Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi

Regulator of G Protein Signaling 5 (RGS5)

  • Zhi-Jie Li
  • Ruth GanssEmail author
Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_101794


Historical Background

Regulator of G protein signaling (RGS) molecules comprise a large family of proteins (>35 in mammals) which modulate signaling downstream of G protein-coupled receptors (GPCRs). All family members share an evolutionary conserved RGS domain which confers guanosine triphosphatase (GTPase) activity (GAP) for the heterotrimeric G protein alpha subunit (Gα). Upon GPCR activation and Gα dissociation, RGS molecules facilitate GTP hydrolysis by the Gα subunit and thus accelerate reassociation of heterotrimeric G proteins with their receptors and termination of GPCR signaling. RGS molecules are therefore negative regulators of GPCR signaling (Fig. 1). RGS5 belongs to the B/R4 subfamily of RGS molecules and – like other B/R4 proteins such as RGS1, 2, 3, 4, 8, 13, 16, 18, and 21 – is a small protein with little more than a 120 aa RGS domain and 33 aa N-terminal part which is important for membrane association (Fig. 2a) (Ganss 2015...
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  1. Adams LD, Geary RL, McManus B, Schwartz SM. A comparison of aorta and vena cava medial message expression by cDNA array analysis identifies a set of 68 consistently differentially expressed genes, all in aortic media. Circ Res. 2000;87:623–31.PubMedPubMedCentralCrossRefGoogle Scholar
  2. Arnold C, Feldner A, Pfisterer L, Hodebeck M, Troidl K, Genove G, et al. RGS5 promotes arterial growth during arteriogenesis. EMBO Mol Med. 2014;6:1075–89.PubMedPubMedCentralCrossRefGoogle Scholar
  3. Bahrami AJ, Gunaje JJ, Hayes BJ, Riehle KJ, Kenerson HL, Yeung RS, et al. Regulator of g-protein signaling-5 is a marker of hepatic stellate cells and expression mediates response to liver injury. PLoS One. 2014;9:e108505.PubMedPubMedCentralCrossRefGoogle Scholar
  4. Berger M, Bergers G, Arnold B, Hammerling GJ, Ganss R. Regulator of G-protein signaling-5 induction in pericytes coincides with active vessel remodeling during neovascularization. Blood. 2005;105:1094–101.PubMedPubMedCentralCrossRefGoogle Scholar
  5. Bondjers C, Kalen M, Hellstrom M, Scheidl SJ, Abramsson A, Renner O, et al. Transcription profiling of platelet-derived growth factor-B-deficient mouse embryos identifies RGS5 as a novel marker for pericytes and vascular smooth muscle cells. Am J Pathol. 2003;162:721–9.PubMedPubMedCentralCrossRefGoogle Scholar
  6. Cheng WL, Wang PX, Wang T, Zhang Y, Du C, Li H, et al. Regulator of G-protein signalling 5 protects against atherosclerosis in apolipoprotein E-deficient mice. Br J Pharmacol. 2015;172:5676–89.PubMedPubMedCentralCrossRefGoogle Scholar
  7. Cho H, Kozasa T, Bondjers C, Betsholtz C, Kehrl JH. Pericyte-specific expression of Rgs5: implications for PDGF and EDG receptor signaling during vascular maturation. FASEB J. 2003;17:440–2.PubMedPubMedCentralCrossRefGoogle Scholar
  8. Daniel JM, Prock A, Dutzmann J, Sonnenschein K, Thum T, Bauersachs J, et al. Regulator of G-protein signaling 5 prevents smooth muscle cell proliferation and attenuates Neointima formation. Arterioscler Thromb Vasc Biol. 2016;36:317–2.PubMedPubMedCentralCrossRefGoogle Scholar
  9. Deng W, Wang X, Xiao J, Chen K, Zhou H, Shen D, et al. Loss of regulator of G protein signaling 5 exacerbates obesity, hepatic steatosis, inflammation and insulin resistance. PLoS One. 2012;7:e30256.PubMedPubMedCentralCrossRefGoogle Scholar
  10. Ganss R. Keeping the balance right: regulator of G protein signaling 5 in vascular physiology and pathology. Prog Mol Biol Transl Sci. 2015;133:93–121.PubMedPubMedCentralCrossRefGoogle Scholar
  11. Hamzah J, Jugold M, Kiessling F, Rigby P, Manzur M, Marti HH, et al. Vascular normalization in Rgs5-deficient tumours promotes immune destruction. Nature. 2008;453:410–4.PubMedPubMedCentralCrossRefGoogle Scholar
