gq g11 gtp binding protein alpha subunits


Summary: A family of heterotrimeric GTP-binding protein alpha subunits that activate TYPE C PHOSPHOLIPASES dependent signaling pathways. The Gq-G11 part of the name is also spelled Gq/G11.

Top Publications

  1. Shi G, Partida Sanchez S, Misra R, Tighe M, Borchers M, Lee J, et al. Identification of an alternative G{alpha}q-dependent chemokine receptor signal transduction pathway in dendritic cells and granulocytes. J Exp Med. 2007;204:2705-18 pubmed
  2. Ballou L, Chattopadhyay M, Li Y, Scarlata S, Lin R. Galphaq binds to p110alpha/p85alpha phosphoinositide 3-kinase and displaces Ras. Biochem J. 2006;394:557-62 pubmed
    ..These results suggest that activation of G(q)-coupled receptors leads to increased binding of Galpha(q).GTP to some isoforms of PI3K, which might explain why these receptors inhibit this signalling pathway in certain cell types. ..
  3. Liao Z, Seye C, Weisman G, Erb L. The P2Y2 nucleotide receptor requires interaction with alpha v integrins to access and activate G12. J Cell Sci. 2007;120:1654-62 pubmed
  4. Brown S, Jala V, Raghuwanshi S, Nasser M, Haribabu B, Richardson R. Activation and regulation of platelet-activating factor receptor: role of G(i) and G(q) in receptor-mediated chemotactic, cytotoxic, and cross-regulatory signals. J Immunol. 2006;177:3242-9 pubmed
    ..Because chemotaxis and cross-desensitization are exclusively mediated by G(i), the data suggest that differential activation of both G(i) and G(q) by PAFR likely mediate specific as well as redundant signaling pathways. ..
  5. Howes A, Miyamoto S, Adams J, Woodcock E, Brown J. Galphaq expression activates EGFR and induces Akt mediated cardiomyocyte survival: dissociation from Galphaq mediated hypertrophy. J Mol Cell Cardiol. 2006;40:597-604 pubmed
    ..These data demonstrate that increased Galphaq activity can provide anti-apoptotic signals by eliciting EGFR phosphorylation and subsequent Akt activation, independent of the well-known ability of Galphaq signaling to elicit hypertrophy. ..
  6. Ngai J, Methi T, Andressen K, Levy F, Torgersen K, Vang T, et al. The heterotrimeric G-protein alpha-subunit Galphaq regulates TCR-mediated immune responses through an Lck-dependent pathway. Eur J Immunol. 2008;38:3208-18 pubmed publisher
    ..Together these data argue for a role of Galphaq in the fine-tuning of proximal TCR signals at the level of Lck and a negative regulatory role of Galphaq in transcriptional activation of cytokine responses. ..
  7. Roberts Crowley M, Mitra Ganguli T, Liu L, Rittenhouse A. Regulation of voltage-gated Ca2+ channels by lipids. Cell Calcium. 2009;45:589-601 pubmed publisher
    ..This unexpectedly simple scheme gives rise to unanticipated predictions and redirects thinking about lipid regulation of VGCCs. ..
  8. Atkinson P, Young K, Ennion S, Kew J, Nahorski S, Challiss R. Altered expression of G(q/11alpha) protein shapes mGlu1 and mGlu5 receptor-mediated single cell inositol 1,4,5-trisphosphate and Ca(2+) signaling. Mol Pharmacol. 2006;69:174-84 pubmed
    ..These experiments indicate that altering G(q/11)alpha expression levels differentially affects spatiotemporal aspects of IP(3) and Ca(2+) signaling mediated by the mGlu1 and mGlu5 receptors. ..
  9. Hildebrand M, David L, Hamid J, Mulatz K, Garcia E, Zamponi G, et al. Selective inhibition of Cav3.3 T-type calcium channels by Galphaq/11-coupled muscarinic acetylcholine receptors. J Biol Chem. 2007;282:21043-55 pubmed
    ..3 channel are necessary and sufficient for complete M1 receptor-mediated channel inhibition and represent novel sites not previously implicated in T-type channel modulation. ..

