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Gene Review

RXFP2  -  relaxin/insulin-like family peptide...

Homo sapiens

Synonyms: G-protein coupled receptor 106, G-protein coupled receptor affecting testicular descent, GPR106, GREAT, INSL3R, ...
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Disease relevance of RXFP2


Psychiatry related information on RXFP2


High impact information on RXFP2


Chemical compound and disease context of RXFP2

  • BACKGROUND & AIMS: Acetaminophen toxicity is the most common cause of acute liver failure (ALF) in the United States and Great Britain, but may be underrecognized in certain settings [15].
  • One major observation of this literature search is that permethrin is the treatment of choice for lice and scabies in the US and in Great Britain, whereas lindane is still recommended for scabies in most other European countries because of its longer-standing record of effectiveness [16].
  • Seasonal incidence of Vibrio vulnificus in the Great Bay estuary of New Hampshire and Maine [17].
  • CONCLUSION: Great caution should be exercised in the post hoc interpretation of the potential efficacy of nonrandomized treatments such as heparin therapy derived from phase III clinical data of other drugs for sepsis [18].
  • Angiosarcoma of the liver: a marker tumour for the late effects of Thorotrast in Great Britain [19].

Biological context of RXFP2


Anatomical context of RXFP2


Associations of RXFP2 with chemical compounds

  • Activation of RXFP1 or RXFP2 causes increased cAMP and the initial response for both receptors is the resultant of Gs-mediated activation and G(oB)-mediated inhibition of adenylate cyclase [2].
  • All-trans-retinoic acid was demonstrated in PC-3 to up-regulate LGR8 gene activity in a dose- and time-dependent manner while having no effect on INSL3 gene activity [24].
  • In the anaplastic thyroid carcinoma cell line 8505C, the regulation of both INSL-3 and LGR8 by estrogen may be the first indication of a novel hormonally responsive, auto-/paracrine INSL-3 LGR8 ligand receptor system active in human thyroid carcinoma cells [23].
  • Alanine-substituted analogs were used to identify the key residues of INSL3 that are responsible for the interaction with the ectodomain of LGR8 [27].
  • Our latest studies of RLF and LGR8 have revealed that the N-terminal region of the A chain is not required for receptor binding but is indispensable for cyclic AMP generation [28].
  • Our results show that negative cooperativity is present and that INSL3-RXFP2 binding shows both similarities and differences with insulin binding to the insulin receptor [29].

Physical interactions of RXFP2


Regulatory relationships of RXFP2

  • To this end, we examined the effect of stimulation of RXFP1 and RXFP2 receptors [expressed in human embryonic kidney (HEK) 293T cells] with human relaxin family peptides on a number of transcription factor-response elements coupled to reporter genes [20].
  • In addition to expressing INSL3 mRNA, the LGR8-negative DU-145 also expressed an INSL3 splice form formerly demonstrated in thyroid carcinoma cells [24].
  • A postal survey of pharmacists in a random sample of community pharmacies in Great Britain was carried out to ascertain the factors which influenced their decisions when recommending a product for Over The Counter (OTC) sale [30].

Other interactions of RXFP2

  • Comparison of Signaling Pathways Activated by the Relaxin Family Peptide Receptors, RXFP1 and RXFP2, Using Reporter Genes [20].
  • RXFP1 and RXFP2 receptors produce increases in intracellular cAMP levels upon stimulation, although the response is complex and contains a component sensitive to PI-3-kinase inhibitors [31].
  • In addition, INSL5 (up to 1 microm) shows no affinity or activity at LGR7 or LGR8 either in a binding assay or a bio-functional assay [32].
  • Recent studies have demonstrated that relaxin-3 will bind to and activate human LGR7, but not LGR8, in vitro [33].
  • The reporter gene studies suggest that ligand stimulation of LGR7 and LGR8 involves cAMP-PKA and p38/JNK signaling [34].

