcia Jimenez I Color Aparicio VM Beltran Navarro YM Konig GM Kostenis E Reyes Cruz G Gutkind JS Vazquez Prado J January 2019 Gbg Signaling to the Chemotactic Effector P REX1 and Mammalian Cell Migration Is Directly Regulated by Gaqand Ga13 Proteins J Biol Chem 294 2 531 546 doi 10 1074 jbc RA118 006254 PMC 6333895 PMID 30446620 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 Onken MD Makepeace CM Kaltenbronn KM Kanai SM Todd TD Wang S Broekelmann TJ Rao PK Cooper JA Blumer KJ September 2018 Targeting nucleotide exchange to inhibit constitutively active G protein alpha subunits in cancer cells Sci Signal 11 546 6852 doi 10 1126 scisignal aao6852 PMC 6279241 PMID 30181242 Annala S Feng X Shridhar N Eryilmaz F Patt J Yang J Pfeil EM Cervantes Villagrana RD Inoue A Haberlein F Slodczyk T Reher R Kehraus S Monteleone S Schrage R Heycke N Rick U Engel S Pfeifer A Kolb P Konig GM Kostenis E Bunemann M Tuting T Vazquez Prado J Gutkind JS Gaffal E Kostenis E March 2019 Direct Targeting of Gaq and Ga11 Oncoproteins in Cancer Cells Sci Signal 12 573 5948 doi 10 1126 scisignal aau5948 PMID 30890659 S2CID 84183146 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 EditGq protein at the US National Library of Medicine Medical Subject Headings MeSH Portal Biology Retrieved from https en wikipedia org w index php title Gq alpha subunit amp oldid 1113112906, wikipedia, wiki, book, books, library,

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