RXFP3

Summary

Gene Symbol: RXFP3
Description: relaxin/insulin-like family peptide receptor 3
Alias: GPCR135, RLN3R1, RXFPR3, SALPR, G-protein coupled receptor GPCR135, G-protein coupled receptor SALPR, RLN3 receptor 1, g protein-coupled receptor SALPR, relaxin 3 receptor 1, relaxin family peptide receptor 3, relaxin-3 receptor 1, somatostatin and angiotensin-like peptide receptor, somatostatin- and angiotensin-like peptide receptor
Species: human

Top Publications

  1. ncbi 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
    Steven W Sutton
    Neuroscience Group, Johnson and Johnson Pharmaceutical Research and Development, LLC, 3210 Merryfield Row, San Diego, CA 92121, USA
    Neuroendocrinology 80:298-307. 2004
  2. ncbi Fine mapping of the 5p13 locus linked to schizophrenia and schizotypal personality disorder in a Puerto Rican family
    Irina N Bespalova
    Department of Psychiatry, Mount Sinai School of Medicine, New York, NY 10029, USA
    Psychiatr Genet 15:205-10. 2005
  3. ncbi Relaxin-3: improved synthesis strategy and demonstration of its high-affinity interaction with the relaxin receptor LGR7 both in vitro and in vivo
    Ross A D Bathgate
    Howard Florey Institute, University of Melbourne, Melbourne, Victoria 3010, Australia
    Biochemistry 45:1043-53. 2006
  4. doi Roles of the receptor, the ligand, and the cell in the signal transduction pathways utilized by the relaxin family peptide receptors 1-3
    Roger J Summers
    Department of Pharmacology, Monash Institute of Pharmaceutical Sciences, Monash University, Clayton, Victoria, Australia
    Ann N Y Acad Sci 1160:99-104. 2009
  5. ncbi International Union of Pharmacology LVII: recommendations for the nomenclature of receptors for relaxin family peptides
    Ross A Bathgate
    Howard Florey Institute, University of Melbourne, Victoria, Australia
    Pharmacol Rev 58:7-31. 2006
  6. ncbi The novel G-protein coupled receptor SALPR shares sequence similarity with somatostatin and angiotensin receptors
    M Matsumoto
    Molecular Medicine Laboratories, Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co, Ltd, 21 Miyukigaoka, Tsukuba, Ibaraki, Japan
    Gene 248:183-9. 2000
  7. ncbi 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
    Changlu Liu
    Johnson and Johnson Pharmaceutical Research and Development, L L C, San Diego, CA 92121, USA
    Mol Pharmacol 67:231-40. 2005
  8. ncbi Identification of relaxin-3/INSL7 as an endogenous ligand for the orphan G-protein-coupled receptor GPCR135
    Changlu Liu
    Johnson and Johnson Pharmaceutical Research and Development, L L C, San Diego, California 92121, USA
    J Biol Chem 278:50754-64. 2003
  9. ncbi Relaxin receptors--new drug targets for multiple disease states
    E T van der Westhuizen
    Department of Pharmacology, Monash University, Wellington Road, Clayton, Victoria 3800, Australia
    Curr Drug Targets 8:91-104. 2007
  10. ncbi 'Relaxin' the stiffened heart and arteries: the therapeutic potential for relaxin in the treatment of cardiovascular disease
    Chrishan S Samuel
    Howard Florey Institute, University of Melbourne, Victoria 3010, Australia Department of Biochemistry and Molecular Biology, University of Melbourne, Victoria 3010, Australia
    Pharmacol Ther 112:529-52. 2006

Research Grants

  1. PHYSIOLOGY OF RELAXIN-INSULIN-LIKE FACTORS
    Sheau Yu Hsu; Fiscal Year: 2002
  2. Identification of Relaxin Receptor Antagonists
    Sheau Yu Hsu; Fiscal Year: 2005
  3. Role of RAMPs in Intermedin Signaling
    Sheau Yu Hsu; Fiscal Year: 2009
  4. Role of RAMPs in Intermedin Signaling
    Sheau Yu Teddy Hsu; Fiscal Year: 2010