Analytical, diagnostic and therapeutic context of RXFP2

  • Northern blot analysis indicated that the LGR8 transcripts are expressed in gubernaculum whereas treatment of cultured gubernacular cells with INSL3 stimulated cAMP production and thymidine incorporation [35].
  • Using a combination of mRNA analysis by RT-PCR, immunohistochemistry, ligand-binding, and/or bioactivity assays, the distribution of LGR8 expression was assessed in testicular tissues and cells and in the epididymis [36].
  • Quantitative, real-time PCR analysis of the developmental profile of Lgr8 mRNA expression in kidney revealed highest relative levels at late stage gestation (embryonic day 18), with a sharp decrease after birth and lowest levels in the adult [37].
  • Thus, using in situ hybridization histochemistry, cells expressing Lgr8 mRNA were observed in glomeruli of renal cortex from adult rats and were tentatively identified as mesangial cells [37].
  • Both peptides exhibited similar, but high, receptor binding affinities on human foetal kidney fibroblast 293T cells transfected human LGR8 based on a competition radioreceptor assay with 33P-labelled relaxin H2 (B33) [38].


  1. International Union of Pharmacology LVII: recommendations for the nomenclature of receptors for relaxin family peptides. Bathgate, R.A., Ivell, R., Sanborn, B.M., Sherwood, O.D., Summers, R.J. Pharmacol. Rev. (2006) [Pubmed]
  2. Relaxin Family Peptide Receptors - former orphans reunite with their parent ligands to activate multiple signalling pathways. Halls, M.L., van der Westhuizen, E.T., Bathgate, R.A., Summers, R.J. Br. J. Pharmacol. (2007) [Pubmed]
  3. Restricted expression of LGR8 in intralaminar thalamic nuclei of rat brain suggests a role in sensorimotor systems. Shen, P.J., Fu, P., Phelan, K.D., Scott, D.J., Layfield, S., Tregear, G.W., Bathgate, R.A., Gundlach, A.L. Ann. N. Y. Acad. Sci. (2005) [Pubmed]
  4. Nitrates, nitrites and gastric cancer in Great Britain. Forman, D., Al-Dabbagh, S., Doll, R. Nature (1985) [Pubmed]
  5. Tamoxifen. Use in treatment of metastatic breast cancer refractory to combination chemotherapy. Legha, S.S., Buzdar, A.U., Hortobagyi, G.N., Wiseman, C., Benjamin, R.S., Blumenschein, G.R. JAMA (1979) [Pubmed]
  6. Chemical defense mechanisms on the Great Barrier Reef, Australia. Bakus, G.J. Science (1981) [Pubmed]
  7. The risk of bovine spongiform encephalopathy ('mad cow disease') to human health. Brown, P. JAMA (1997) [Pubmed]
  8. The Great Smoky Mountains Study of Youth. Goals, design, methods, and the prevalence of DSM-III-R disorders. Costello, E.J., Angold, A., Burns, B.J., Stangl, D.K., Tweed, D.L., Erkanli, A., Worthman, C.M. Arch. Gen. Psychiatry (1996) [Pubmed]
  9. The Great Smoky Mountains Study of Youth. Functional impairment and serious emotional disturbance. Costello, E.J., Angold, A., Burns, B.J., Erkanli, A., Stangl, D.K., Tweed, D.L. Arch. Gen. Psychiatry (1996) [Pubmed]
