Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi

Regulator of G-Protein Signaling 1 (RGS1)

  • Josephine Bou Dagher
  • Jae-Kyung LeeEmail author
Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_101824


Historical Background

G-protein-coupled receptors (GPCRs) are cell-surface transmembrane proteins that mediate the effects of a broad spectrum of biological signals. GPCRs signal through heterotrimeric G-proteins that are localized on the inner surface of the plasma membrane and that consist of three subunits: α, β, and γ subunits. Four families of Gα subunits can be distinguished based on their function and amino acid homology, and they are termed: Gαs, Gαi, Gαq, and Gα12 (Gilman 1987). Regulator of G-protein signaling (RGS) family proteins are important effectors that mediate the strength and duration of GPCR and act as negative regulators of the GPCR signaling pathways. RGS proteins function as GTPase-activating proteins (GAPs) that accelerate the GTPase activity of Gαsubunits, driving G-protein...

This is a preview of subscription content, log in to check access.


  1. Bouma G, Kaushiva A, Strober W. Experimental murine colitis is regulated by two genetic loci, including one on chromosome 11 that regulates IL-12 responses. Gastroenterology. 2002;123:554–65.PubMedPubMedCentralCrossRefGoogle Scholar
  2. Bowman EP, Campbell JJ, Druey KM, Scheschonka A, Kehrl JH, Butcher EC. Regulation of chemotactic and proadhesive responses to chemoattractant receptors by RGS (regulator of G-protein signaling) family members. J Biol Chem. 1998;273:28040–8.PubMedPubMedCentralCrossRefGoogle Scholar
  3. Caballero-Franco C, Kissler S. The autoimmunity-associated gene RGS1 affects the frequency of T follicular helper cells. Genes Immun. 2016;17:228–38. doi:10.1038/gene.2016.16.CrossRefPubMedPubMedCentralGoogle Scholar
  4. Cho H, Harrison K, Schwartz O, Kehrl JH. The aorta and heart differentially express RGS (regulators of G-protein signalling) proteins that selectively regulate sphingosine 1-phosphate, angiotensin II and endothelin-1 signalling. Biochem J. 2003;371:973–80. doi:10.1042/BJ20021769.CrossRefPubMedPubMedCentralGoogle Scholar
  5. Denecke, B, et al. RGS1 is expressed in monocytes and acts as a GTPase-activating protein for G-protein-coupled chemoattractant receptors. J Biol Chem. 1999;274(38):26860–26868.PubMedPubMedCentralCrossRefGoogle Scholar
  6. Druey KM, Blumer KJ, Kang VH, Kehrl JH. Inhibition of G-protein-mediated MAP kinase activation by a new mammalian gene family. Nature. 1996;379:742–6. doi:10.1038/379742a0.CrossRefPubMedPubMedCentralGoogle Scholar
  7. Gibbons DL, Abeler-Dorner L, Raine T, Hwang IY, Jandke A, Wencker M, et al. Cutting Edge: Regulator of G protein signaling-1 selectively regulates gut T cell trafficking and colitic potential. J Immunol. 2011;187:2067–71. doi:10.4049/jimmunol.1100833.CrossRefPubMedPubMedCentralGoogle Scholar
  8. Gilman AG. G proteins: transducers of receptor-generated signals. Annu Rev Biochem. 1987;56:615–49. doi:10.1146/annurev.bi.56.070187.003151.CrossRefPubMedPubMedCentralGoogle Scholar
  9. Grafstein-Dunn E, Young KH, Cockett MI, Khawaja XZ. Regional distribution of regulators of G-protein signaling (RGS) 1, 2, 13, 14, 16, and GAIP messenger ribonucleic acids by in situ hybridization in rat brain. Brain Res Mol Brain Res. 2001;88:113–23.PubMedPubMedCentralCrossRefGoogle Scholar
  10. Han SB, Moratz C, Huang NN, Kelsall B, Cho H, Shi CS, et al. Rgs1 and Gnai2 regulate the entrance of B lymphocytes into lymph nodes and B cell motility within lymph node follicles. Immunity. 2005;22:343–54. doi:10.1016/j.immuni.2005.01.017.CrossRefPubMedPubMedCentralGoogle Scholar