Scientific Experts

  • B C Wilson
  • Changlu Liu
  • Steven W Sutton
  • R J Summers
  • Sherie Ma
  • Andrew L Gundlach
  • Thomas Dschietzig
  • Masaki Tanaka
  • Irina N Bespalova
  • K Johan Rosengren
  • John D Wade
  • SHEAU-YU T HSU
  • Mitsuyuki Matsumoto
  • Ross A D Bathgate
  • Mohammed Akhter Hossain
  • Philip J Ryan
  • Emma T Van der Westhuizen
  • Geoffrey W Tregear
  • Fazel Shabanpoor
  • Craig M Smith
  • Wei Jie Zhang
  • Chrishan S Samuel
  • Linda M Haugaard-Jönsson
  • Suode Zhang
  • Xiao Xia Shao
  • Zhan Yun Guo
  • Xiao Luo
  • R A D Bathgate
  • M L Halls
  • E T van der Westhuizen
  • Patrick M Sexton
  • Pascal Bonaventure
  • B M McGowan
  • Feng Lin
  • Chester Kuei
  • Tracey N Wilkinson
  • Ross A Bathgate
  • Sharon Layfield
  • David J Craik
  • Norelle L Daly
  • Katrin Boels
  • Jessica Zhu
  • S R Bloom
  • Timothy W Lovenberg
  • M A Ghatei
  • E L Thompson
  • S A Stanley
  • J V Gardiner
  • Valeria Cernaro
  • Jingcai Chen
  • Anna Blasiak
  • Andrew J Lawrence
  • Elena Büchler
  • Ramamoorthy Rajkumar
  • Ge Song
  • Xin Yi Wang
  • Janet Munro
  • Despina E Ganella
  • Paul R Gooley
  • Linda M Haugaard-Kedström
  • Ya Li Liu
  • Yi Wen Huang
  • Roy C K Kong
  • Pei Juan Shen
  • Barbara M C McGowan
  • Xiao Jun Du
  • Chongxin Zhao
  • M Patterson
  • John Atack
  • Fredrik Kamme
  • J Donovan
  • Tania Ferraro
  • K G Murphy
  • N E White
  • K L Smith
  • Diane Nepomuceno
  • O David Sherwood
  • Richard Ivell
  • Barbara M Sanborn
  • Stefanie Ortinau
  • Tanya C D Burazin
  • B M C McGowan
  • H Chica Schaller
  • Davide Bolignano
  • Michele Buemi
  • Domenico Trimboli
  • Antonio Lacquaniti
  • Rosaria Lupica
  • Antoine Buemi
  • Grazia Giorgianni

