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Table of Contents
Vol. 17, No. 1, 2009
Issue release date: February 2009
Section title: Invited Review
Neurosignals 2009;17:42–54

Functions and Regulatory Mechanisms of Gq-Signaling Pathways

Mizuno N. · Itoh H.
Department of Cell Biology, Graduate School of Biological Sciences, Nara Institute of Science and Technology, Takayama, Ikoma, Nara, Japan
email Corresponding Author

Dr. H. Itoh

Department of Cell Biology, Graduate School of Biological Sciences

Nara Institute of Science and Technology

Takayama, Ikoma, Nara (Japan)

Tel. +81 743 72 5440, Fax +81 743 72 5449, E-Mail hitoh@bs.naist.jp


  1. Gilman AG: G proteins: transducers of receptor-generated signals. Annu Rev Biochem 1987;56:614–649.
    External Resources
  2. Kaziro Y, Itoh H, Kozasa T, Nakafuku M, Satoh T: Structure and function of signal-transducing GTP-binding proteins. Annu Rev Biochem 1991;60:349–400.
  3. Simon MI, Strathmann MP, Gautam N: Diversity of G proteins in signal transduction. Science 1991;252:802–808.
  4. Oldham WM, Hamm HE: Heterotrimeric G protein activation by G-protein-coupled receptors. Nat Rev Mol Cell Biol 2008;9:67–93.
    External Resources
  5. Rhee SG: Regulation of phosphoinositide-specific phospholipase C. Annu Rev Biochem 2001;70:281–312.
  6. Wu D, Katz A, Lee CH, Simon MI: Activation of phospholipase C by α1-adrenergic receptors is mediated by the α subunits of Gq family. J Biol Chem 1992;267:25798–25802.
  7. Smrcka AV, Sternweis PC: Regulation of purified subtypes of phosphatidylinositol-specific phospholipase C β by G protein α and β γ subunits. J Biol Chem 1993;268:9667–9674.
  8. Hepler JR, Kozasa T, Smrcka AV, Simon MI, Rhee SG, Sternweis PC, Gilman AG: Purification from Sf9 cells and characterization of recombinant Gqα and G11α. Activation of purified phospholipase C isozymes by Gα subunits. J Biol Chem 1993;268:14367–14375.
  9. Jiang H, Wu D, Simon MI: Activation of phospholipase C β4 by heterotrimeric GTP-binding proteins. J Biol Chem 1994;269:7593–7596.
  10. Kozasa T, Hepler JR, Smrcka AV, Simon MI, Rhee SG, Sternweis PC, Gilman AG: Purification and characterization of recombinant G16α from Sf9 cells: activation of purified phospholipase C isozymes by G-protein α subunits. Proc Natl Acad Sci USA 1993;90:9176–9180.
  11. Venkatakrishnan G, Exton JH: Identification of determinants in the α-subunit of Gq required for phospholipase C activation. J Biol Chem 1996;271:5066–5072.
  12. Park D, Jhon DY, Lee CW, Ryu SH, Rhee SG: Removal of the carboxyl-terminal region of phospholipase C-β1 by calpain abolishes activation by Gαq. J Biol Chem 1993;268:3710–3714.
  13. Kim CG, Park D, Rhee SG: The role of carboxyl-terminal basic amino acids in Gqα-dependent activation, particulate association, and nuclear localization of phospholipase C-β1. J Biol Chem 1996;271:21187–21192.
  14. Wang T, Pentyala S, Elliott JT, Dowal L, Gupta E, Rebecchi MJ, Scarlata S: Selective interaction of the C2 domains of phospholipase C-β1 and -β2 with activated Gαq subunits: an alternative function for C2-signaling modules. Proc Natl Acad Sci USA 1999;96:7843–7846.
  15. Biddlecome GH, Berstein G, Ross EM: Regulation of phospholipase C-β1 by Gq and m1 muscarinic cholinergic receptor. Steady-state balance of receptor-mediated activation and GTPase-activating protein-promoted deactivation. J Biol Chem 1996;271:7999–8007.
