Encyclopedia of Signaling Molecules

2012 Edition
| Editors: Sangdun Choi

Relaxin Family Peptide Receptors (RXFP) 3 and 4

  • Emma T. van der Westhuizen
  • Michelle L. Halls
  • Roger J. Summers
Reference work entry
DOI: https://doi.org/10.1007/978-1-4419-0461-4_583

Synonyms

Historical Background: Relaxin Family Peptides and Their Receptors

Relaxin family peptides including the relaxins 1–3, insulin-like peptides (INSL) 3–6, and insulin-like growth factors I and II have a similar architecture to insulin. These peptides are generally involved in the regulation of cell growth and metabolism. Relaxin was originally identified as a hormone important during pregnancy but is also now known to have roles in collagen remodeling, wound healing, cardiovascular responses, and as a brain neuropeptide. In the human, three independent genes produce three relaxin peptides, named relaxin-1, relaxin, and the recently discovered relaxin-3 (Bathgate et al. 2002). Relaxin-3 is primarily expressed in the brain as a neuropeptide that mediates stress and feeding responses in rats (Tanaka et al. 2005; McGowan et al. 2005, 2007). Relaxin-3 peptide sequences from different species are well conserved (Bathgate et al. 2002;...

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

References

  1. Bathgate RA, Samuel CS, Burazin TC, Layfield S, Claasz AA, Reytomas IG, et al. Human relaxin gene 3 (H3) and the equivalent mouse relaxin (M3) gene. Novel members of the relaxin peptide family. J Biol Chem. 2002;277(2):1148–57.PubMedCrossRefGoogle Scholar
  2. Boels K, Schaller HC. Identification and characterisation of GPR100 as a novel human G-protein-coupled bradykinin receptor. Br J Pharmacol. 2003;140:932–8.PubMedCrossRefGoogle Scholar
  3. Boels K, Hermans-Borgmeyer I, Schaller HC. Identification of a mouse ortholog of the G-protein-coupled receptor SALPR and its expression in adult mouse brain and during development. Brain Res Dev Brain Res. 2004;152:265–8.PubMedCrossRefGoogle Scholar
  4. Chen J, Kuei C, Sutton SW, Bonaventure P, Nepomuceno D, Eriste E, et al. Pharmacological characterization of relaxin-3/INSL7 receptors GPCR135 and GPCR142 from different mammalian species. J Pharmacol Exp Ther. 2005;312(1):83–95.PubMedCrossRefGoogle Scholar
  5. Conklin D, Lofton-Day CE, Haldeman BA, Ching A, Whitmore TE, Lok S, et al. Identification of INSL5, a new member of the insulin superfamily. Genomics. 1999;60(1):50–6.PubMedCrossRefGoogle Scholar
  6. Lein ES, Hawrylycz MJ, Ao N, Ayres M, Bensinger A, Bernard A, et al. Genome-wide atlas of gene expression in the adult mouse brain. Nature. 2007;445:168–76.PubMedCrossRefGoogle Scholar
  7. Liu C, Chen J, Sutton S, Roland B, Kuei C, Farmer N, et al. Identification of relaxin-3/INSL7 as a ligand for GPCR142. J Biol Chem. 2003a;278(50):50765–70.PubMedCrossRefGoogle Scholar
  8. Liu C, Eriste E, Sutton S, Chen J, Roland B, Kuei C, et al. Identification of relaxin-3/INSL7 as an endogenous ligand for the orphan G-protein-coupled receptor GPCR135. J Biol Chem. 2003b;278(50):50754–64.PubMedCrossRefGoogle Scholar
  9. Liu C, Chen J, Kuei C, Sutton S, Nepomucendo D, Bonaventure P, et al. Relaxin-3/insulin-like peptide 5 chimeric peptide, a selective ligand for G protein-coupled receptor (GPCR)135 and GPCR142 over leucine-rich repeat-containing G protein-coupled receptor 7. Mol Pharmacol. 2005;67:231–40.PubMedCrossRefGoogle Scholar
