heterotrimeric gtp binding proteins


Summary: GTP-BINDING PROTEINS that contain three non-identical subunits. They are found associated with members of the seven transmembrane domain superfamily of G-PROTEIN-COUPLED RECEPTORS. Upon activation the GTP-BINDING PROTEIN ALPHA SUBUNIT of the complex dissociates leaving a dimer of a GTP-BINDING PROTEIN BETA SUBUNIT bound to a GTP-BINDING PROTEIN GAMMA SUBUNIT.

Top Publications

  1. Bellaiche Y, Gotta M. Heterotrimeric G proteins and regulation of size asymmetry during cell division. Curr Opin Cell Biol. 2005;17:658-63 pubmed
    ..Interestingly, recent work in mammalian cells suggests that heterotrimeric G proteins may control spindle positioning in higher organisms during symmetric and asymmetric cell divisions. ..
  2. Ohkuri T, Yasumatsu K, Horio N, Jyotaki M, Margolskee R, Ninomiya Y. Multiple sweet receptors and transduction pathways revealed in knockout mice by temperature dependence and gurmarin sensitivity. Am J Physiol Regul Integr Comp Physiol. 2009;296:R960-71 pubmed publisher
  3. McCudden C, Hains M, Kimple R, Siderovski D, Willard F. G-protein signaling: back to the future. Cell Mol Life Sci. 2005;62:551-77 pubmed
    ..Here, we revisit classical heterotrimeric G-protein signaling and explore these new, non-canonical G-protein signaling pathways. ..
  4. Lee H, Sung S, Han C, Kim Y, Kim S, Lee M, et al. G-protein beta3 subunit C825T polymorphism tends to be associated with seasonal variation in young male college students. Neuropsychobiology. 2005;52:135-9 pubmed
    ..These results suggest that GNB3 C825T polymorphism tends to be related to seasonal variation in mood and behavior in the normal population. ..
  5. Marrari Y, Crouthamel M, Irannejad R, Wedegaertner P. Assembly and trafficking of heterotrimeric G proteins. Biochemistry. 2007;46:7665-77 pubmed
    ..Understanding G protein assembly and trafficking will lead to a greater understanding of novel ways that cells regulate G protein signaling. ..
  6. de Vries D, Ter Linde J, van Herwaarden M, Smout A, Samsom M. Gastroesophageal reflux disease is associated with the C825T polymorphism in the G-protein beta3 subunit gene (GNB3). Am J Gastroenterol. 2009;104:281-5 pubmed publisher
    ..The results for GERD subgroups support the hypothesis that enhanced perception of reflux events, as a consequence of the increased signal transduction upon GPCR activation associated with the 825T allele, underlies this association. ..
  7. Schurks M, Kurth T, Stude P, Rimmbach C, De Jesus J, Jonjic M, et al. G protein beta3 polymorphism and triptan response in cluster headache. Clin Pharmacol Ther. 2007;82:396-401 pubmed
    ..e., drugs not directly affecting G proteins. We conclude that pain relief by triptans is significantly modulated by a common genetic GNB3 variant. ..
  8. Oldham W, Hamm H. Heterotrimeric G protein activation by G-protein-coupled receptors. Nat Rev Mol Cell Biol. 2008;9:60-71 pubmed
  9. Tahara T, Arisawa T, Shibata T, Wang F, Nakamura M, Sakata M, et al. Homozygous 825T allele of the GNB3 protein influences the susceptibility of Japanese to dyspepsia. Dig Dis Sci. 2008;53:642-6 pubmed
    ..Our data suggest that the homozygous 825T allele of GNB3 protein is associated with dyspepsia in the H. pylori-negative Japanese population. The role of genetics in the development of dyspepsia needs further evaluation. ..

More Information


  1. Digby G, Sethi P, Lambert N. Differential dissociation of G protein heterotrimers. J Physiol. 2008;586:3325-35 pubmed publisher
    ..Differential dissociation may thus provide a simple explanation for G alpha-specific activation of GIRK channels and other G betagamma-sensitive effectors. ..
  2. Tizzano M, Dvoryanchikov G, Barrows J, Kim S, Chaudhari N, Finger T. Expression of Galpha14 in sweet-transducing taste cells of the posterior tongue. BMC Neurosci. 2008;9:110 pubmed publisher
    ..Galpha14 is co-expressed with the sweet taste receptor in posterior tongue, although not in anterior tongue. Thus, sweet taste transduction may rely on different downstream transduction elements in posterior and anterior taste fields. ..