  16. Chidiac P, Ross EM: Phospholipase C-β1 directly accelerates GTP hydrolysis by Gαq and acceleration is inhibited by βγ subunits. J Biol Chem 1999;274:19639–19643.
  17. Paulssen RH, Woodson J, Liu Z, Ross EM: Carboxyl-terminal fragments of phospholipase C-β1 with intrinsic Gq GTPase-activating protein (GAP) activity. J Biol Chem 1996;271:26622–26629.
  18. Siderovski DP, Willard FS: The GAPs, GEFs, and GDIs of heterotrimeric G-protein α subunits. Int J Biol Sci 2005;1:51–66.
  19. Hollinger S, Hepler JR: Cellular regulation of RGS proteins: modulators and integrators of G protein signaling. Pharmacol Rev 2002;54:527–559.
  20. Huang C, Hepler JR, Gilman AG, Mumby SM: Attenuation of Gi- and Gq-mediated signaling by expression of RGS4 or GAIP in mammalian cells. Proc Natl Acad Sci USA 1997;94:6159–6163.
  21. Yan Y, Chi PP, Bourne HR: RGS4 inhibits Gq-mediated activation of mitogen-activated protein kinase and phosphoinositide synthesis. J Biol Chem 1997;272:11924–11927.
  22. Heximer SP, Watson N, Linder ME, Blumer KJ, Hepler JR: RGS2/G0S8 is a selective inhibitor of Gqα function. Proc Natl Acad Sci USA 1997;94:14389–14393.
  23. Neill JD, Duck LW, Sellers JC, Musgrove LC, Scheschonka A, Druey KM, Kehrl JH: Potential role for a regulator of G protein signaling (RGS3) in gonadotropin-releasing hormone-stimulated desensitization. Endocrinology 1997;138:843–846.
  24. Saitoh O, Murata Y, Odagiri M, Itoh M, Itoh H, Misaka T, Kubo Y: Alternative splicing of RGS8 gene determines inhibitory function of receptor type-specific Gq signaling. Proc Natl Acad Sci USA 2002;99:10138–10143.
  25. Beadling C, Druey, KM, Richter G, Kehrl JH, Smith KA: Regulators of G protein signaling exhibit distinct patterns of gene expression and target G protein specificity in human lymphocytes. J Immunol 1999;162:2677–2682.
  26. Zhou J, Moroi K, Nishiyama M, Usui H, Seki N, Ishida J, Fukamizu A, Kimura S: Characterization of RGS5 in regulation of G protein-coupled receptor signaling. Life Sci 2001;68:1457–1469.
  27. Park IK, Klug CA, Li K, Jerabek L, Li L, Nanamori M, Neubig RR, Hood L, Weissman IL, Clarke MF: Molecular cloning and characterization of a novel regulator of G-protein signaling from mouse hematopoietic stem cells. J Biol Chem 2001;276:915–923.
  28. Johnson EN, Druey KM: Functional characterization of the G protein regulator RGS13. J Biol Chem 2002;277:16768–16774.
  29. Druey KM, Blumer KJ, Kang VH, Kehrl JH: Inhibition of G-protein-mediated MAP kinase activation by a new mammalian gene family. Nature 1996;379:742–746.
  30. Chidiac P, Gadd ME, Hepler JR: Measuring RGS protein interactions with Gqα. Methods Enzymol 2002;344:686–702.
  31. Ingi T, Krumins AM Chidiac P, Brothers GM, Chung S, Snow BE, Barnes CA, Lanahan AA, Siderovski DP, Ross EM, Gilman AG, Worley PF: Dynamic regulation of RGS2 suggests a novel mechanism in G-protein signaling and neuronal plasticity. J Neurosci 1998;18:7178–7188.
  32. Hepler JR, Berman DM, Gilman AG, Kozasa T: RGS4 and GAIP are GTPase-activating proteins for Gqα and block activation of phospholipase Cβ by γ-thio-GTP-Gqα. Proc Natl Acad Sci USA 1997;94:428–432.