  11. Han JI, Huang NN, Kim DU, Kehrl JH. RGS1 and RGS13 mRNA silencing in a human B lymphoma line enhances responsiveness to chemoattractants and impairs desensitization. J Leukoc Biol. 2006;79:1357–68. doi:10.1189/jlb.1105693.CrossRefPubMedPubMedCentralGoogle Scholar
  12. Heximer SP, Cristillo AD, Forsdyke DR. Comparison of mRNA expression of two regulators of G-protein signaling, RGS1/BL34/1R20 and RGS2/G0S8, in cultured human blood mononuclear cells. DNA Cell Biol. 1997;16:589–98. doi:10.1089/dna.1997.16.589.CrossRefPubMedPubMedCentralGoogle Scholar
  13. Hong JX, Wilson GL, Fox CH, Kehrl JH. Isolation and characterization of a novel B cell activation gene. J Immunol. 1993;150:3895–904.PubMedPubMedCentralGoogle Scholar
  14. Hunt KA, Zhernakova A, Turner G, Heap GA, Franke L, Bruinenberg M, et al. Newly identified genetic risk variants for celiac disease related to the immune response. Nat Genet. 2008;40:395–402. doi:10.1038/ng.102.CrossRefPubMedPubMedCentralGoogle Scholar
  15. International Multiple Sclerosis Genetics C. IL12A, MPHOSPH9/CDK2AP1 and RGS1 are novel multiple sclerosis susceptibility loci. Genes Immun. 2010;11:397–405. doi:10.1038/gene.2010.28.CrossRefGoogle Scholar
  16. Johnson, BA, et al. Multiple sclerosis susceptibility alleles in African Americans. Genes Immun. 2010;11(4): 343–350.CrossRefGoogle Scholar
  17. Johnson BA, Wang J, Taylor EM, Caillier SJ, Herbert J, Khan OA, et al. Multiple sclerosis susceptibility alleles in African Americans. Genes Immun. 2010;11:343–50. doi:10.1038/gene.2009.81.CrossRefPubMedPubMedCentralGoogle Scholar
  18. Kardestuncer, T, et al. Cardiac myocytes express mRNA for ten RGS proteins: changes in RGS mRNA expression in ventricular myocytes and cultured atria. FEBS Lett. 1998;438(3):285–288.PubMedPubMedCentralCrossRefGoogle Scholar
  19. Kveberg L, Ryan JC, Rolstad B, Inngjerdingen M. Expression of regulator of G protein signalling proteins in natural killer cells, and their modulation by Ly49A and Ly49D. Immunology. 2005;115:358–65. doi:10.1111/j.1365-2567.2005.02174.x.CrossRefPubMedPubMedCentralGoogle Scholar
  20. Ladds G, Goddard A, Hill C, Thornton S, Davey J. Differential effects of RGS proteins on G alpha(q) and G alpha(11) activity. Cell Signal. 2007;19:103–13. doi:10.1016/j.cellsig.2006.05.027.CrossRefPubMedPubMedCentralGoogle Scholar
  21. Larminie C, Murdock P, Walhin JP, Duckworth M, Blumer KJ, Scheideler MA, et al. Selective expression of regulators of G-protein signaling (RGS) in the human central nervous system. Brain Res Mol Brain Res. 2004;122:24–34. doi:10.1016/j.molbrainres.2003.11.014.CrossRefPubMedPubMedCentralGoogle Scholar
  22. Lee JK, Bou Dagher J. Regulator of G-protein signaling (RGS)1 and RGS10 proteins as potential drug targets for neuroinflammatory and neurodegenerative diseases. AAPS J. 2016;18:545–9. doi:10.1208/s12248-016-9883-4.CrossRefPubMedPubMedCentralGoogle Scholar
  23. Moratz C, Kang VH, Druey KM, Shi CS, Scheschonka A, Murphy PM, et al. Regulator of G protein signaling 1 (RGS1) markedly impairs Gi alpha signaling responses of B lymphocytes. J Immunol. 2000;164:1829–38.PubMedPubMedCentralCrossRefGoogle Scholar
  24. Moratz C, Hayman JR, Gu H, Kehrl JH. Abnormal B-cell responses to chemokines, disturbed plasma cell localization, and distorted immune tissue architecture in Rgs1−/− mice. Mol Cell Biol. 2004;24:5767–75. doi:10.1128/MCB.24.13.5767-5775.2004.CrossRefPubMedPubMedCentralGoogle Scholar
