Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi

Relaxin Family Peptide Receptors RXFP3 and RXFP4

  • Martina Kocan
  • Sheng Yu Ang
  • Roger J. Summers
Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_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. In the human, three independent genes produce three relaxin peptides, named relaxin-1, relaxin, and the most recently discovered relaxin-3 (Bathgate et al. 2013a; Halls et al. 2015). Relaxin-3 is classified by the presence of the characteristic RxxxRxxI/V relaxin-binding motif in the B-chain but otherwise has relatively low sequence homology to other relaxin peptides. Compared to other relaxins, relaxin-3 is well conserved across species (Wilkinson et al. 2005a; Yegorov et al. 2009), is believed to be the ancestral peptide (Wilkinson et al. 2005a), and in mammals is primarily a neuropeptide (Bathgate et al. 2002; Tanaka et al. 2005; Banerjee et al. 2010; Ma et al. 2007; McGowan et al. 2005; Ganella...

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References

  1. Ahren B. Islet G protein-coupled receptors as potential targets for treatment of type 2 diabetes. Nat Rev Drug Discov. 2009;8(5):369–85.PubMedPubMedCentralCrossRefGoogle Scholar
  2. Alvarez-Jaimes L, Sutton SW, Nepomuceno D, Motley ST, Cik M, Stocking E, et al. In vitro pharmacological characterization of RXFP3 allosterism: an example of probe dependency. PLoS One. 2012;7(2):e30792.PubMedPubMedCentralCrossRefGoogle Scholar
  3. Ang SY, Hutchinson DS, Patil N, Evans BA, Bathgate RA, Halls ML, et al. Signal transduction pathways activated by insulin-like peptide 5 at the relaxin family peptide RXFP4 receptor. Br J Pharmacol. 2016. doi 10.1111/bph.13522.Google Scholar
  4. Baker JG, Hill SJ. Multiple GPCR conformations and signalling pathways: implications for antagonist affinity estimates. Trends Pharmacol Sci. 2007;28(8):374–81.PubMedPubMedCentralCrossRefGoogle Scholar
  5. Banerjee A, Shen PJ, Ma S, Bathgate RA, Gundlach AL. Swim stress excitation of nucleus incertus and rapid induction of relaxin-3 expression via CRF1 activation. Neuropharmacology. 2010;58(1):145–55.PubMedPubMedCentralCrossRefGoogle Scholar
  6. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  7. Bathgate RA, Halls ML, van der Westhuizen ET, Callander GE, Kocan M, Summers RJ. Relaxin family peptides and their receptors. Physiol Rev. 2013a;93(1):405–80.PubMedPubMedCentralCrossRefGoogle Scholar
  8. Bathgate RA, Oh MH, Ling WJ, Kaas Q, Hossain MA, Gooley PR, et al. Elucidation of relaxin-3 binding interactions in the extracellular loops of RXFP3. Front Endocrinol. 2013b;4:13.CrossRefGoogle Scholar
  9. Belgi A, Hossain MA, Shabanpoor F, Chan L, Zhang S, Bathgate RA, et al. Structure and function relationship of murine insulin-like peptide 5 (INSL5): free C-terminus is essential for RXFP4 receptor binding and activation. Biochemistry. 2011;50(39):8352–61.PubMedPubMedCentralCrossRefGoogle Scholar
  10. Belgi A, Bathgate RA, Kocan M, Patil N, Zhang S, Tregear GW, et al. Minimum active structure of insulin-like peptide 5. J Med Chem. 2013;56(23):9509–16.PubMedPubMedCentralCrossRefGoogle Scholar
  11. Boels K, Schaller HC. Identification and characterisation of GPR100 as a novel human G-protein-coupled bradykinin receptor. Br J Pharmacol. 2003;140(5):932–8.PubMedPubMedCentralCrossRefGoogle Scholar
  12. Boels K, Hermans-Borgmeyer I, Schaller HC. Identification of a mouse orthologue of the G-protein-coupled receptor SALPR and its expression in adult mouse brain and during development. Brain Res Dev Brain Res. 2004;152(2):265–8.PubMedPubMedCentralCrossRefGoogle Scholar