  33. Scheschonka A, Dessauer CW, Sinnarajah S, Chidiac P, Shi CS, Kehrl JH: RGS3 is a GTPase-activating protein for Giα and Gqα and a potent inhibitor of signaling by GTPase-deficient forms of Gqα and G11α. Mol Pharmacol 2000;58:719–728.
  34. Nagata Y, Oda M, Nakata H, Shozaki Y, Kozasa T, Todokoro K: A novel regulator of G-protein signaling bearing GAP activity for Gαi and Gαq in megakaryocytes. Blood 2001;97:3051–3060.
  35. Xu X, Zeng W, Popov S, Berman DM, Davignon I, Yu K, Yowe D, Offermanns S, Muallem S, Wilkie TM: RGS proteins determine signaling specificity of Gq-coupled receptors. J Biol Chem 1999;274:3549–3556.
  36. Jaffe AB, Hall A: Rho GTPases in transformation and metastasis. Adv Cancer Res 2002;84:57–80.
  37. Ridley AJ: Rho GTPases and actin dynamics in membrane protrusions and vesicle trafficking. Trends Cell Biol 2006;16:522–529.
  38. Rossman KL, Der CJ, Sondek J: GEF means go: turning on RHO GTPases with guanine nucleotide-exchange factors. Nat Rev Mol Cell Biol 2005;6:167–180.
  39. Schmidt A, Hall A: Guanine nucleotide exchange factors for Rho GTPases: turning on the switch. Genes Dev 2002;16:1587–1609.
  40. Kozasa T, Jiang X, Hart MJ, Sternweis PM, Singer WD, Gilman AG, Bollag G, Sternweis PC: p115 RhoGEF, a GTPase activating protein for Gα12 and Gα13. Science 1998;280:2109–2111.
  41. Hart MJ, Jiang X, Kozasa T, Roscoe W, Singer WD, Gilman AG, Sternweis PC, Bollag G: Direct stimulation of the guanine nucleotide exchange activity of p115 RhoGEF by Gα13. Science 1998;280:2112–2114.
  42. Fukuhara S, Murga C, Zohar M, Igishi T, Gutkind JS: A novel PDZ domain containing guanine nucleotide exchange factor links heterotrimeric G proteins to Rho. J Biol Chem 1999;274:5868–5879.
  43. Suzuki N, Nakamura S, Mano H, Kozasa T: Gα12 activates Rho GTPase through tyrosine-phosphorylated leukemia-associated RhoGEF. Proc Natl Acad Sci USA 2003;100:733–738.
  44. Lutz S, Freichel-Blomquist A, Yang Y, Rümenapp U, Jakobs KH, Schmidt M, Wieland T: The guanine nucleotide exchange factor p63RhoGEF, a specific link between Gq/11-coupled receptor signaling and RhoA. J Biol Chem 2005;280:11134–11139.
  45. Lutz S, Shankaranarayanan A, Coco C, Ridilla M, Nance MR, Vettel C, Baltus D, Evelyn CR, Neubig RR, Wieland T, Tesmer JJ: Structure of Gαq-p63RhoGEF-RhoA complex reveals a pathway for the activation of RhoA by GPCRs. Science 2007;318:1923–1927.
  46. 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;282:29201–29210.
  47. Williams SL, Lutz S, Charlie NK, Vettel C, Ailion M, Coco C, Tesmer JJ, Jorgensen EM, Wieland T, Miller KG: Trio’s Rho-specific GEF domain is the missing Gαq effector in C. elegans. Genes Dev 2007;21:2731–2746.
  48. Miller KG, Emerson MD, McManus JR, Rand JB: RIC-8 (Synembryn): a novel conserved protein that is required for Gqα signaling in the C. elegans nervous system. Neuron 2000;27:289–299.
  49. Miller KG, Rand JB: A role for RIC-8 (Synembryn) and GOA-1 (G(o)α) in regulating a subset of centrosome movements during early embryogenesis in Caenorhabditis elegans. Genetics 2000;156:1649–1660.