More Information


  1. Wang P, DeFea K. Protease-activated receptor-2 simultaneously directs beta-arrestin-1-dependent inhibition and Galphaq-dependent activation of phosphatidylinositol 3-kinase. Biochemistry. 2006;45:9374-85 pubmed
  2. Uemura T, Takamatsu H, Kawasaki T, Taniguchi M, Yamamoto E, Tomura Y, et al. Effect of YM-254890, a specific Galphaq/11 inhibitor, on experimental peripheral arterial disease in rats. Eur J Pharmacol. 2006;536:154-61 pubmed
    ..These results suggest that the local administration of YM-254890 may be useful for treating peripheral arterial disease. ..
  3. Onken M, Worley L, Long M, Duan S, Council M, Bowcock A, et al. Oncogenic mutations in GNAQ occur early in uveal melanoma. Invest Ophthalmol Vis Sci. 2008;49:5230-4 pubmed publisher
    ..Mutations in this G-protein-coupled receptor provide new insights into UM pathogenesis and could lead to new therapeutic possibilities. ..
  4. Golebiewska U, Scarlata S. Galphaq binds two effectors separately in cells: evidence for predetermined signaling pathways. Biophys J. 2008;95:2575-82 pubmed publisher
    ..Preformed G-protein/effector complexes will limit the number of pathways that a given signal will take, which may simplify predictive models. ..
  5. Fang Y, Li G, Peng J. Optical biosensor provides insights for bradykinin B(2) receptor signaling in A431 cells. FEBS Lett. 2005;579:6365-74 pubmed
    ..The roles of endocytosis and cytoskeleton modulation in B(2) signaling were also demonstrated. ..
  6. Hubbard K, Hepler J. Cell signalling diversity of the Gqalpha family of heterotrimeric G proteins. Cell Signal. 2006;18:135-50 pubmed
    ..Taken together, these findings demonstrate that Gqalpha, G11alpha, G14alpha and G15/16alpha regulate both overlapping and distinct signalling pathways, indicating that they are more functionally diverse than previously thought. ..
  7. Goon Goh F, Sloss C, Cunningham M, Nilsson M, Cadalbert L, Plevin R. G-protein-dependent and -independent pathways regulate proteinase-activated receptor-2 mediated p65 NFkappaB serine 536 phosphorylation in human keratinocytes. Cell Signal. 2008;20:1267-74 pubmed publisher
    ..Overall these novel data demonstrate an IKK2-dependent, predominantly G-protein-independent pathway involved in PAR-2 regulation of NFkappaB phosphorylation in keratinocytes. ..
  8. Brem R, Storey J, Whittle J, Kruglyak L. Genetic interactions between polymorphisms that affect gene expression in yeast. Nature. 2005;436:701-3 pubmed
    ..Our results indicate that genetic interactions are widespread in the genetics of transcript levels, and that many QTLs will be missed by single-locus tests but can be detected by two-stage tests that allow for interactions. ..
  9. Taboubi S, Milanini J, Delamarre E, Parat F, Garrouste F, Pommier G, et al. G alpha(q/11)-coupled P2Y2 nucleotide receptor inhibits human keratinocyte spreading and migration. FASEB J. 2007;21:4047-58 pubmed
    ..Collectively, these findings provide evidence for a unique and important role for extracellular nucleotides as efficient autocrine/paracrine regulators of keratinocyte shape and migration during wound healing. ..
  10. Frey U, Lieb W, Erdmann J, Savidou D, Heusch G, Leineweber K, et al. Characterization of the GNAQ promoter and association of increased Gq expression with cardiac hypertrophy in humans. Eur Heart J. 2008;29:888-97 pubmed publisher
    ..52; P = 0.005). A novel polymorphism in the Gq promoter region is associated with enhanced promoter activity, Gq expression, intracellular signal transduction, and increased prevalence of LVH, particularly in women. ..