  13. Burnicka-Turek O, Mohamed BA, Shirneshan K, Thanasupawat T, Hombach-Klonisch S, Klonisch T, et al. INSL5-deficient mice display an alteration in glucose homeostasis and an impaired fertility. Endocrinology. 2012;153(10):4655–65.PubMedPubMedCentralCrossRefGoogle Scholar
  14. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  15. 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;60:50–6.PubMedPubMedCentralCrossRefGoogle Scholar
  16. Davis RJ. Signal transduction by the JNK group of MAP kinases. Cell. 2000;103(2):239–52.PubMedPubMedCentralCrossRefGoogle Scholar
  17. Evans BA, Sato M, Sarwar M, Hutchinson DS, Summers RJ. Ligand-directed signalling at beta-adrenoceptors. Br J Pharmacol. 2010;159(5):1022–38.PubMedPubMedCentralCrossRefGoogle Scholar
  18. Ganella DE, Callander GE, Ma S, Bye CR, Gundlach AL, Bathgate RA. Modulation of feeding by chronic rAAV expression of a relaxin-3 peptide agonist in rat hypothalamus. Gene Ther. 2013a;20(7):703–16.PubMedPubMedCentralCrossRefGoogle Scholar
  19. Ganella DE, Ma S, Gundlach AL. Relaxin-3/RXFP3 signaling and neuroendocrine function – a perspective on extrinsic hypothalamic control. Front Endocrinol. 2013b;4:128.CrossRefGoogle Scholar
  20. Grosse J, Heffron H, Burling K, Akhter Hossain M, Habib AM, Rogers GJ, et al. Insulin-like peptide 5 is an orexigenic gastrointestinal hormone. Proc Natl Acad Sci U S A. 2014;111(30):11133–8.PubMedPubMedCentralCrossRefGoogle Scholar
  21. Halls ML, Bathgate RA, Sutton SW, Dschietzig TB, Summers RJ. International Union of Basic and Clinical Pharmacology. XCV. Recent advances in the understanding of the pharmacology and biological roles of relaxin family peptide receptors 1-4, the receptors for relaxin family peptides. Pharmacol Rev. 2015;67(2):389–440.PubMedPubMedCentralCrossRefGoogle Scholar
  22. Haugaard-Kedstrom LM, Shabanpoor F, Hossain MA, Clark RJ, Ryan PJ, Craik DJ, et al. Design, synthesis, and characterization of a single-chain peptide antagonist for the relaxin-3 receptor RXFP3. J Am Chem Soc. 2011;133(13):4965–74.PubMedPubMedCentralCrossRefGoogle Scholar
  23. Hida T, Takahashi E, Shikata K, Hirohashi T, Sawai T, Seiki T, et al. Chronic intracerebroventricular administration of relaxin-3 increases body weight in rats. J Recept Signal Transduct Res. 2006;26(3):147–58.PubMedPubMedCentralCrossRefGoogle Scholar
  24. Hosken IT, Sutton SW, Smith CM, Gundlach AL. Relaxin-3 receptor (Rxfp3) gene knockout mice display reduced running wheel activity: implications for role of relaxin-3/RXFP3 signalling in sustained arousal. Behav Brain Res. 2014;278:167–75.PubMedPubMedCentralCrossRefGoogle Scholar
  25. Hossain MA, Wade JD. The roles of the A- and B-chains of human relaxin-2 and -3 on their biological activity. Curr Protein Pept Sci. 2010;11(8):719–24.PubMedPubMedCentralCrossRefGoogle Scholar
  26. Hossain MA, Rosengren KJ, Haugaard-Jonsson LM, Zhang S, Layfield S, Ferraro T, et al. The A-chain of human relaxin family peptides has distinct roles in the binding and activation of the different relaxin family peptide receptors. J Biol Chem. 2008;283(25):17287–97.PubMedPubMedCentralCrossRefGoogle Scholar
  27. Hossain MA, Bathgate RA, Rosengren KJ, Shabanpoor F, Zhang S, Lin F, et al. The structural and functional role of the B-chain C-terminal arginine in the relaxin-3 peptide antagonist, R3(BDelta23-27)R/I5. Chem Biol Drug Des. 2009;73(1):46–52.PubMedPubMedCentralCrossRefGoogle Scholar