  50. Afshar K, Willard FS, Colombo K, Johnston CA, McCudden CR, Siderovski DP, Gönczy P: RIC-8 is required for GPR-1/2-dependent Gα function during asymmetric division of C. elegans embryos. Cell 2004;119:219–230.
  51. Couwenbergs C, Spilker AC, Gotta M: Control of embryonic spindle positioning and Gα activity by C. elegans RIC-8. Curr Biol 2004;14:1871–1876.
  52. David NB, Martin CA, Segalen M, Rosenfeld F, Schweisguth F, Bellaïche Y: Drosophila Ric-8 regulates Gαi cortical localization to promote Gαi-dependent planar orientation of the mitotic spindle during asymmetric cell division. Nat Cell Biol 2005;7:1083–1090.
  53. Hampoelz B, Hoeller O, Bowman SK, Dunican D, Knoblich JA: Drosophila Ric-8 is essential for plasma-membrane localization of heterotrimeric G proteins. Nat Cell Biol 2005;7:1099–1105.
  54. Wang H, Ng KH, Qian H, Siderovski DP, Chia W, Yu F: Ric-8 controls Drosophila neural progenitor asymmetric division by regulating heterotrimeric G proteins. Nat Cell Biol 2005;7:1091–1098.
  55. Tall GG, Krumins AM, Gilman AG: Mammalian Ric-8A (synembryn) is a heterotrimeric Gα protein guanine nucleotide exchange factor. J Biol Chem 2003;278:8356–8362.
  56. Tõnissoo T, Meier R, Talts K, Plaas M, Karis A: Expression of ric-8 (synembryn) gene in the nervous system of developing and adult mouse. Gene Expr Patterns 2003;3:591–594.
  57. Nishimura A, Okamoto M, Sugawara Y, Mizuno N, Yamauchi J, Itoh H: Ric-8A potentiates Gq-mediated signal transduction by acting downstream of G protein-coupled receptor in intact cells. Genes Cells 2006;11:487–498.
  58. Von Dannecker LE, Mercadante AF, Malnic B: Ric-8B, an olfactory putative GTP exchange factor, amplifies signal transduction through the olfactory-specific G-protein Gαolf. J Neurosci 2005;25:3793–3800.
  59. Von Dannecker LE, Mercadante AF, Malnic B: Ric-8B promotes functional expression of odorant receptors. Proc Natl Acad Sci USA 2006;103:9310–9314.
  60. Brown DA, London E: Structure and function of sphingolipid- and cholesterol-rich membrane rafts. J Biol Chem 2000;275:17221–17224.
  61. Oh P, Schnitzer JE: Segregation of heterotrimeric G proteins in cell surface microdomains. Gq binds caveolin to concentrate in caveolae, whereas Gi and Gs target lipid rafts by default. Mol Biol Cell 2001;12:685–698.
  62. Gonzalez E, Nagiel A, Lin AJ, Golan DE, Michel T: Small interfering RNA-mediated down-regulation of caveolin-1 differentially modulates signaling pathways in endothelial cells. J Biol Chem 2004;279:40659–40669.
  63. Bhatnagar A, Sheffler DJ, Kroeze WK, Compton-Toth B, Roth BL: Caveolin-1 interacts with 5-HT2A serotonin receptors and profoundly modulates the signaling of selected Gαq-coupled protein receptors. J Biol Chem 2004;279:34614–34623.
  64. Sugawara Y, Nishii H, Takahashi T, Yamauchi J, Mizuno N, Tago K, Itoh H: The lipid raft proteins flotillins/reggies interact with Gαq and are involved in Gq-mediated p38 mitogen-activated protein kinase activation through tyrosine kinase. Cell Signal 2007;19:1301–1308.
  65. Schulte T, Paschke KA, Laessing U, Lottspeich F, Stuermer CA: Reggie-1 and reggie-2, two cell surface proteins expressed by retinal ganglion cells during axon regeneration. Development 1997;124:577–587.
  66. Bickel PE, Scherer PE, Schnitzer JE, Oh P, Lisanti MP, Lodish HF: Flotillin and epidermal surface antigen define a new family of caveolae-associated integral membrane proteins. J Biol Chem 1997;272:13793–13802.
