Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi

G-Protein αq (GNAQ)

  • Björn H. FalkenburgerEmail author
Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_351


Historical Background

Hormone receptors elicit cellular responses most often not directly, but through diffusible second messengers. In the early 1970s it was found that second messenger synthesis requires guanosine triphosphate (GTP). Yet, GTP binds neither to hormone receptors nor to enzyme effectors. Instead, GTP binds to GTP-sensitive transducers (see Gilman 1987). These G-proteins are heterotrimers of α, β, and γ subunits. The first Gα subunits to be identified were Gαs, and transducin. Gαs triggers the formation of cAMP. Transducin mediates the effects of rhodopsin. Signaling by Gαs was found sensitive to pertussis toxin. Signaling by Gαi, which inhibits cAMP formation, was found sensitive to cholera toxin. Formation of the second messengers inositol trisphosphate (IP3) and diacylglycerol (DAG) by...

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  1. Delmas P, Crest M, Brown DA. Functional organization of PLC signaling microdomains in neurons. Trends Neurosci. 2004;27(1):41–7.PubMedCrossRefGoogle Scholar
  2. Dong Q, Shenker A, Way J, Haddad BR, Lin K, Hughes MR, et al. Molecular cloning of human Gαq cDNA and chromosomal localization of the Gαq gene (GNAQ) and a processed pseudogene. Genomics. 1995;30(3):470–5.PubMedCrossRefGoogle Scholar
  3. Falkenburger BH, Jensen JB, Hille B. Kinetics of M1 muscarinic receptor and G protein signaling to phospholipase C in living cells. J Gen Physiol. 2010;135(2):81–97.PubMedPubMedCentralCrossRefGoogle Scholar
  4. Feng X, Degese MS, Iglesias-Bartolome R, Vaque JP, Molinolo AA, Rodrigues M, et al. Hippo-independent activation of YAP by the GNAQ uveal melanoma oncogene through a trio-regulated rho GTPase signaling circuitry. Cancer Cell. 2014;25(6):831–45.PubMedPubMedCentralCrossRefGoogle Scholar
  5. Frederick AL, Saborido TP, Stanwood GD. Neurobehavioral phenotyping of G(αq) knockout mice reveals impairments in motor functions and spatial working memory without changes in anxiety or behavioral despair. Front Behav Neurosci. 2012;6:29.PubMedPubMedCentralCrossRefGoogle Scholar
  6. Gilman AG. G proteins: transducers of receptor-generated signals. Annu Rev Biochem. 1987;56:615–49.PubMedCrossRefGoogle Scholar
  7. Hein P, Bünemann M. Coupling mode of receptors and G proteins. Naunyn Schmiedeberg’s Arch Pharmacol. 2009;379(5):435–43.CrossRefGoogle Scholar
  8. Jensen JB, Lyssand JS, Hague C, Hille B. Fluorescence changes reveal kinetic steps of muscarinic receptor-mediated modulation of phosphoinositides and Kv7.2/7.3 K + channels. J Gen Physiol. 2009;133(4):347–59.PubMedPubMedCentralCrossRefGoogle Scholar
  9. Lambert NA. Dissociation of heterotrimeric G proteins in cells. Sci Signal. 2008;1(25):re5.PubMedCrossRefGoogle Scholar
  10. Liu Y, Wang D, Li F, Shi G. Gαq controls rheumatoid arthritis via regulation of Th17 differentiation. Immunol Cell Biol. 2015;93(7):616–24.PubMedCrossRefGoogle Scholar
  11. Lohse MJ, Hein P, Hoffmann C, Nikolaev VO, Vilardaga J-P, Bünemann M. Kinetics of G-protein-coupled receptor signals in intact cells. Br J Pharmacol. 2008;153(Suppl 1):S125–32.PubMedPubMedCentralGoogle Scholar
  12. Ma YC, Huang XY. Identification of the binding site for Gqα on its effector Bruton’s tyrosine kinase. Proc Natl Acad Sci U S A. 1998;95(21):12197–201.PubMedPubMedCentralCrossRefGoogle Scholar