  11. Rojas R, Yohe M, Gershburg S, Kawano T, Kozasa T, Sondek J. Galphaq directly activates p63RhoGEF and Trio via a conserved extension of the Dbl homology-associated pleckstrin homology domain. J Biol Chem. 2007;282:29201-10 pubmed
    ..This unique extension is conserved in the related Dbl-family members Trio and Kalirin and we show that the C-terminal Rho-specific DH-PH cassette of Trio is similarly activated by Galpha(q). ..
  12. Meza U, Thapliyal A, Bannister R, Adams B. Neurokinin 1 receptors trigger overlapping stimulation and inhibition of CaV2.3 (R-type) calcium channels. Mol Pharmacol. 2007;71:284-93 pubmed
    ..This new information concerning R-type calcium channels and NK1 receptors may help in understanding nociception, synaptic plasticity, and other physiological processes. ..
  13. Harris D, Eckhart A, Koch W. Galphaq and its Aktions. J Mol Cell Cardiol. 2006;40:589-92 pubmed
  14. McLaughlin J, Shen L, Holinstat M, Brooks J, Dibenedetto E, Hamm H. Functional selectivity of G protein signaling by agonist peptides and thrombin for the protease-activated receptor-1. J Biol Chem. 2005;280:25048-59 pubmed
    ..This model provides an estimate that peptide activation alters receptor/G protein binding to favor Galpha(q) activation over Galpha(12/13) by approximately 800-fold. ..
  15. Bastiani C, Gharib S, Simon M, Sternberg P. Caenorhabditis elegans Galphaq regulates egg-laying behavior via a PLCbeta-independent and serotonin-dependent signaling pathway and likely functions both in the nervous system and in muscle. Genetics. 2003;165:1805-22 pubmed
    ..Our data indicate that there are multiple signaling pathways downstream of EGL-30 and that different pathways could predominate with respect to the regulation of different behaviors. ..
  16. Bannister R, Melliti K, Adams B. Differential modulation of CaV2.3 Ca2+ channels by Galphaq/11-coupled muscarinic receptors. Mol Pharmacol. 2004;65:381-8 pubmed
  17. Bernstein L, Ramineni S, Hague C, Cladman W, Chidiac P, Levey A, et al. RGS2 binds directly and selectively to the M1 muscarinic acetylcholine receptor third intracellular loop to modulate Gq/11alpha signaling. J Biol Chem. 2004;279:21248-56 pubmed
  18. Takasaki J, Saito T, Taniguchi M, Kawasaki T, Moritani Y, Hayashi K, et al. A novel Galphaq/11-selective inhibitor. J Biol Chem. 2004;279:47438-45 pubmed
    ..This novel Galpha(q/11)-selective inhibitor is a promising and powerful tool for studying Galpha(q/11) protein activation, Galpha(q/11) -coupled receptor signaling, and Galpha(q/11)-mediated biological events. ..
  19. Mundell S, Pula G, McIlhinney R, Roberts P, Kelly E. Desensitization and internalization of metabotropic glutamate receptor 1a following activation of heterologous Gq/11-coupled receptors. Biochemistry. 2004;43:7541-51 pubmed
    ..Furthermore, the heterologous desensitization of mGluR1a is dependent upon the splice variant being in an active conformation. ..
  20. Chase D, Koelle M. Genetic analysis of RGS protein function in Caenorhabditis elegans. Methods Enzymol. 2004;389:305-20 pubmed
    ..elegans. This article describes general considerations regarding such experiments and provides detailed protocols for quantitatively measuring G-protein signaling phenotypes in C. elegans. ..
  21. Van Raamsdonk C, Fitch K, Fuchs H, de Angelis M, Barsh G. Effects of G-protein mutations on skin color. Nat Genet. 2004;36:961-8 pubmed
    ..Our results provide a mechanism that can explain several aspects of human pigmentary variation and show how polymorphism of essential proteins and signaling pathways can affect a single physiologic system. ..