  67. Tavernarakis N, Driscoll M, Kyrpides NC: The SPFH domain: implicated in regulating targeted protein turnover in stomatins and other membrane-associated proteins. Trends Biochem Sci 1999;24:425–427.
  68. Browman DT, Hoegg MB, Robbins SM: The SPFH domain-containing proteins: more than lipid raft markers. Trends Cell Biol 2007;17:394–402.
  69. Yamauchi J, Nagao M, Kaziro Y, Itoh H: Activation of p38 mitogen-activated protein kinase by signaling through G protein-coupled receptors. Involvement of Gβγ and Gαq/11 subunits. J Biol Chem 1997;272:27771–27777.
  70. Nagao M, Yamauchi J, Kaziro Y, Itoh H: Involvement of protein kinase C and Src family tyrosine kinase in Gαq/11-induced activation of c-Jun N-terminal kinase and p38 mitogen-activated protein kinase. J Biol Chem 1998;273:22892–22898.
  71. Moss J, Vaughan M: Activation of adenylate cyclase by choleragen. Annu Rev Biochem 1979;48:581–600.
  72. Van Dop C, Tsubokawa M, Bourne HR, Ramachandran J: Amino acid sequence of retinal transducin at the site ADP-ribosylated by cholera toxin. J Biol Chem 1984;259:696–698.
  73. Katada T, Ui M: Direct modification of the membrane adenylate cyclase system by islet-activating protein due to ADP-ribosylation of a membrane protein. Proc Natl Acad Sci USA 1982;79:3129–3133.
  74. Kurose H, Katada T, Amano T, Ui M: Specific uncoupling by islet-activating protein, pertussis toxin, of negative signal transduction via α-adrenergic, cholinergic, and opiate receptors in neuroblastoma × glioma hybrid cells. J Biol Chem 1983;258:4870–4875.
  75. Fields TA, Casey PJ: Signalling functions and biochemical properties of pertussis toxin-resistant G-proteins. Biochem J 1997;321:561–571.
  76. Foged NT: Pasteurella multocida toxin. The characterisation of the toxin and its significance in the diagnosis and prevention of progressive atrophic rhinitis in pigs. APMIS 1992;25(suppl):1–56.
  77. Harmey D, Stenbeck G, Nobes CD, Lax AJ, Grigoriadis AE: Regulation of osteoblast differentiation by Pasteurella multocida toxin (PMT): a role for Rho GTPase in bone formation. J Bone Miner Res 2004;19:661–670.
  78. Lax AJ, Pullinger GD, Baldwin MR, Harmey D, Grigoriadis AE, Lakey JH: The Pasteurella multocida toxin interacts with signalling pathways to perturb cell growth and differentiation. Int J Med Microbiol 2004;293:505–512.
  79. Staddon JM, Barker CJ, Murphy AC, Chanter N, Lax AJ, Michell RH, Rozengurt E: Pasteurella multocida toxin, a potent mitogen, increases inositol 1,4,5-trisphosphate and mobilizes Ca2+ in Swiss 3T3 cells. J Biol Chem 1991;266:4840–4847.
  80. Wilson BA, Zhu X, Ho M, Lu L: Pasteurella multocida toxin activates the inositol triphosphate signaling pathway in Xenopus oocytes via Gqα-coupled phospholipase C-β1. J Biol Chem 1997;272:1268–1275.
  81. Murphy AC, Rozengurt E: Pasteurella multocida toxin selectively facilitates phosphatidylinositol 4,5-bisphosphate hydrolysis by bombesin, vasopressin, and endothelin. Requirement for a functional G protein. J Biol Chem 1992;267:25296–25303.
  82. Wilson BA, Ho M: Pasteurella multocida toxin as a tool for studying Gq signal transduction. Rev Physiol Biochem Pharmacol 2004;152:93–109.
  83. Zywietz A, Gohla A, Schmelz M, Schultz G, Offermanns S: Pleiotropic effects of Pasteurella multocida toxin are mediated by Gq-dependent and -independent mechanisms. Involvement of Gq but not G11. J Biol Chem 2001;276:3840–3845.