Detail Information

Publications79

  1. ncbi 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
    Steven W Sutton
    Neuroscience Group, Johnson and Johnson Pharmaceutical Research and Development, LLC, 3210 Merryfield Row, San Diego, CA 92121, USA
    Neuroendocrinology 80:298-307. 2004
    G-protein-coupled receptor 135 (GPCR135), a former orphan GPCR also known as SALPR, has recently been shown to be modulated by relaxin-3 (R3)...
  2. ncbi Fine mapping of the 5p13 locus linked to schizophrenia and schizotypal personality disorder in a Puerto Rican family
    Irina N Bespalova
    Department of Psychiatry, Mount Sinai School of Medicine, New York, NY 10029, USA
    Psychiatr Genet 15:205-10. 2005
    ..8 Mb. G-protein-coupled receptor gene [somatostatin and angiotensin-like peptide receptor (SALPR)] is one of the candidate genes within the critical interval...
  3. ncbi Relaxin-3: improved synthesis strategy and demonstration of its high-affinity interaction with the relaxin receptor LGR7 both in vitro and in vivo
    Ross A D Bathgate
    Howard Florey Institute, University of Melbourne, Melbourne, Victoria 3010, Australia
    Biochemistry 45:1043-53. 2006
    ..Although the highest activity was demonstrated on the human relaxin-3 receptor (GPCR135), the peptide also showed high activity on relaxin receptors (LGR7) from various species and variable activity on ..
  4. doi Roles of the receptor, the ligand, and the cell in the signal transduction pathways utilized by the relaxin family peptide receptors 1-3
    Roger J Summers
    Department of Pharmacology, Monash Institute of Pharmaceutical Sciences, Monash University, Clayton, Victoria, Australia
    Ann N Y Acad Sci 1160:99-104. 2009
    ..RXFP1 and 2 are characterized by large extracellular domains containing leucine-rich repeats, whereas RXFP3 and 4 closely resemble small-peptide-liganded GPCRs...
  5. ncbi International Union of Pharmacology LVII: recommendations for the nomenclature of receptors for relaxin family peptides
    Ross A Bathgate
    Howard Florey Institute, University of Melbourne, Victoria, Australia
    Pharmacol Rev 58:7-31. 2006
    ..the receptors for relaxin (LGR7) and those for the related peptides insulin-like peptide 3 (LGR8), relaxin-3 (GPCR135), and insulin-like peptide 5 (LGPCR142) be named the relaxin family peptide receptors 1 through 4 (RXFP1-4)...
  6. ncbi The novel G-protein coupled receptor SALPR shares sequence similarity with somatostatin and angiotensin receptors
    M Matsumoto
    Molecular Medicine Laboratories, Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co, Ltd, 21 Miyukigaoka, Tsukuba, Ibaraki, Japan
    Gene 248:183-9. 2000
    ..This putative seven-transmembrane domain receptor of 469 amino acids was designated SALPR (Somatostatin- and Angiotensin- Like Peptide Receptor)...
  7. ncbi 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
    Changlu Liu
    Johnson and Johnson Pharmaceutical Research and Development, L L C, San Diego, CA 92121, USA
    Mol Pharmacol 67:231-40. 2005
    ..of relaxin/insulin family, is an agonist for leucine-rich repeat-containing G protein-coupled receptor (LGR)7, GPCR135, and GPCR142...
  8. ncbi Identification of relaxin-3/INSL7 as an endogenous ligand for the orphan G-protein-coupled receptor GPCR135
    Changlu Liu
    Johnson and Johnson Pharmaceutical Research and Development, L L C, San Diego, California 92121, USA
    J Biol Chem 278:50754-64. 2003
    b>GPCR135, publicly known as somatostatin- and angiotensin-like peptide receptor, is expressed in the central nervous system and its cognate ligand(s) has not been identified...
  9. ncbi Relaxin receptors--new drug targets for multiple disease states
    E T van der Westhuizen
    Department of Pharmacology, Monash University, Wellington Road, Clayton, Victoria 3800, Australia
    Curr Drug Targets 8:91-104. 2007
    ..The recent de-orphanisation of four receptors LGR7, LGR8, GPCR135 (SALPR) and GPCR142 (GPR100) that respond to and bind at least one of the three forms of relaxin identified to ..