  10. Ma S, Bonaventure P, Ferraro T, Shen PJ, Burazin TC, Bathgate RA, et al. Relaxin-3 in GABA projection neurons of nucleus incertus suggests widespread influence on forebrain circuits via G-protein-coupled receptor-135 in the rat. Neuroscience. 2007;144:165–90.PubMedCrossRefGoogle Scholar
  11. Matsumoto M, Kamohara M, Sugimoto T, Hidaka K, Takasaki J, Saito T, et al. The novel G-protein coupled receptor SALPR shares sequence similarity with somatostatin and angiotensin receptors. Gene. 2000;248(1–2):183–9.PubMedCrossRefGoogle Scholar
  12. McGowan BM, Stanley SA, Smith KL, White NE, Connolly MM, Thompson EL, et al. Central relaxin-3 administration causes hyperphagia in male Wistar rats. Endocrinology. 2005;146(8):3295–300.PubMedCrossRefGoogle Scholar
  13. McGowan BM, Stanley SA, White NE, Spangeus A, Patterson M, Thompson EL, et al. Hypothalamic mapping of orexigenic action and Fos-like immunoreactivity following relaxin-3 administration in male Wistar rats. Am J Physiol. 2007;292(3):E913–9.Google Scholar
  14. Sutton SW, Bonaventure P, Kuei C, Roland B, Chen J, Nepomuceno D, et al. Distribution of G-protein-coupled receptor (GPCR)135 binding sites and receptor mRNA in the rat brain suggests a role for relaxin-3 in neuroendocrine and sensory processing. Neuroendocrinology. 2004;80(5):298–307.PubMedCrossRefGoogle Scholar
  15. Sutton SW, Bonaventure P, Kuei C, Nepomuceno D, Wu J, Zhu J, et al. G-protein-coupled receptor (GPCR)-142 does not contribute to relaxin-3 binding in the mouse brain: further support that relaxin-3 is the physiological ligand for GPCR135. Neuroendocrinology. 2005;82(3–4):139–50.PubMedCrossRefGoogle Scholar
  16. Tanaka M, Iijima N, Miyamoto Y, Fukusumi S, Itoh Y, Ozawa H, et al. Neurons expressing relaxin 3/INSL 7 in the nucleus incertus respond to stress. Eur J Neurosci. 2005;21:1659–70.PubMedCrossRefGoogle Scholar
  17. van der Westhuizen ET, Werry TD, Sexton PM, Summers RJ. The Relaxin Family Peptide Receptor 3 (RXFP3) activates ERK1/2 through a PKC dependent mechanism. Mol Pharmacol. 2007;71:1618–29.PubMedCrossRefGoogle Scholar
  18. van der Westhuizen ET, Christopoulos A, Sexton PM, Wade JD, Summers RJ. H2 Relaxin Is a Biased Ligand Relative to H3 Relaxin at the Relaxin Family Peptide Receptor 3 (RXFP3). Mol Pharmacol. 2010;77:759–72.PubMedCrossRefGoogle Scholar
  19. Wilkinson TN, Speed TP, Tregear GW, Bathgate RAD. Evolution of the relaxin-like peptide family. BMC Evol Biol. 2005;5(14):1471–2148.Google Scholar
  20. Zhu J, Kuei C, Sutton S, Kamme F, Yu J, Bonaventure P, et al. Identification of the domains in RXFP4 (GPCR142) responsible for the high affinity binding and agonistic activity of INSL5 at RXFP4 compared to RXFP3 (GPCR135). Eur J Pharmacol. 2008;590(1–3):43–52.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Emma T. van der Westhuizen
    • 1
  • Michelle L. Halls
    • 2
  • Roger J. Summers
    • 3
  1. 1.Institut de Recherche en Immunologie et CancérologieUniversité de MontréalMontréalCanada
  2. 2.Department of PharmacologyUniversity of CambridgeCambridgeUK
  3. 3.Drug Discovery BiologyMonash Institute of Pharmaceutical Sciences, Monash UniversityParkvilleAustralia