  3. Johnston C, Taylor J, Gao Y, Kimple A, Grigston J, Chen J, et al. GTPase acceleration as the rate-limiting step in Arabidopsis G protein-coupled sugar signaling. Proc Natl Acad Sci U S A. 2007;104:17317-22 pubmed
  4. Muller D, De Luca V, Sicard T, King N, Hwang R, Volavka J, et al. Suggestive association between the C825T polymorphism of the G-protein beta3 subunit gene (GNB3) and clinical improvement with antipsychotics in schizophrenia. Eur Neuropsychopharmacol. 2005;15:525-31 pubmed
    ..8 to 7%. Our results further suggest that this effect is only attributable to Caucasians when compared to African-Americans. Moreover, our findings point to the role of intracellular mechanisms in antipsychotic response. ..
  5. Znoiko S, Rohrer B, Lu K, Lohr H, Crouch R, Ma J. Downregulation of cone-specific gene expression and degeneration of cone photoreceptors in the Rpe65-/- mouse at early ages. Invest Ophthalmol Vis Sci. 2005;46:1473-9 pubmed
    ..Early administration of 9- or 11-cis retinal can partially prevent cone loss, suggesting that the absence of 11-cis chromophore may be responsible for the early cone degeneration. ..
  6. Yanamadala V, Negoro H, Denker B. Heterotrimeric G proteins and apoptosis: intersecting signaling pathways leading to context dependent phenotypes. Curr Mol Med. 2009;9:527-45 pubmed
    ..Continued investigation in this field is essential for the identification of important targets for pharmacological intervention in numerous diseases. ..
  7. Nilson S, Assmann S. Heterotrimeric G proteins regulate reproductive trait plasticity in response to water availability. New Phytol. 2010;185:734-46 pubmed publisher
  8. Wang H, Ng K, Qian H, Siderovski D, Chia W, Yu F. Ric-8 controls Drosophila neural progenitor asymmetric division by regulating heterotrimeric G proteins. Nat Cell Biol. 2005;7:1091-8 pubmed
    ..In addition, Gbetagamma acts to restrict Galphai (and GoLoco proteins) to the apical cortex, where Galphai (and Pins) can mediate asymmetric spindle geometry. ..
  9. Trusov Y, Rookes J, Chakravorty D, Armour D, Schenk P, Botella J. Heterotrimeric G proteins facilitate Arabidopsis resistance to necrotrophic pathogens and are involved in jasmonate signaling. Plant Physiol. 2006;140:210-20 pubmed
    ..We hypothesize that Gbetagamma acts as a direct or indirect enhancer of the jasmonate signaling pathway in plants. ..
  10. Bavec A. Novel features of amphiphilic peptide Mas7 in signalling via heterotrimeric G-proteins. J Pept Sci. 2004;10:691-9 pubmed
    ..In conclusion, the signal is mediated from Mas7 to endogenous mono-ADP-ribosyltransferase via pertussis sensitive G-proteins. Furthermore, it is hypothesized that Gi2 G-proteins are not involved in the process. ..
  11. Du Q, Macara I. Mammalian Pins is a conformational switch that links NuMA to heterotrimeric G proteins. Cell. 2004;119:503-16 pubmed
    ..We propose that a related switch mechanism might operate in asymmetric cell divisions in the fly and nematode. ..
  12. Chen J, Gao Y, Jones A. Differential roles of Arabidopsis heterotrimeric G-protein subunits in modulating cell division in roots. Plant Physiol. 2006;141:887-97 pubmed
    ..These results suggest that Arabidopsis heterotrimeric G-protein subunits have differential and opposing roles in the modulation of cell division in roots. ..
  13. Bavec A, Jiang Y, Langel U, Zorko M. Role of cysteine 341 and arginine 348 of GLP-1 receptor in G-protein coupling. Mol Biol Rep. 2007;34:53-60 pubmed
    ..Moreover, these two amino acids from the third intracellular loop might represent an important novel targets for covalent modification by downstream regulators in signaling through GLP-1 receptor. ..
  14. Siderovski D, Willard F. The GAPs, GEFs, and GDIs of heterotrimeric G-protein alpha subunits. Int J Biol Sci. 2005;1:51-66 pubmed
    ..Discovery of these novel GAP, GDI, and GEF activities have helped to illuminate a new role for Galpha subunit GDP/GTP cycling required for microtubule force generation and mitotic spindle function in chromosomal segregation. ..
  15. Perfus Barbeoch L, Jones A, Assmann S. Plant heterotrimeric G protein function: insights from Arabidopsis and rice mutants. Curr Opin Plant Biol. 2004;7:719-31 pubmed
    ..Results and concepts emerging from recent phenotypic analyses of G-protein component mutants in Arabidopsis and rice are adding to our understanding of G-protein mechanisms and functions in higher plants. ..