  13. Nishimura A, Kitano K, Takasaki J, Taniguchi M, Mizuno N, Tago K, et al. Structural basis for the specific inhibition of heterotrimeric G q protein by a small molecule. Proc Natl Acad Sci USA. 2010;107(31):13666–71.PubMedPubMedCentralCrossRefGoogle Scholar
  14. Offermanns S. In vivo functions of heterotrimeric G-proteins: studies in Gα-deficient mice. Oncogene. 2001;20(13):1635–42.PubMedCrossRefGoogle Scholar
  15. Rojas RJ, Yohe ME, Gershburg S, Kawano T, Kozasa T, Sondek J. Gαq directly activates p63RhoGEF and Trio via a conserved extension of the Dbl homology-associated pleckstrin homology domain. J Biol Chem. 2007;282(40):29201–10.PubMedPubMedCentralCrossRefGoogle Scholar
  16. Ross EM. Coordinating speed and amplitude in G-protein signaling. Curr Biol. 2008;18(17):R777–83.PubMedPubMedCentralCrossRefGoogle Scholar
  17. Ross EM, Wilkie TM. GTPase-activating proteins for heterotrimeric G proteins: regulators of G protein signaling (RGS) and RGS-like proteins. Annu Rev Biochem. 2000;69:795–827.PubMedCrossRefGoogle Scholar
  18. Saini DK, Chisari M, Gautam N. Shuttling and translocation of heterotrimeric G proteins and Ras. Trends Pharmacol Sci. 2009;30(6):278–86.PubMedPubMedCentralCrossRefGoogle Scholar
  19. Shirley MD, Tang H, Gallione CJ, Baugher JD, Frelin LP, Cohen B, et al. Sturge-Weber syndrome and port-wine stains caused by somatic mutation in GNAQ. N Engl J Med. 2013;368(21):1971–9.PubMedPubMedCentralCrossRefGoogle Scholar
  20. Strathmann M, Simon MI. G protein diversity: a distinct class of α subunits is present in vertebrates and invertebrates. Proc Natl Acad Sci USA. 1990;87(23):9113–7.PubMedPubMedCentralCrossRefGoogle Scholar
  21. Tsutsumi R, Fukata Y, Noritake J, Iwanaga T, Perez F, Fukata M. Identification of G protein α subunit-palmitoylating enzyme. Mol Cell Biol. 2009;29(2):435–47.PubMedCrossRefGoogle Scholar
  22. Van Raamsdonk CD, Bezrookove V, Green G, Bauer J, Gaugler L, O’Brien JM, et al. Frequent somatic mutations of GNAQ in uveal melanoma and blue naevi. Nature. 2009;457(7229):599–602.PubMedCrossRefGoogle Scholar
  23. Vaque JP, Dorsam RT, Feng X, Iglesias-Bartolome R, Forsthoefel DJ, Chen Q, et al. A genome-wide RNAi screen reveals a Trio-regulated Rho GTPase circuitry transducing mitogenic signals initiated by G protein-coupled receptors. Mol Cell. 2013;49(1):94–108.PubMedCrossRefGoogle Scholar
  24. Wilkie TM, Gilbert DJ, Olsen AS, Chen XN, Amatruda TT, Korenberg JR, et al. Evolution of the mammalian G protein α subunit multigene family. Nat Genet. 1992;1(2):85–91.PubMedCrossRefGoogle Scholar
  25. Yoo JH, Shi DS, Grossmann AH, Sorensen LK, Tong Z, Mleynek TM, et al. ARF6 Is an Actionable Node that Orchestrates Oncogenic GNAQ Signaling in Uveal Melanoma. Cancer Cell. 2016;29(6):889–904.PubMedPubMedCentralCrossRefGoogle Scholar
  26. Yu F-X, Luo J, Mo J-S, Liu G, Kim YC, Meng Z, et al. Mutant Gq/11 promote uveal melanoma tumorigenesis by activating YAP. Cancer Cell. 2014;25(6):822–30.PubMedPubMedCentralCrossRefGoogle Scholar
  27. Yuan C, Sato M, Lanier SM, Smrcka AV. Signaling by a non-dissociated complex of G protein βγ and α subunits stimulated by a receptor-independent activator of G protein signaling, AGS8. J Biol Chem. 2007;282(27):19938–47.PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Department of NeurologyRWTH University Medical CenterAachenGermany