  84. Orth JH, Lang S, Aktories K: Action of Pasteurella multocida toxin depends on the helical domain of Gαq. J Biol Chem 2004;279:34150–34155.
  85. Essler M, Hermann K, Amano M, Kaibuchi K, Heesemann J, Weber PC, Aepfelbacher M: Pasteurella multocida toxin increases endothelial permeability via Rho kinase and myosin light chain phosphatase. J Immunol 1998;161:5640–5646.
  86. Seo B, Choy EW, Maudsley S, Miller WE, Wilson BA, Luttrell LM: Pasteurella multocida toxin stimulates mitogen-activated protein kinase via Gq/11-dependent transactivation of the epidermal growth factor receptor. J Biol Chem 2000;275:2239–2245.
  87. Lacerda HM, Lax AJ, Rozengurt E: Pasteurella multocida toxin, a potent intracellularly acting mitogen, induces p125FAK and paxillin tyrosine phosphorylation, actin stress fiber formation, and focal contact assembly in Swiss 3T3 cells. J Biol Chem 1996;271:439–445.
  88. Vogt S, Grosse R, Schultz G, Offermanns S: Receptor-dependent RhoA activation in G12/G13-deficient cells: genetic evidence for an involvement of Gq/G11. J Biol Chem 2003;278:28743–28749.
  89. Booden MA, Siderovski DP, Der CJ: Leukemia-associated Rho guanine nucleotide exchange factor promotes Gαq-coupled activation of RhoA. Mol Cell Biol 2002;22:4053–4061.
  90. Sagi SA, Seasholtz TM, Kobiashvili M, Wilson BA, Toksoz D, Brown JH: Physical and functional interactions of Gαq with Rho and its exchange factors. J Biol Chem 2001;276:15445–15452.
  91. Orth JH, Lang S, Taniguchi M, Aktories K: Pasteurella multocida toxin-induced activation of RhoA is mediated via two families of Gα proteins, Gαq and Gα12/13. J Biol Chem 2005;280:36701–36707.
  92. Pettit RK, Ackermann MR, Rimler RB: Receptor-mediated binding of Pasteurella multocida dermonecrotic toxin to canine osteosarcoma and monkey kidney (vero) cells. Lab Invest 1993;69:94–100.
  93. Kitadokoro K, Kamitani S, Miyazawa M, Hanajima-Ozawa M, Fukui A, Miyake M, Horiguchi Y: Crystal structures reveal a thiol protease-like catalytic triad in the C-terminal region of Pasteurella multocida toxin. Proc Natl Acad Sci USA 2007;104:5139–5144.
  94. Aminova LR, Luo S, Bannai Y, Ho M, Wilson BA: The C3 domain of Pasteurella multocida toxin is the minimal domain responsible for activation of Gq-dependent calcium and mitogenic signaling. Protein Sci 2008;17:945–949.
  95. Baldwin MR, Pullinger GD, Lax AJ: Pasteurella multocida toxin facilitates inositol phosphate formation by bombesin through tyrosine phosphorylation of Gαq. J Biol Chem 2003;278:32719–32725.
  96. Orth JH, Lang S, Preuss I, Milligan G, Aktories K: Action of Pasteurella multocida toxin on Gαq is persistent and independent of interaction with G-protein-coupled receptors. Cell Signal 2007;19:2174–2182.
  97. Taniguchi M, Nagai K, Arao N, Kawasaki T, Saito T, Moritani Y, Takasaki J, Hayashi K, Fujita S, Suzuki K, Tsukamoto S: YM-254890, a novel platelet aggregation inhibitor produced by Chromobacterium sp. QS3666. J Antibiot (Tokyo) 2003;56:358–363.
  98. Taniguchi M, Suzumura K, Nagai K, Kawasaki T, Takasaki J, Sekiguchi M, Moritani Y, Saito T, Hayashi K, Fujita S, Tsukamoto S, Suzuki K: YM-254890 analogues, novel cyclic depsipeptides with Gαq/11 inhibitory activity from Chromobacterium sp. QS3666. Bioorg Med Chem 2004;12:3125–3133.