  16. Temple B, Jones A. The plant heterotrimeric G-protein complex. Annu Rev Plant Biol. 2007;58:249-66 pubmed
    ..This review addresses these unique features and speculates on why the repertoire of G-protein signaling elements is dramatically simpler than that in all other multicellular eukaryotes. ..
  17. Shindo Y, Miura H, Carninci P, Kawai J, Hayashizaki Y, Ninomiya Y, et al. G alpha14 is a candidate mediator of sweet/umami signal transduction in the posterior region of the mouse tongue. Biochem Biophys Res Commun. 2008;376:504-8 pubmed publisher
    ..G alpha14 was co-expressed with T1r3, a sweet/umami taste receptor, but not with gustducin in CV. These results suggest the important roles of G alpha14 in sweet/umami taste signal transduction in the posterior region of the tongue. ..
  18. Suwazono Y, Kobayashi E, Uetani M, Miura K, Morikawa Y, Ishizaki M, et al. G-protein beta3 subunit variant C825T is a risk factor for hypertension in Japanese females--a prospective cohort study over 5 years. Ann Hum Genet. 2006;70:767-77 pubmed
  19. Matsunaga T, Nagasumi K, Yamamura T, Gu N, Nishikino M, Ueda Y, et al. Association of C825T polymorphism of G protein beta3 subunit with the autonomic nervous system in young healthy Japanese individuals. Am J Hypertens. 2005;18:523-9 pubmed
    ..These findings raise the possibility that individuals who are T allele carriers are at increased risk for developing hypertension in relation to ANS function. ..
  20. Wang S, Narendra S, Fedoroff N. Heterotrimeric G protein signaling in the Arabidopsis unfolded protein response. Proc Natl Acad Sci U S A. 2007;104:3817-22 pubmed
  21. Assmann S. G proteins Go green: a plant G protein signaling FAQ sheet. Science. 2005;310:71-3 pubmed
    ..Pathways in Science's Signal Transduction Knowledge Environment Connections Maps database provide details about the emerging roles of G proteins in several cellular processes of plants. ..
  22. Johnston C, Siderovski D. Receptor-mediated activation of heterotrimeric G-proteins: current structural insights. Mol Pharmacol. 2007;72:219-30 pubmed
    ..We highlight several recent results shedding new light on the structural changes in Galpha that may underlie GDP release. ..
  23. Wolfe J, Wang H, Howard J, Garrison J, Barrett P. T-type calcium channel regulation by specific G-protein betagamma subunits. Nature. 2003;424:209-13 pubmed
    ..These studies identify the alpha1H channel as a new effector for G-protein betagamma subunits, and highlight the selective signalling roles available for particular betagamma combinations. ..
  24. Grill S, Howard J, Schäffer E, Stelzer E, Hyman A. The distribution of active force generators controls mitotic spindle position. Science. 2003;301:518-21 pubmed
    ..Moreover, activation of heterotrimeric guanine nucleotide- binding protein (Gprotein) alpha subunits is required to generate these astral forces. ..
  25. Ueda T, Ugawa S, Yamamura H, Imaizumi Y, Shimada S. Functional interaction between T2R taste receptors and G-protein alpha subunits expressed in taste receptor cells. J Neurosci. 2003;23:7376-80 pubmed
    ..The present Galpha16-based chimeras could be useful tools to analyze the functions of many orphan G-protein-coupled taste receptors. ..
  26. Lee H, Cha J, Ham B, Han C, Kim Y, Lee S, et al. Association between a G-protein beta 3 subunit gene polymorphism and the symptomatology and treatment responses of major depressive disorders. Pharmacogenomics J. 2004;4:29-33 pubmed
    ..It was also demonstrated that MDD patients bearing the T allele had a severe symptomatology and a better response to antidepressant treatment than patients without the T allele. ..
  27. Jones A, Assmann S. Plants: the latest model system for G-protein research. EMBO Rep. 2004;5:572-8 pubmed
    ..Nonetheless, recent studies on Arabidopsis thaliana have shown the importance of plant G-protein signalling in such fundamental processes as cell proliferation, hormone perception and ion-channel regulation. ..
  28. Ma H, Peterson Y, Bernard M, Lanier S, Graber S. Influence of cytosolic AGS3 on receptor--G protein coupling. Biochemistry. 2003;42:8085-93 pubmed
    ..These findings suggest that AGS3 may downregulate heterotrimeric G protein signaling by interfering with receptor coupling. ..