  10. ncbi 'Relaxin' the stiffened heart and arteries: the therapeutic potential for relaxin in the treatment of cardiovascular disease
    Chrishan S Samuel
    Howard Florey Institute, University of Melbourne, Victoria 3010, Australia Department of Biochemistry and Molecular Biology, University of Melbourne, Victoria 3010, Australia
    Pharmacol Ther 112:529-52. 2006
    ..H3/relaxin-3 gene, and the elusive receptors for relaxin (Relaxin family peptide receptor; RXFP1) and relaxin-3 (RXFP3/RXFP4) have led to the re-classification of a distinct relaxin peptide/receptor family...
  11. ncbi Coevolution of the relaxin-like peptides and their receptors
    Tracey N Wilkinson
    Howard Florey Institute, The University of Melbourne, Victoria 3010, Australia
    Ann N Y Acad Sci 1041:534-9. 2005
    ..although it also interacts specifically with relaxin-3; LGR8 is the insulin-like factor 3 (INSL3) receptor; and GPCR135 or the somatostatin- and angiotensin-like peptide receptor (SALPR) and GPCR142 are both specific relaxin-3 ..
  12. doi Relaxin-3/RXFP3 system regulates alcohol-seeking
    Philip J Ryan
    The Florey Institute of Neuroscience and Mental Health, Department of Anatomy and Neuroscience, and School of Chemistry, The University of Melbourne, VIC 3010, Australia
    Proc Natl Acad Sci U S A 110:20789-94. 2013
    ..we demonstrated that central administration of peptide antagonists for relaxin family peptide 3 receptor (RXFP3), the cognate receptor for the highly conserved neuropeptide, relaxin-3, decreased self-administration of alcohol ..
  13. doi Relaxin polymorphisms associated with metabolic disturbance in patients treated with antipsychotics
    Janet Munro
    Optimal Medicine Ltd, Warwick Enterprise Park, Wellesbourne, Warwick, UK
    J Psychopharmacol 26:374-9. 2012
    ..We have investigated the role of ten polymorphisms in these genes (RLN3 rs12327666, rs1982632, and rs7249702, RLN3R1 rs42868, rs6861957, rs7702361, and rs35399, and RLN3R2 rs11264422, rs1018730 and rs12124383) in the occurrence of ..
  14. doi Site-specific DOTA/europium-labeling of recombinant human relaxin-3 for receptor-ligand interaction studies
    Wei Jie Zhang
    Institute of Protein Research, College of Life Sciences and Technology, Tongji University, Shanghai 200092, China
    Amino Acids 43:983-92. 2012
    ..of stress responses, food intake, and reproduction by activation of its cognate G-protein-coupled receptor RXFP3. It also binds and activates the relaxin family peptide receptors RXFP1 and RXFP4 in vitro...
  15. doi Minimization of human relaxin-3 leading to high-affinity analogues with increased selectivity for relaxin-family peptide 3 receptor (RXFP3) over RXFP1
    Fazel Shabanpoor
    Florey Neuroscience Institutes, The University of Melbourne, Victoria 3010, Australia
    J Med Chem 55:1671-81. 2012
    ..to develop analogues of human relaxin-3 (H3 relaxin) that can selectively bind and activate its receptor, RXFP3. We developed a high-affinity selective agonist (analogue 2) by removal of the intra-A chain disulfide bond and ..
  16. doi Design, recombinant expression and convenient A-chain N-terminal europium-labelling of a fully active human relaxin-3 analogue
    Wei Jie Zhang
    Institute of Protein Research, College of Life Sciences and Technology, Tongji University, Shanghai, China
    FEBS J 279:1505-12. 2012
    ..of food intake, in the stress response and in reproduction by activating the G-protein-coupled receptor, RXFP3. In a previous study, we prepared 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)/Eu(3+)-labelled ..
  17. doi Relaxin family peptides and their receptors
    R A D Bathgate
    Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences and Department of Pharmacology, Monash University, Victoria, Australia
    Physiol Rev 93:405-80. 2013
    ..Relaxin-3 and INSL5 are the cognate ligands for RXFP3 and RXFP4 that are closely related to small peptide receptors that when activated inhibit cAMP production and ..
  18. doi A convenient method for europium-labeling of a recombinant chimeric relaxin family peptide R3/I5 for receptor-binding assays