  99. Kawasaki T, Taniguchi M, Moritani Y, Hayashi K, Saito T, Takasaki J, Nagai K, Inagaki O, Shikama H: Antithrombotic and thrombolytic efficacy of YM-254890, a G q/11 inhibitor, in a rat model of arterial thrombosis. Thromb Haemost 2003;90:406–413.
  100. Uemura T, Takamatsu H, Kawasaki T, Taniguchi M, Yamamoto E, Tomura Y, Uchida W, Miyata K: Effect of YM-254890, a specific Gαq/11 inhibitor, on experimental peripheral arterial disease in rats. Eur J Pharmacol 2006;536:154–161.
  101. Uemura T, Kawasaki T, Taniguchi M, Moritani Y, Hayashi K, Saito T, Takasaki J, Uchida W, Miyata K: Biological properties of a specific Gαq/11 inhibitor, YM-254890, on platelet functions and thrombus formation under high-shear stress. Br J Pharmacol 2006;148:61–69.
  102. Takasaki J, Saito T, Taniguchi M, Kawasaki T, Moritani Y, Hayashi K, Kobori M: A novel Gαq/11-selective inhibitor. J Biol Chem 2004;279:47438–47445.
  103. Matsuo A, Matsumoto S, Nagano M, Masumoto KH, Takasaki J, Matsumoto M, Kobori M, Katoh M, Shigeyoshi Y: Molecular cloning and characterization of a novel Gq-coupled orphan receptor GPRg1 exclusively expressed in the central nervous system. Biochem Biophys Res Commun 2005;331:363–369.
  104. Morishita R, Ueda H, Ito H, Takasaki J, Nagata K, Asano T: Involvement of Gq/11 in both integrin signal-dependent and -independent pathways regulating endothelin-induced neural progenitor proliferation. Neurosci Res 2007;59:205–214.
  105. Veale EL, Kennard LE, Sutton GL, MacKenzie G, Sandu C, Mathie A: Gαq-mediated regulation of TASK3 two-pore domain potassium channels: the role of protein kinase C. Mol Pharmacol 2007;71:1666–1675.
  106. Offermanns S, Toombs CF, Hu YH, Simon MI: Defective platelet activation in Gαq-deficient mice. Nature 1997;389:183–186.
  107. Offermanns S, Hashimoto K, Watanabe M, Sun W, Kurihara H, Thompson RF, Inoue Y, Kano M, Simon MI: Impaired motor coordination and persistent multiple climbing fiber innervation of cerebellar Purkinje cells in mice lacking Gαq. Proc Natl Acad Sci USA 1997;94:14089–14094.
  108. Offermanns S, Zhao LP, Gohla A, Sarosi I, Simon MI, Wilkie TM: Embryonic cardiomyocyte hypoplasia and craniofacial defects in Gαq/Gα11-mutant mice. EMBO J 1998;17:4304–4312.
  109. Davignon I, Catalina MD, Smith D, Montgomery J, Swantek J, Croy J, Siegelman M, Wilkie TM: Normal hematopoiesis and inflammatory responses despite discrete signaling defects in Gα15 knockout mice. Mol Cell Biol 2000;20:797–804.
  110. Wettschureck N, Moers A, Offermanns S: Mouse models to study G-protein-mediated signaling. Pharmacol Ther 2004;101:75–89.
  111. Ivey K, Tyson B, Ukidwe P, McFadden DG, Levi G, Olson EN, Srivastava D, Wilkie TM: Gαq and Gα11 proteins mediate endothelin-1 signaling in neural crest-derived pharyngeal arch mesenchyme. Dev Biol 2003;255:230–237.
  112. Wettschureck N, Moers A, Wallenwein B, Parlow AF, Maser-Gluth C, Offermanns S: Loss of Gq/11 family G proteins in the nervous system causes pituitary somatotroph hypoplasia and dwarfism in mice. Mol Cell Biol 2005;25:1942–1948.