  29. Ghosh M, Peterson Y, Lanier S, Smrcka A. Receptor- and nucleotide exchange-independent mechanisms for promoting G protein subunit dissociation. J Biol Chem. 2003;278:34747-50 pubmed
  30. Willard F, Siderovski D. Purification and in vitro functional analysis of the Arabidopsis thaliana regulator of G-protein signaling-1. Methods Enzymol. 2004;389:320-38 pubmed
    ..This article describes methods for the purification and in vitro functional analysis of the RGS box of AtRGS1. ..
  31. Ishii M, Kurachi Y. Assays of RGS protein modulation by phosphatidylinositides and calmodulin. Methods Enzymol. 2004;389:105-18 pubmed
    ..These assays would be useful for dissecting the physiological modes of action of RGS proteins in controlling G-protein-mediated signaling machinery. ..
  32. Iacovelli L, Capobianco L, Iula M, Di Giorgi Gerevini V, Picascia A, Blahos J, et al. Regulation of mGlu4 metabotropic glutamate receptor signaling by type-2 G-protein coupled receptor kinase (GRK2). Mol Pharmacol. 2004;65:1103-10 pubmed
    ..We speculate that GRK2 acts as a "switch molecule" by inhibiting the mGlu4 receptor-mediated stimulation of MAPK and therefore directing the signal propagation toward the inhibition of adenylyl cyclase. ..
  33. Jones M, Siderovski D, Hooks S. The G betagamma dimer as a novel source of selectivity in G-protein signaling: GGL-ing at convention. Mol Interv. 2004;4:200-14 pubmed
  34. Holtmann G, Siffert W, Haag S, Mueller N, Langkafel M, Senf W, et al. G-protein beta 3 subunit 825 CC genotype is associated with unexplained (functional) dyspepsia. Gastroenterology. 2004;126:971-9 pubmed
    ..2 (95% confidence interval [CI]: 1.4-3.3), compared with subjects with TC and TT genotype carrying an allele. Homozygous GNB3 825C carrier status is associated with unexplained predominantly upper abdominal symptoms. ..
  35. Van Haastert P, Devreotes P. Chemotaxis: signalling the way forward. Nat Rev Mol Cell Biol. 2004;5:626-34 pubmed
    ..Recent studies are beginning to identify an intricate network of signalling molecules that mediate these processes, and how these molecules become localized in the cell is now becoming clear. ..
  36. Hess H, Röper J, Grill S, Koelle M. RGS-7 completes a receptor-independent heterotrimeric G protein cycle to asymmetrically regulate mitotic spindle positioning in C. elegans. Cell. 2004;119:209-18 pubmed
    ..While GTPase activators typically inactivate G proteins, RGS-7 instead appears to promote G protein function asymmetrically in the cell, perhaps acting as a G protein effector. ..
  37. Thibaudin L, Berthoux P, Thibaudin D, Mariat C, Berthoux F. G protein beta3 subunit C825T polymorphism in primary IgA nephropathy. Kidney Int. 2004;66:322-8 pubmed
    ..The C825T GNB3 polymorphism had a mild influence on occurrence/initiation of IgAN, but played no significant role in the progression of the disease. ..
  38. Chen J, Willard F, Huang J, Liang J, Chasse S, Jones A, et al. A seven-transmembrane RGS protein that modulates plant cell proliferation. Science. 2003;301:1728-31 pubmed
    ..These findings suggest that AtRGS1 is a critical modulator of plant cell proliferation. ..
  39. Zhao J, Wang X. Arabidopsis phospholipase Dalpha1 interacts with the heterotrimeric G-protein alpha-subunit through a motif analogous to the DRY motif in G-protein-coupled receptors. J Biol Chem. 2004;279:1794-800 pubmed
  40. Kimple R, Willard F, Siderovski D. The GoLoco motif: heralding a new tango between G protein signaling and cell division. Mol Interv. 2002;2:88-100 pubmed
    ..Such peptides could be exploited to help dissect the signals that underpin cell polarity and cell division processes. ..
  41. Kitanaka N, Kitanaka J, Walther D, Wang X, Uhl G. Comparative inter-strain sequence analysis of the putative regulatory region of murine psychostimulant-regulated gene GNB1 (G protein beta 1 subunit gene). DNA Seq. 2003;14:257-63 pubmed
  42. Matayoshi T, Kamide K, Takiuchi S, Yoshii M, Miwa Y, Takami Y, et al. The thiazide-sensitive Na(+)-Cl(-) cotransporter gene, C1784T, and adrenergic receptor-beta3 gene, T727C, may be gene polymorphisms susceptible to the antihypertensive effect of thiazide diuretics. Hypertens Res. 2004;27:821-33 pubmed
    ..Both newly detected TSC C1784T and ADRB3 T727C are gene polymorphisms susceptible to the antihypertensive effect of TZDs in patients with EHT. Thus, the prediction of BP reduction by TZDs may be possible by evaluating these two SNPs. ..