  10. Obsessive-compulsive disorder: prevalence, comorbidity, impact, and help-seeking in the british national psychiatric morbidity survey of 2000. Torres, A.R., Prince, M.J., Bebbington, P.E., Bhugra, D., Brugha, T.S., Farrell, M., Jenkins, R., Lewis, G., Meltzer, H., Singleton, N. The American journal of psychiatry. (2006) [Pubmed]
  11. Chernobyl nuclide record from a North Sea sediment trap. Kempe, S., Nies, H. Nature (1987) [Pubmed]
  12. N-formyliminodiacetic acid, a new compound from the reaction of nitrilotriacetic acid and chlorine. Spanggord, R.J., Tyson, C.A. Science (1979) [Pubmed]
  13. Toxic fungi. Lampe, K.F. Annu. Rev. Pharmacol. Toxicol. (1979) [Pubmed]
  14. Sleeping prone and the risk of sudden infant death syndrome. Guntheroth, W.G., Spiers, P.S. JAMA (1992) [Pubmed]
  15. Measurement of serum acetaminophen-protein adducts in patients with acute liver failure. Davern, T.J., James, L.P., Hinson, J.A., Polson, J., Larson, A.M., Fontana, R.J., Lalani, E., Munoz, S., Shakil, A.O., Lee, W.M. Gastroenterology (2006) [Pubmed]
  16. Pharmacotherapy of ectoparasitic infections. Roos, T.C., Alam, M., Roos, S., Merk, H.F., Bickers, D.R. Drugs (2001) [Pubmed]
  17. Seasonal incidence of Vibrio vulnificus in the Great Bay estuary of New Hampshire and Maine. O'Neill, K.R., Jones, S.H., Grimes, D.J. Appl. Environ. Microbiol. (1992) [Pubmed]
  18. Unintended bias, clinical trial results, and the heparin post hoc crossover fallacy. Opal, S.M. Crit. Care Med. (2004) [Pubmed]
  19. Angiosarcoma of the liver: a marker tumour for the late effects of Thorotrast in Great Britain. Baxter, P.J., Langlands, A.O., Anthony, P.P., Macsween, R.N., Scheuer, P.J. Br. J. Cancer (1980) [Pubmed]
  20. Comparison of Signaling Pathways Activated by the Relaxin Family Peptide Receptors, RXFP1 and RXFP2, Using Reporter Genes. Halls, M.L., Bathgate, R.A., Summers, R.J. J. Pharmacol. Exp. Ther. (2007) [Pubmed]
  21. Multiple binding sites revealed by interaction of relaxin family peptides with native and chimeric relaxin family peptide receptors 1 and 2 (LGR7 and LGR8). Halls, M.L., Bond, C.P., Sudo, S., Kumagai, J., Ferraro, T., Layfield, S., Bathgate, R.A., Summers, R.J. J. Pharmacol. Exp. Ther. (2005) [Pubmed]
  22. Relaxin research in the postgenomic era. Kawamura, K., Sudo, S., Kumagai, J., Pisarska, M., Hsu, S.Y., Bathgate, R., Wade, J., Hsueh, A.J. Ann. N. Y. Acad. Sci. (2005) [Pubmed]
  23. INSL-3 is expressed in human hyperplastic and neoplastic thyrocytes. Hombach-Klonisch, S., Hoang-Vu, C., Kehlen, A., Hinze, R., Holzhausen, H.J., Weber, E., Fischer, B., Dralle, H., Klonisch, T. Int. J. Oncol. (2003) [Pubmed]
  24. INSL3 in the benign hyperplastic and neoplastic human prostate gland. Klonisch, T., Müller-Huesmann, H., Riedel, M., Kehlen, A., Bialek, J., Radestock, Y., Holzhausen, H.J., Steger, K., Ludwig, M., Weidner, W., Hoang-Vu, C., Hombach-Klonisch, S. Int. J. Oncol. (2005) [Pubmed]
  25. Mutations of the GREAT gene cause cryptorchidism. Gorlov, I.P., Kamat, A., Bogatcheva, N.V., Jones, E., Lamb, D.J., Truong, A., Bishop, C.E., McElreavey, K., Agoulnik, A.I. Hum. Mol. Genet. (2002) [Pubmed]