  12. Holobotovskyy V, Manzur M, Tare M, Burchell J, Bolitho E, Viola H, et al. Regulator of G-protein signaling 5 controls blood pressure homeostasis and vessel wall remodeling. Circ Res. 2013;112:781–91.PubMedPubMedCentralCrossRefGoogle Scholar
  13. Holobotovskyy V, Chong YS, Burchell J, He B, Phillips M, Leader L, et al. Regulator of G protein signaling 5 is a determinant of gestational hypertension and preeclampsia. Sci Transl Med. 2015;7:290ra88.PubMedPubMedCentralCrossRefGoogle Scholar
  14. Hu M, Chen X, Zhang J, Wang D, Fang X, Wang X, et al. Over-expression of regulator of G protein signaling 5 promotes tumor metastasis by inducing epithelial-mesenchymal transition in hepatocellular carcinoma cells. J Surg Oncol. 2013;108:192–6.PubMedPubMedCentralCrossRefGoogle Scholar
  15. Labuda M, Laberge S, Briere J, Berube D, Krajinovic M. RGS5 gene and therapeutic response to short acting bronchodilators in paediatric asthma patients. Pediatr Pulmonol. 2013;48:970–5.PubMedPubMedCentralCrossRefGoogle Scholar
  16. Lee MJ, Tasaki T, Moroi K, An JY, Kimura S, Davydov IV, et al. RGS4 and RGS5 are in vivo substrates of the N-end rule pathway. Proc Natl Acad Sci U S A. 2005;102:15030–5.PubMedPubMedCentralCrossRefGoogle Scholar
  17. Li H, He C, Feng J, Zhang Y, Tang Q, Bian Z, et al. Regulator of G protein signaling 5 protects against cardiac hypertrophy and fibrosis during biomechanical stress of pressure overload. Proc Natl Acad Sci U S A. 2010;107:13818–23.PubMedPubMedCentralCrossRefGoogle Scholar
  18. Mahoney Jr WM, Gunaje J, Daum G, Dong XR, Majesky MW. Regulator of G-protein signaling – 5 (RGS5) is a novel repressor of hedgehog signaling. PLoS One. 2013;8:e61421.PubMedPubMedCentralCrossRefGoogle Scholar
  19. Qin M, Liu X, Liu T, Wang T, Huang C. Potential Role of Regulator of G-Protein Signaling 5 in the Protection of Vagal-Related Bradycardia and Atrial Tachyarrhythmia. J Am Heart Assoc. 2016;5:e002783.PubMedPubMedCentralGoogle Scholar
  20. Seki N, Hattori A, Sugano S, Suzuki Y, Nakagawara A, Ohhira M, et al. Isolation, tissue expression, and chromosomal assignment of a novel human gene which encodes a protein with RING finger motif. J Hum Genet. 1998;43:272–4.PubMedPubMedCentralCrossRefGoogle Scholar
  21. Silini A, Ghilardi C, Figini S, Sangalli F, Fruscio R, Dahse R, et al. Regulator of G-protein signaling 5 (RGS5) protein: a novel marker of cancer vasculature elicited and sustained by the tumor’s proangiogenic microenvironment. Cell Mol Life Sci. 2012;69:1167–78.PubMedPubMedCentralCrossRefGoogle Scholar
  22. Volz NB, Stintzing S, Zhang W, Yang D, Ning Y, Wakatsuki T, et al. Genes involved in pericyte-driven tumor maturation predict treatment benefit of first-line FOLFIRI plus bevacizumab in patients with metastatic colorectal cancer. Pharm J. 2015;15:69–76.Google Scholar
  23. Wang Z, Huang H, He W, Kong B, Hu H, Fan Y, et al. Regulator of G-protein signaling 5 protects cardiomyocytes against apoptosis during in vitro cardiac ischemia-reperfusion in mice by inhibiting both JNK1/2 and P38 signaling pathways. Biochem Biophys Res Commun. 2016;473:551–7.PubMedPubMedCentralCrossRefGoogle Scholar
  24. Yang Z, Cooper PR, Damera G, Mukhopadhyay I, Cho H, Kehrl JH, et al. Beta-agonist-associated reduction in RGS5 expression promotes airway smooth muscle hyper-responsiveness. J Biol Chem. 2011;286:11444–55.PubMedPubMedCentralCrossRefGoogle Scholar
  25. Zhang H, Gu S, Al-Sabeq B, Wang S, He J, Tam A, et al. Origin-specific epigenetic program correlates with vascular bed-specific differences in Rgs5 expression. FASEB J. 2012;26:181–91.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.The Harry Perkins Institute of Medical ResearchThe University of Western Australia Centre for Medical ResearchNedlandsAustralia