  113. Shioda S, Ohtaki H, Nakamachi T, Dohi K, Watanabe J, Nakajo S, Arata S, Kitamura S, Okuda H, Takenoya F, Kitamura Y: Pleiotropic functions of PACAP in the central nervous system: neuroprotection and neurodevelopment. Ann NY Acad Sci 2006;1070:550–560.
  114. Ohno F, Watanabe J, Sekihara H, Hirabayashi T, Arata S, Kikuyama S, Shioda S, Nakaya K, Nakajo S: Pituitary adenylate cyclase-activating polypeptide promotes differentiation of mouse neural stem cells into astrocytes. Regul Pept 2005;126:115–122.
  115. Nishimoto M, Furuta A, Aoki S, Kudo Y, Miyakawa H, Wada K: PACAP/PAC1 autocrine system promotes proliferation and astrogenesis in neural progenitor cells. Glia 2007;55:317–327.
  116. Masaki T: Historical review: endothelin. Trends Pharmacol Sci 2004;25:219–224.
  117. Shin MK, Levorse JM, Ingram RS, Tilghman SM: The temporal requirement for endothelin receptor-B signalling during neural crest development. Nature 1999;402:496–501.
  118. Shinohara H, Udagawa J, Morishita R, Ueda H, Otani H, Semba R, Kato K, Asano T: Gi2 signaling enhances proliferation of neural progenitor cells in the developing brain. J Biol Chem 2004;279:41141–41148.
  119. Hatten ME: New directions in neuronal migration. Science 2002;297:1660–1663.
  120. Behar TN, Schaffner AE, Scott CA, Greene CL, Barker JL: GABA receptor antagonists modulate postmitotic cell migration in slice cultures of embryonic rat cortex. Cereb Cortex 2000;10:899–909.
  121. Behar TN, Smith SV, Kennedy RT, McKenzie JM, Maric I, Barker JL: GABAB receptors mediate motility signals for migrating embryonic cortical cells. Cereb Cortex 2001;11:744–753.
  122. Stumm RK, Zhou C, Ara T, Lazarini F, Dubois-Dalcq M, Nagasawa T, Höllt V, Schulz S: CXCR4 regulates interneuron migration in the developing neocortex. J Neurosci 2003;23:5123–5130.
  123. Mizuno N, Kokubu,H, Sato M, Nishimura A, Yamauchi J, KuroseH, Itoh H: G protein-coupled receptor signaling through Gq and JNK negatively regulates neural progenitor cell migration. Proc Natl Acad Sci USA 2005;102:12365–12370.
  124. Tabata H, Nakajima K: Multipolar migration: the third mode of radial neuronal migration in the developing cerebral cortex. J Neurosci 2003;23:9996–10001.
  125. Nadarajah B, Parnavelas JG: Modes of neuronal migration in the developing cerebral cortex. Nat Rev Neurosci 2002;3:423–432.
  126. Piao X, Hill RS, Bodell A, Chang BS, Basel-Vanagaite L, Straussberg R, Dobyns WB, Qasrawi B, Winter RM, Innes AM, Voit T, Ross ME, Michaud JL, Déscarie JC, Barkovich AJ, Walsh CA: G protein-coupled receptor-dependent development of human frontal cortex. Science 2004;303:2033–2036.
  127. Little KD, Hemler ME, Stipp CS: Dynamic regulation of a GPCR-tetraspanin-G protein complex on intact cells: central role of CD81 in facilitating GPR56-Gαq/11 association. Mol Biol Cell 2004;15:2375–2387.
  128. Iguchi T, Sakata K, Yoshizaki K, Tago K, Mizuno N, Itoh H: Orphan G protein-coupled receptor GPR56 regulates neural progenitor cell migration via a Gα12/13 and Rho pathway. J Biol Chem 2008;283:14469–14478.
  129. Orth JH, Fester I, Preuss I, Agnoletto L, Wilson BA, Aktories K: Activation of Gαi and subsequent uncoupling of receptor-Gαi signaling by Pasteurella multocida toxin. J Biol Chem 2008;283:23288–23294.