  28. Kenakin T, Miller LJ. Seven transmembrane receptors as shapeshifting proteins: the impact of allosteric modulation and functional selectivity on new drug discovery. Pharmacol Rev. 2010;62(2):265–304.PubMedPubMedCentralCrossRefGoogle Scholar
  29. Kocan M, Sarwar M, Hossain MA, Wade JD, Summers RJ. Signalling profiles of H3 relaxin, H2 relaxin and R3(BDelta23-27)R/I5 acting at the relaxin family peptide receptor 3 (RXFP3). Br J Pharmacol. 2014;171(11):2827–41.PubMedPubMedCentralCrossRefGoogle Scholar
  30. Kuei C, Sutton S, Bonaventure P, Pudiak C, Shelton J, Zhu J, et al. R3(BDelta23 27)R/I5 chimeric peptide, a selective antagonist for GPCR135 and GPCR142 over relaxin receptor LGR7: in vitro and in vivo characterization. J Biol Chem. 2007;282(35):25425–35.PubMedPubMedCentralCrossRefGoogle Scholar
  31. 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. 2003a;278(50):50754–64.PubMedPubMedCentralCrossRefGoogle Scholar
  32. 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. 2003b;278(50):50765–70.PubMedPubMedCentralCrossRefGoogle Scholar
  33. Liu C, Kuei C, Sutton S, Chen J, Bonaventure P, Wu J, et al. INSL5 is a high affinity specific agonist for GPCR142 (GPR100). J Biol Chem. 2005a;280(1):292–300.PubMedPubMedCentralCrossRefGoogle Scholar
  34. Liu C, Chen J, Kuei C, Sutton S, Nepomuceno 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. 2005b;67(1):231–40.PubMedPubMedCentralCrossRefGoogle Scholar
  35. 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(1):165–90.PubMedPubMedCentralCrossRefGoogle Scholar
  36. Ma S, Olucha-Bordonau FE, Hossain MA, Lin F, Kuei C, Liu C, et al. Modulation of hippocampal theta oscillations and spatial memory by relaxin-3 neurons of the nucleus incertus. Learn Mem. 2009;16(11):730–42.PubMedPubMedCentralCrossRefGoogle Scholar
  37. Mashima H, Ohno H, Yamada Y, Sakai T, Ohnishi H. INSL5 may be a unique marker of colorectal endocrine cells and neuroendocrine tumors. Biochem Biophys Res Commun. 2013;432(4):586–92.PubMedPubMedCentralCrossRefGoogle Scholar
  38. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  39. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  40. McGowan BM, Stanley SA, Smith KL, Minnion JS, Donovan J, Thompson EL, et al. Effects of acute and chronic relaxin-3 on food intake and energy expenditure in rats. Regul Pept. 2006;136:72–7.PubMedPubMedCentralCrossRefGoogle Scholar
  41. Morikawa Y, Ueyama E, Senba E. Fasting-induced activation of mitogen-activated protein kinases (ERK/p38) in the mouse hypothalamus. J Neuroendocrinol. 2004;16(2):105–12.PubMedPubMedCentralCrossRefGoogle Scholar
  42. Munro J, Skrobot O, Sanyoura M, Kay V, Susce MT, Glaser PE, et al. Relaxin polymorphisms associated with metabolic disturbance in patients treated with antipsychotics. J Psychopharmacol. 2012;26(3):374–9.PubMedPubMedCentralCrossRefGoogle Scholar
  43. Nunez A, Cervera-Ferri A, Olucha-Bordonau F, Ruiz-Torner A, Teruel V. Nucleus incertus contribution to hippocampal theta rhythm generation. Eur J Neurosci. 2006;23(10):2731–8.PubMedPubMedCentralCrossRefGoogle Scholar
  44. Olucha-Bordonau FE, Teruel V, Barcia-Gonzalez J, Ruiz-Torner A, Valverde-Navarro AA, Martinez-Soriano F. Cytoarchitecture and efferent projections of the nucleus incertus of the rat. J Comp Neurol. 2003;464(1):62–97.PubMedPubMedCentralCrossRefGoogle Scholar
  45. Patil NA, Hughes RA, Rosengren KJ, Kocan M, Ang SY, Tailhades J, et al. Engineering of a novel simplified human insulin-like peptide 5 agonist. J Med Chem. 2016;59:2118–2125.PubMedPubMedCentralCrossRefGoogle Scholar
  46. Price MA, Cruzalegui FH, Treisman R. The p38 and ERK MAP kinase pathways cooperate to activate Ternary Complex Factors and c-fos transcription in response to UV light. EMBO J. 1996;15(23):6552–63.PubMedPubMedCentralCrossRefGoogle Scholar