  26. The INSL3-LGR8/GREAT ligand-receptor pair in human cryptorchidism. Ferlin, A., Simonato, M., Bartoloni, L., Rizzo, G., Bettella, A., Dottorini, T., Dallapiccola, B., Foresta, C. J. Clin. Endocrinol. Metab. (2003) [Pubmed]
  27. Solution Structure and Characterization of the LGR8 Receptor Binding Surface of Insulin-like Peptide 3. Rosengren, K.J., Zhang, S., Lin, F., Daly, N.L., Scott, D.J., Hughes, R.A., Bathgate, R.A., Craik, D.J., Wade, J.D. J. Biol. Chem. (2006) [Pubmed]
  28. LGR8 signal activation by the relaxin-like factor. Büllesbach, E.E., Schwabe, C. J. Biol. Chem. (2005) [Pubmed]
  29. Cooperative binding of insulin-like Peptide 3 to a dimeric relaxin family peptide receptor 2. Svendsen, A.M., Vrecl, M., Ellis, T.M., Heding, A., Kristensen, J.B., Wade, J.D., Bathgate, R.A., De Meyts, P., Nøhr, J. Endocrinology (2008) [Pubmed]
  30. An investigation of the factors affecting community pharmacists' selection of over the counter preparations. Kennedy, E., Moody, M. Pharmacy world & science : PWS. (2000) [Pubmed]
  31. Receptors for relaxin family peptides. Bathgate, R.A., Ivell, R., Sanborn, B.M., Sherwood, O.D., Summers, R.J. Ann. N. Y. Acad. Sci. (2005) [Pubmed]
  32. INSL5 is a high affinity specific agonist for GPCR142 (GPR100). Liu, C., Kuei, C., Sutton, S., Chen, J., Bonaventure, P., Wu, J., Nepomuceno, D., Kamme, F., Tran, D.T., Zhu, J., Wilkinson, T., Bathgate, R., Eriste, E., Sillard, R., Lovenberg, T.W. J. Biol. Chem. (2005) [Pubmed]
  33. The chemistry and biology of human relaxin-3. Tregear, G.W., Bathgate, R.A., Layfield, S., Ferraro, T., Gundlach, A., Ma, S., Lin, F., Hanson, N.F., Summers, R.J., Rosengren, J., Craik, D.J., Wade, J.D. Ann. N. Y. Acad. Sci. (2005) [Pubmed]
  34. Signaling pathways of the LGR7 and LGR8 receptors determined by reporter genes. Halls, M.L., Bathgate, R.A., Roche, P.J., Summers, R.J. Ann. N. Y. Acad. Sci. (2005) [Pubmed]
  35. INSL3/Leydig insulin-like peptide activates the LGR8 receptor important in testis descent. Kumagai, J., Hsu, S.Y., Matsumi, H., Roh, J.S., Fu, P., Wade, J.D., Bathgate, R.A., Hsueh, A.J. J. Biol. Chem. (2002) [Pubmed]
  36. Expression of the Insulin-Like Peptide 3 (INSL3) Hormone-Receptor (LGR8) System in the Testis. Anand-Ivell, R.J., Relan, V., Balvers, M., Coiffec-Dorval, I., Fritsch, M., Bathgate, R.A., Ivell, R. Biol. Reprod. (2006) [Pubmed]
  37. Leucine-rich repeat-containing G-protein-coupled receptor 8 in mature glomeruli of developing and adult rat kidney and inhibition by insulin-like peptide-3 of glomerular cell proliferation. Fu, P., Shen, P.J., Zhao, C.X., Scott, D.J., Samuel, C.S., Wade, J.D., Tregear, G.W., Bathgate, R.A., Gundlach, A.L. J. Endocrinol. (2006) [Pubmed]
  38. Synthesis, conformation, receptor binding and biological activities of monobiotinylated human insulin-like peptide 3. Fu, P., Layfield, S., Ferraro, T., Tomiyama, H., Hutson, J., Otvos, L., Tregear, G.W., Bathgate, R.A., Wade, J.D. J. Pept. Res. (2004) [Pubmed]
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