  43. Lelonek M, Pietrucha T, Matyjaszczyk M, Goch J. Genetic insight into syncopal tilted population with severe clinical presentation. Auton Neurosci. 2009;147:97-100 pubmed publisher
    ..05). The studied single nucleotide polymorphisms of genes encoding G-proteins signaling pathways seem to be not connected with the severe clinical manifestation of syncope. ..
  44. Albarrán Juárez J, Gilsbach R, Piekorz R, Pexa K, Beetz N, Schneider J, et al. Modulation of alpha2-adrenoceptor functions by heterotrimeric Galphai protein isoforms. J Pharmacol Exp Ther. 2009;331:35-44 pubmed publisher
    ..In contrast, inhibition of locomotor activity and anesthetic sparing may be elicited by a specific coupling of alpha(2A)-adrenoceptors via the Galpha(i2) isoform to intracellular pathways. ..
  45. Schelleman H, Stricker B, Verschuren W, de Boer A, Kroon A, de Leeuw P, et al. Interactions between five candidate genes and antihypertensive drug therapy on blood pressure. Pharmacogenomics J. 2006;6:22-6 pubmed
    ..33 mmHg [95% CI: 0.14-8.54]). Thus, the mean SBP level among diuretic users may be modified by the GNB3 825C/T polymorphism. ..
  46. Sorrentino S, Forleo C, Iacoviello M, Guida P, D Andria V, Favale S. Lack of association between genetic polymorphisms affecting sympathetic activity and tilt-induced vasovagal syncope. Auton Neurosci. 2010;155:98-103 pubmed publisher
    ..None of the considered polymorphisms influencing sympathetic activity is a major risk factor for vasovagal syncope in Italian patients...
  47. Palma Nicolas J, Lopez E, López Colomé A. PKC isoenzymes differentially modulate the effect of thrombin on MAPK-dependent RPE proliferation. Biosci Rep. 2008;28:307-17 pubmed publisher
    ..The present study is the first report demonstrating directly thrombin-induced ERK phosphorylation in the RPE, and the involvement of atypical PKCzeta in this process. ..
  48. Egger Adam D, Katanaev V. Trimeric G protein-dependent signaling by Frizzled receptors in animal development. Front Biosci. 2008;13:4740-55 pubmed
    ..Other structural and functional similarities of Frizzled receptors and the GPCRs are also discussed. ..
  49. Bishop J, Ellingrod V, Moline J, Miller D. Pilot study of the G-protein beta3 subunit gene (C825T) polymorphism and clinical response to olanzapine or olanzapine-related weight gain in persons with schizophrenia. Med Sci Monit. 2006;12:BR47-50 pubmed
  50. Kang R, Hahn S, Choi M, Lee M. Relationship between G-protein beta-3 subunit C825T polymorphism and mirtazapine responses in Korean patients with major depression. Neuropsychobiology. 2007;56:1-5 pubmed
    ..Although the C825T polymorphism of the GNB3 gene may affect the pathogenesis of MDD, our results do not support the hypothesis that this polymorphism is involved in the therapeutic response to mirtazapine in Korean patients with MDD. ..
  51. Preininger A, Henage L, Oldham W, Yoon E, Hamm H, Brown H. Direct modulation of phospholipase D activity by Gbetagamma. Mol Pharmacol. 2006;70:311-8 pubmed
    ..These data demonstrate that Gbetagamma directly regulates phospholipase D activity in vitro and suggest a novel mechanism to negatively regulate phospholipase D signaling in vivo. ..
  52. Dave R, Saengsawang W, Yu J, Donati R, Rasenick M. Heterotrimeric G-proteins interact directly with cytoskeletal components to modify microtubule-dependent cellular processes. Neurosignals. 2009;17:100-8 pubmed publisher
    ..Further studies are needed to fully establish a structural mechanism of this interaction and its role in synaptic plasticity. ..
  53. Pitsavos C, Papadimitriou L, Panagiotakos D, Chrysohoou C, Skoumas J, Dedoussis G, et al. Lack of association between the C825T polymorphism in G-protein beta-3 subunit and arterial blood pressure levels in cardiovascular disease free individuals: the ATTICA epidemiological study. J Hum Hypertens. 2006;20:303-5 pubmed