  47. Rosengren KJ, Zhang S, Lin F, Daly NL, Scott DJ, Hughes RA, et al. Solution structure and characterization of the LGR8 receptor binding surface of insulin-like peptide 3. J Biol Chem. 2006a;281(38):28287–95.PubMedPubMedCentralCrossRefGoogle Scholar
  48. Rosengren KJ, Lin F, Bathgate RA, Tregear GW, Daly NL, Wade JD, et al. Solution structure and novel insights into the determinants of the receptor specificity of human relaxin-3. J Biol Chem. 2006b;281(9):5845–51.PubMedPubMedCentralCrossRefGoogle Scholar
  49. Roux PP, Blenis J. ERK and p38 MAPK-activated protein kinases: a family of protein kinases with diverse biological functions. Microbiol Mol Biol Rev. 2004;68(2):320–44.PubMedPubMedCentralCrossRefGoogle Scholar
  50. Ryan PJ, Buchler E, Shabanpoor F, Hossain MA, Wade JD, Lawrence AJ, et al. Central relaxin-3 receptor (RXFP3) activation decreases anxiety- and depressive-like behaviours in the rat. Behav Brain Res. 2013a;244:142–51.PubMedPubMedCentralCrossRefGoogle Scholar
  51. Ryan PJ, Kastman HE, Krstew EV, Rosengren KJ, Hossain MA, Churilov L, et al. Relaxin-3/RXFP3 system regulates alcohol-seeking. Proc Natl Acad Sci U S A. 2013b;110(51):20789–94.PubMedPubMedCentralCrossRefGoogle Scholar
  52. Sasaguri K, Kikuchi M, Hori N, Yuyama N, Onozuka M, Sato S. Suppression of stress immobilization-induced phosphorylation of ERK 1/2 by biting in the rat hypothalamic paraventricular nucleus. Neurosci Lett. 2005;383(1–2):160–4.PubMedPubMedCentralCrossRefGoogle Scholar
  53. Scott DJ, Fu P, Shen PJ, Gundlach A, Layfield S, Riesewijk A, et al. Characterization of the rat INSL3 receptor. Ann N Y Acad Sci. 2005;1041:13–6.PubMedPubMedCentralCrossRefGoogle Scholar
  54. Shabanpoor F, Akhter Hossain M, Ryan PJ, Belgi A, Layfield S, Kocan M, et al. Minimization of human relaxin-3 leading to high-affinity analogues with increased selectivity for relaxin-family peptide 3 receptor (RXFP3) over RXFP1. J Med Chem. 2012;55(4):1671–81.PubMedPubMedCentralCrossRefGoogle Scholar
  55. Shen CP, Tsimberg Y, Salvadore C, Meller E. Activation of Erk and JNK MAPK pathways by acute swim stress in rat brain regions. BMC Neurosci. 2004;5(1):36.PubMedPubMedCentralCrossRefGoogle Scholar
  56. Smith CM, Lawrence AJ, Sutton SW, Gundlach AL. Behavioral phenotyping of mixed background (129S5:B6) relaxin-3 knockout mice. Ann N Y Acad Sci. 2009;1160:236–41.PubMedPubMedCentralCrossRefGoogle Scholar
  57. Smith CM, Shen PJ, Banerjee A, Bonaventure P, Ma S, Bathgate RA, et al. Distribution of relaxin-3 and RXFP3 within arousal, stress, affective, and cognitive circuits of mouse brain. J Comp Neurol. 2010;518(19):4016–45.PubMedPubMedCentralCrossRefGoogle Scholar
  58. Smith CM, Ryan PJ, Hosken IT, Ma S, Gundlach AL. Relaxin-3 systems in the brain-The first 10 years. J Chem Neuroanat. 2011;42:262–75.PubMedPubMedCentralCrossRefGoogle Scholar
  59. Smith CM, Chua BE, Zhang C, Walker AW, Haidar M, Hawkes D, et al. Central injection of relaxin-3 receptor (RXFP3) antagonist peptides reduces motivated food seeking and consumption in C57BL/6 J mice. Behav Brain Res. 2014;268:117–26.PubMedPubMedCentralCrossRefGoogle Scholar
  60. Sudo S, Kumagai J, Nishi S, Layfield S, Ferraro T, Bathgate RA, et al. H3 relaxin is a specific ligand for LGR7 and activates the receptor by interacting with both the ectodomain and the exoloop 2. J Biol Chem. 2003;278(10):7855–62.PubMedPubMedCentralCrossRefGoogle Scholar