  25. Mowry EM, Carey RF, Blasco MR, Pelletier J, Duquette P, Villoslada P, et al. Multiple sclerosis susceptibility genes: associations with relapse severity and recovery. PLoS One. 2013;8:e75416. doi:10.1371/journal.pone.0075416.CrossRefPubMedPubMedCentralGoogle Scholar
  26. Murphy JJ, Norton JD. Cell-type-specific early response gene expression during plasmacytoid differentiation of human B lymphocytic leukemia cells. Biochim Biophys Acta. 1990;1049:261–71.PubMedPubMedCentralCrossRefGoogle Scholar
  27. Newton JS, Deed RW, Mitchell EL, Murphy JJ, Norton JD. A B cell specific immediate early human gene is located on chromosome band 1q31 and encodes an alpha helical basic phosphoprotein. Biochim Biophys Acta. 1993;1216:314–6.PubMedPubMedCentralCrossRefGoogle Scholar
  28. Offermanns S, Simon MI. Organization of transmembrane signalling by heterotrimeric G proteins. Cancer Surv. 1996;27:177–98.PubMedPubMedCentralGoogle Scholar
  29. Panetta R, Guo Y, Magder S, Greenwood MT. Regulators of G-protein signaling (RGS) 1 and 16 are induced in response to bacterial lipopolysaccharide and stimulate c-fos promoter expression. Biochem Biophys Res Commun. 1999;259:550–6. doi:10.1006/bbrc.1999.0817.CrossRefPubMedPubMedCentralGoogle Scholar
  30. Patel J, McNeill E, Douglas G, Hale AB, de Bono J, Lee R, et al. RGS1 regulates myeloid cell accumulation in atherosclerosis and aortic aneurysm rupture through altered chemokine signalling. Nat Commun. 2015;6:6614. doi:10.1038/ncomms7614.CrossRefPubMedPubMedCentralGoogle Scholar
  31. Reif K, Cyster JG. RGS molecule expression in murine B lymphocytes and ability to down-regulate chemotaxis to lymphoid chemokines. J Immunol. 2000;164:4720–9.PubMedPubMedCentralCrossRefGoogle Scholar
  32. Riekenberg S, Farhat K, Debarry J, Heine H, Jung G, Wiesmuller KH, et al. Regulators of G-protein signalling are modulated by bacterial lipopeptides and lipopolysaccharide. FEBS J. 2009;276:649–59. doi:10.1111/j.1742-4658.2008.06813.x.CrossRefPubMedPubMedCentralGoogle Scholar
  33. 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. doi:10.1146/annurev.biochem.69.1.795.CrossRefPubMedPubMedCentralGoogle Scholar
  34. Sierra DA, Gilbert DJ, Householder D, Grishin NV, Yu K, Ukidwe P, et al. Evolution of the regulators of G-protein signaling multigene family in mouse and human. Genomics. 2002;79:177–85. doi:10.1006/geno.2002.6693.CrossRefPubMedPubMedCentralGoogle Scholar
  35. Smyth DJ, Plagnol V, Walker NM, Cooper JD, Downes K, Yang JH, et al. Shared and distinct genetic variants in type 1 diabetes and celiac disease. N Engl J Med. 2008;359:2767–77. doi:10.1056/NEJMoa0807917.CrossRefPubMedPubMedCentralGoogle Scholar
  36. Tran T, Paz P, Velichko S, Cifrese J, Belur P, Yamaguchi KD, et al. Interferonbeta-1b Induces the Expression of RGS1 a Negative Regulator of G-Protein Signaling. Int J Cell Biol. 2010;2010:529376. doi:10.1155/2010/529376.CrossRefPubMedPubMedCentralGoogle Scholar
  37. Watson N, Linder ME, Druey KM, Kehrl JH, Blumer KJ. RGS family members: GTPase-activating proteins for heterotrimeric G-protein alpha-subunits. Nature. 1996;383:172–5. doi:10.1038/383172a0.CrossRefPubMedPubMedCentralGoogle Scholar
  38. Xu X, Zeng W, Popov S, Berman DM, Davignon I, Yu K, et al. RGS proteins determine signaling specificity of Gq-coupled receptors. J Biol Chem. 1999;274:3549–56.PubMedPubMedCentralCrossRefGoogle Scholar
  39. Zheng B, De Vries L, Gist FM. Divergence of RGS proteins: evidence for the existence of six mammalian RGS subfamilies. Trends Biochem Sci. 1999;24:411–4.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Department of Physiology and Pharmacology, College of Veterinary MedicineUniversity of GeorgiaAthensUSA