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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Delmas P, Crest M, Brown DA. Functional organization of PLC signaling microdomains in neurons. Trends Neurosci. 2004;27(1):41–7.
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.
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.
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.
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.
Gilman AG. G proteins: transducers of receptor-generated signals. Annu Rev Biochem. 1987;56:615–49.
Hein P, Bünemann M. Coupling mode of receptors and G proteins. Naunyn Schmiedeberg’s Arch Pharmacol. 2009;379(5):435–43.
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.
Lambert NA. Dissociation of heterotrimeric G proteins in cells. Sci Signal. 2008;1(25):re5.
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.
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.
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.
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.
Offermanns S. In vivo functions of heterotrimeric G-proteins: studies in Gα-deficient mice. Oncogene. 2001;20(13):1635–42.
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.
Ross EM. Coordinating speed and amplitude in G-protein signaling. Curr Biol. 2008;18(17):R777–83.
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.
Saini DK, Chisari M, Gautam N. Shuttling and translocation of heterotrimeric G proteins and Ras. Trends Pharmacol Sci. 2009;30(6):278–86.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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Falkenburger, B.H. (2018). G-Protein αq (GNAQ). In: Choi, S. (eds) Encyclopedia of Signaling Molecules. Springer, Cham. https://doi.org/10.1007/978-3-319-67199-4_351
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DOI: https://doi.org/10.1007/978-3-319-67199-4_351
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