  22. Cronin M, Diao F, Tsunoda S. Light-dependent subcellular translocation of Gqalpha in Drosophila photoreceptors is facilitated by the photoreceptor-specific myosin III NINAC. J Cell Sci. 2004;117:4797-806 pubmed
  23. Hartmann J, Blum R, Kovalchuk Y, Adelsberger H, Kuner R, Durand G, et al. Distinct roles of Galpha(q) and Galpha11 for Purkinje cell signaling and motor behavior. J Neurosci. 2004;24:5119-30 pubmed
    ..Our findings suggest an expression level-dependent action of Galpha(q) and Galpha11 for Purkinje cell signaling and assign specific roles of these two G(q) isoforms for motor coordination. ..
  24. Ueda H, Morishita R, Narumiya S, Kato K, Asano T. Galphaq/11 signaling induces apoptosis through two pathways involving reduction of Akt phosphorylation and activation of RhoA in HeLa cells. Exp Cell Res. 2004;298:207-17 pubmed
    ..These results demonstrate that Gq/11 signaling induces apoptosis by reducing insulin-stimulated Akt phosphorylation through tyrosine dephosphorylation and activating RhoA in HeLa cells. ..
  25. Molon B, Gri G, Bettella M, Gomez Mouton C, Lanzavecchia A, Martinez A C, et al. T cell costimulation by chemokine receptors. Nat Immunol. 2005;6:465-71 pubmed
  26. Barnes W, Reiter E, Violin J, Ren X, Milligan G, Lefkowitz R. beta-Arrestin 1 and Galphaq/11 coordinately activate RhoA and stress fiber formation following receptor stimulation. J Biol Chem. 2005;280:8041-50 pubmed
  27. Gamper N, Reznikov V, Yamada Y, Yang J, Shapiro M. Phosphatidylinositol [correction] 4,5-bisphosphate signals underlie receptor-specific Gq/11-mediated modulation of N-type Ca2+ channels. J Neurosci. 2004;24:10980-92 pubmed
    ..We suggest that differential use of PIP2 signals underlies specificity of Gq/11-coupled receptor actions on the channels ..
  28. Kong K, Billington C, Gandhi U, Panettieri R, Penn R. Cooperative mitogenic signaling by G protein-coupled receptors and growth factors is dependent on G(q/11). FASEB J. 2006;20:1558-60 pubmed
    ..Thus, G(q/11)-coupled receptors are the principal GPCR subfamily mediating cooperative mitogenic signaling in ASM, acting through Gbetagamma-dependent, and Src/arrestin-independent activation of PI3K and p70S6K. ..
  29. Faussner A, Wennerberg G, Schüssler S, Feierler J, Seidl C, Jochum M, et al. Alanine screening of the intracellular loops of the human bradykinin B receptor--effects on receptor maintenance, G protein activation and internalization. FEBS J. 2009;276:3491-503 pubmed publisher
    ..No conclusion could be drawn, however, with regard to the role of the DRY sequence, as the corresponding triplet mutation lacked binding capability. ..
  30. Lutz S, Shankaranarayanan A, Coco C, Ridilla M, Nance M, Vettel C, et al. Structure of Galphaq-p63RhoGEF-RhoA complex reveals a pathway for the activation of RhoA by GPCRs. Science. 2007;318:1923-7 pubmed
    ..We propose that this structure represents the crux of an ancient signal transduction pathway that is expected to be important in an array of physiological processes. ..
  31. Wainford R, Kurtz K, Kapusta D. Central G-alpha subunit protein-mediated control of cardiovascular function, urine output, and vasopressin secretion in conscious Sprague-Dawley rats. Am J Physiol Regul Integr Comp Physiol. 2008;295:R535-42 pubmed publisher
    ..These findings highlight the novel selective central Galpha-subunit protein-mediated control of cardiovascular vs. renal excretory function. ..
  32. Shi J, Zemaitaitis B, Muma N. Phosphorylation of Galpha11 protein contributes to agonist-induced desensitization of 5-HT2A receptor signaling. Mol Pharmacol. 2007;71:303-13 pubmed
    ..The phosphorylation of Galpha protein represents a novel mechanism involved in regulation of receptor signaling and agonist-induced desensitization of G protein-coupled receptors. ..