  61. Sutton RE, Koob GF, Le Moal M, Rivier J, Vale W. Corticotropin releasing factor produces behavioural activation in rats. Nature. 1982;297(5864):331–3.PubMedPubMedCentralCrossRefGoogle Scholar
  62. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  63. Sutton SW, Shelton J, Smith C, Williams J, Yun S, Motley T, et al. Metabolic and neuroendocrine responses to RXFP3 modulation in the central nervous system. Ann N Y Acad Sci. 2009;1160:242–9.PubMedPubMedCentralCrossRefGoogle Scholar
  64. 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(6):1659–70.PubMedPubMedCentralCrossRefGoogle Scholar
  65. Thanasupawat T, Hammje K, Adham I, Ghia JE, Del Bigio MR, Krcek J, et al. INSL5 is a novel marker for human enteroendocrine cells of the large intestine and neuroendocrine tumours. Oncol Rep. 2013;29(1):149–54.PubMedPubMedCentralCrossRefGoogle Scholar
  66. Van der Westhuizen ET. Molecular characterisation of human and mouse relaxin-3 receptors (RXFP3) in recombinant and endogenously expressing cell lines. Melbourne: Monash University; 2008.Google Scholar
  67. Van Der Westhuizen E, Sexton PM, Bathgate RA, Summers RJ. Responses of GPCR135 to human gene 3 (H3) relaxin in CHO-K1 cells determined by microphysiometry. Ann N Y Acad Sci. 2005;1041:332–7.PubMedPubMedCentralCrossRefGoogle Scholar
  68. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  69. 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(5):759–72.PubMedPubMedCentralCrossRefGoogle Scholar
  70. Whitmarsh AJ, Davis RJ. Transcription factor AP-1 regulation by mitogen-activated protein kinase signal transduction pathways. J Mol Med. 1996;74(10):589–607.PubMedPubMedCentralCrossRefGoogle Scholar
  71. Wilkinson TN, Speed TP, Tregear GW, Bathgate RA. Evolution of the relaxin-like peptide family. BMC Evol Biol. 2005a;5(1):14.PubMedPubMedCentralCrossRefGoogle Scholar
  72. Wilkinson TN, Speed TP, Tregear GW, Bathgate RA. Coevolution of the relaxin-like peptides and their receptors. Ann N Y Acad Sci. 2005b;1041:534–9.PubMedPubMedCentralCrossRefGoogle Scholar
  73. Wu B, Chien EY, Mol CD, Fenalti G, Liu W, Katritch V, et al. Structures of the CXCR4 chemokine GPCR with small-molecule and cyclic peptide antagonists. Science. 2010;330(6007):1066–71.PubMedPubMedCentralCrossRefGoogle Scholar
  74. Yamamoto H, Arai T, Tasaka R, Mori Y, Iguchi K, Unno K, et al. Inhibitory effect of relaxin-3 on insulin secretion in isolated pancreas and insulinoma. J Health Sci. 2009;55(1):132–7.CrossRefGoogle Scholar
  75. Yegorov S, Good-Avila SV, Parry L, Wilson BC. Relaxin family genes in humans and teleosts. Ann N Y Acad Sci. 2009;1160:42–4.PubMedPubMedCentralCrossRefGoogle Scholar
  76. Zhang X, Zhu M, Zhao M, Chen W, Fu Y, Liu Y, et al. The plasma levels of relaxin-2 and relaxin-3 in patients with diabetes. Clin Biochem. 2013;46(16–17):1713–6.PubMedPubMedCentralCrossRefGoogle Scholar
  77. Zhang WJ, Wang XY, Guo YQ, Luo X, Gao XJ, Shao XX, et al. The highly conserved negatively charged Glu141 and Asp145 of the G-protein-coupled receptor RXFP3 interact with the highly conserved positively charged arginine residues of relaxin-3. Amino Acids. 2014;46:1393–402.PubMedPubMedCentralCrossRefGoogle Scholar
  78. 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.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  • Martina Kocan
    • 1
  • Sheng Yu Ang
    • 2
  • Roger J. Summers
    • 2
  1. 1.Neuropeptides Division, Florey Institute of Neuroscience and Mental Health and Department of Biochemistry and Molecular Biology, University of MelbourneParkvilleAustralia
  2. 2.Drug Discovery Biology, Monash Institute of Pharmaceutical SciencesMonash UniversityParkvilleAustralia