  33. Harris D, Cohn H, Pesant S, Zhou R, Eckhart A. Vascular smooth muscle G(q) signaling is involved in high blood pressure in both induced renal and genetic vascular smooth muscle-derived models of hypertension. Am J Physiol Heart Circ Physiol. 2007;293:H3072-9 pubmed
  34. Rudajev V, Novotny J, Hejnova L, Milligan G, Svoboda P. Dominant portion of thyrotropin-releasing hormone receptor is excluded from lipid domains. Detergent-resistant and detergent-sensitive pools of TRH receptor and Gqalpha/G11alpha protein. J Biochem. 2005;138:111-25 pubmed
    ..Trimeric G protein G(q)alpha/G(11)alpha occurs in both DRMs and in the bulk of plasma membranes, which is totally solubilized by TX-100. ..
  35. Tesmer V, Kawano T, Shankaranarayanan A, Kozasa T, Tesmer J. Snapshot of activated G proteins at the membrane: the Galphaq-GRK2-Gbetagamma complex. Science. 2005;310:1686-90 pubmed
    ..Galphaq forms an effector-like interaction with the GRK2 regulator of G protein signaling (RGS) homology domain that is distinct from and does not overlap with that used to bind RGS proteins such as RGS4. ..
  36. Scarselli M, Donaldson J. Constitutive internalization of G protein-coupled receptors and G proteins via clathrin-independent endocytosis. J Biol Chem. 2009;284:3577-85 pubmed publisher
    ..These findings demonstrate that GPCRs are versatile PM proteins that can utilize different mechanisms of internalization depending upon ligand activation. ..
  37. Ter Braak M, Danneberg K, Lichte K, Liphardt K, Ktistakis N, Pitson S, et al. Galpha(q)-mediated plasma membrane translocation of sphingosine kinase-1 and cross-activation of S1P receptors. Biochim Biophys Acta. 2009;1791:357-70 pubmed
    ..It is concluded that SphK1 is an important effector of Gq-coupled receptors, linking them via cross-activation of S1P receptors to G(i) and G12/13 signalling pathways. ..
  38. Marini P, Moriello A, Cristino L, Palmery M, De Petrocellis L, Di Marzo V. Cannabinoid CB1 receptor elevation of intracellular calcium in neuroblastoma SH-SY5Y cells: interactions with muscarinic and delta-opioid receptors. Biochim Biophys Acta. 2009;1793:1289-303 pubmed publisher
  39. Takimoto E, Koitabashi N, Hsu S, Ketner E, Zhang M, Nagayama T, et al. Regulator of G protein signaling 2 mediates cardiac compensation to pressure overload and antihypertrophic effects of PDE5 inhibition in mice. J Clin Invest. 2009;119:408-20 pubmed publisher
    ..Thus, RGS2 is required for early myocardial compensation to pressure overload and mediates the initial antihypertrophic and cardioprotective effects of PDE5 inhibitors. ..
  40. Abe K, Nakashima H, Ishida M, Miho N, Sawano M, Soe N, et al. Angiotensin II-induced osteopontin expression in vascular smooth muscle cells involves Gq/11, Ras, ERK, Src and Ets-1. Hypertens Res. 2008;31:987-98 pubmed publisher
    ..These signaling molecules may represent therapeutic targets for the prevention of pathological vascular remodeling. ..
  41. Toews J, Schram V, Weerth S, Mignery G, Russell J. Signaling proteins in the axoglial apparatus of sciatic nerve nodes of Ranvier. Glia. 2007;55:202-13 pubmed
  42. Go L, Mitchell J. Receptor-coupling properties of the invertebrate visual guanine nucleotide binding protein iGqalpha. Cell Signal. 2007;19:1919-27 pubmed
    ..Comparison of [(35)S]GTPgammaS binding rates helps explain the increased efficacy of the invertebrate G proteins. ..
  43. Jacamo R, Sinnett Smith J, Rey O, Waldron R, Rozengurt E. Sequential protein kinase C (PKC)-dependent and PKC-independent protein kinase D catalytic activation via Gq-coupled receptors: differential regulation of activation loop Ser(744) and Ser(748) phosphorylation. J Biol Chem. 2008;283:12877-87 pubmed publisher
    ..The present studies identify a novel mechanism induced by GPCR activation that leads to late, PKC-independent PKD activation. ..
  44. Ogata N, Kawaguchi H, Chung U, Roth S, Segre G. Continuous activation of G alpha q in osteoblasts results in osteopenia through impaired osteoblast differentiation. J Biol Chem. 2007;282:35757-64 pubmed
    ..We propose that continuous activation of the G alpha(q) signal in osteoblasts plays a crucial, previously unrecognized role in bone formation. ..
  45. Krishnaswamy N, Lacroix Pepin N, Chapdelaine P, Taniguchi H, Kauffenstein G, Chakravarti A, et al. Epidermal growth factor receptor is an obligatory intermediate for oxytocin-induced cyclooxygenase 2 expression and prostaglandin F2 alpha production in bovine endometrial epithelial cells. Endocrinology. 2010;151:1367-74 pubmed publisher
    ..Thus, EGFR may simultaneously activate c-Src and PI3K to amplify the OT signaling to increase the output of PGF(2 alpha) in bEEL cells. ..
  46. Xiao Z, Biancani P, Behar J. Effects of progesterone on motility and prostaglandin levels in the distal guinea pig colon. Am J Physiol Gastrointest Liver Physiol. 2009;297:G886-93 pubmed
    ..P4 also decreased the basal MI by increasing PGE(2) levels, and PGE(2) induced relaxation by upregulating Galpha(s) proteins. ..
  47. Uemura T, Kawasaki T, Taniguchi M, Moritani Y, Hayashi K, Saito T, et al. Biological properties of a specific Galpha q/11 inhibitor, YM-254890, on platelet functions and thrombus formation under high-shear stress. Br J Pharmacol. 2006;148:61-9 pubmed
    ..9 YM-254890 is a useful tool for investigating Galpha(q/11)-coupled receptor signaling and the physiological roles of Galpha(q/11). ..
  48. Clark M, Lambert N. Endogenous regulator of G-protein signaling proteins regulate the kinetics of Galphaq/11-mediated modulation of ion channels in central nervous system neurons. Mol Pharmacol. 2006;69:1280-7 pubmed
    ..These results suggest that endogenous RGS proteins regulate the kinetics of rapid Galphaq/11-mediated signals in central nervous system neurons by providing GAP activity. ..
  49. Peres C, Aronoff D, Serezani C, Flamand N, Faccioli L, Peters Golden M. Specific leukotriene receptors couple to distinct G proteins to effect stimulation of alveolar macrophage host defense functions. J Immunol. 2007;179:5454-61 pubmed
  50. Petrel C, Clauser E. Angiotensin II AT1 receptor constitutive activation: from molecular mechanisms to pathophysiology. Mol Cell Endocrinol. 2009;302:176-84 pubmed publisher
    ..Expression of such mutations in mice is linked to hypertension and cardiovascular diseases, but such natural mutations have not been identified in human pathology. ..
  51. Ni L, Guo P, Reddig K, Mitra M, Li H. Mutation of a TADR protein leads to rhodopsin and Gq-dependent retinal degeneration in Drosophila. J Neurosci. 2008;28:13478-87 pubmed publisher
    ..We propose that TADR-like proteins may also protect photoreceptors from degeneration in mammals including humans. ..
  52. McIntire W, MacCleery G, Murphree L, Kerchner K, Linden J, Garrison J. Influence of differential stability of G protein ?? dimers containing the ?11 subunit on functional activity at the M1 muscarinic receptor, A1 adenosine receptor, and phospholipase C-?. Biochemistry. 2006;45:11616-31 pubmed
    ..These results suggest that the stability of the beta4gamma11 dimer can modulate G protein activity at the receptor and effector. ..
  53. McElligott Z, Klug J, Nobis W, Patel S, Grueter B, Kash T, et al. Distinct forms of Gq-receptor-dependent plasticity of excitatory transmission in the BNST are differentially affected by stress. Proc Natl Acad Sci U S A. 2010;107:2271-6 pubmed publisher
    ..These data thus suggest that in the BNST, NE- and glutamate-activated G(q)-linked signaling pathways differentially tune glutamate synapse efficacy in response to stress. ..