    Wei Jie Zhang
    Institute of Protein Research, College of Life Sciences and Technology, Tongji University, Shanghai, China
    J Pept Sci 19:350-4. 2013
    ..peptide R3/I5, containing the B-chain of relaxin-3 and the A-chain of INSL5, is a selective agonist for both RXFP3 and RXFP4...
  19. doi Acute antipsychotic treatments induce distinct c-Fos expression patterns in appetite-related neuronal structures of the rat brain
    Ramamoorthy Rajkumar
    Department of Pharmacology, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, Singapore 117597, Singapore
    Brain Res 1508:34-43. 2013
    ..ArcN, PVN, and PVA receive RLN3 immunoreactive fibers from the NI and express relaxin family peptide type 3 (RXFP3) receptor...
  20. doi Chemical synthesis and orexigenic activity of rat/mouse relaxin-3
    Mohammed Akhter Hossain
    Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Victoria, 3010, Australia
    Amino Acids 44:1529-36. 2013
    ..Its actions are mediated via its cognate G protein-coupled receptor, RXFP3, which is found in abundant numbers in the brain...
  21. pmc Elucidation of relaxin-3 binding interactions in the extracellular loops of RXFP3
    Ross A D Bathgate
    Florey Institute of Neuroscience and Mental Health, University of Melbourne Parkville, Vic, Australia Department of Biochemistry and Molecular Biology, University of Melbourne Parkville, Vic, Australia
    Front Endocrinol (Lausanne) 4:13. 2013
    ..a highly conserved neuropeptide in vertebrate species and binds to the Class A G protein-coupled receptor (GPCR) RXFP3. Relaxin-3 is involved in a wide range of behaviors, including feeding, stress responses, arousal, and cognitive ..
  22. doi Relaxin-3 innervation of the intergeniculate leaflet of the rat thalamus - neuronal tract-tracing and in vitro electrophysiological studies
    Anna Blasiak
    Department of Neurophysiology and Chronobiology, Jagiellonian University, Gronostajowa 9, 30 387, Krakow, Poland
    Eur J Neurosci 37:1284-94. 2013
    ..The relaxin-3 and relaxin family peptide receptor 3 (RXFP3) system has emerged as a putative ascending arousal network with putative involvement in ..
  23. doi Increased feeding and body weight gain in rats after acute and chronic activation of RXFP3 by relaxin-3 and receptor-selective peptides: functional and therapeutic implications
    Despina E Ganella
    Florey Neuroscience Institutes, The University of Melbourne, Victoria, Australia
    Behav Pharmacol 23:516-25. 2012
    ..peptide (RXFP) receptors, studies with relaxin-3 analogues selective for the native relaxin-3 receptor, RXFP3, confirmed that acute and chronic activation of RXFP3 increased feeding and weight gain, and produced changes in ..
  24. doi Relaxin: new pathophysiological aspects and pharmacological perspectives for an old protein
    Valeria Cernaro
    Department of Internal Medicine, University of Messina, Via Consolare Valeria, 1, 98100, Italy
    Med Res Rev 34:77-105. 2014
    ..with different types of receptors, classified as relaxin family peptide (RXFP) receptors (RXFP1, RXFP2, RXFP3, RXFP4)...
  25. doi Central relaxin-3 receptor (RXFP3) activation decreases anxiety- and depressive-like behaviours in the rat
    Philip J Ryan
    The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Victoria, Australia
    Behav Brain Res 244:142-51. 2013
    ..postulated to modulate affective behaviour, based on high densities of the relaxin-3 G-protein coupled receptor (RXFP3) in brain areas involved in stress and mood/anxiety, including the central amygdala, bed nucleus of the stria ..
  26. doi Distribution of relaxin-3 mRNA and immunoreactivity and RXFP3-binding sites in the brain of the macaque, Macaca fascicularis
    Sherie Ma
    Howard Florey Institute, University of Melbourne, Victoria, Australia
    Ann N Y Acad Sci 1160:256-8. 2009
    This study examined the presence and distribution of relaxin-3 (RLN3) and its receptor, RXFP3, throughout the brain of Macaca fascicularis...
  27. ncbi Central relaxin-3 administration causes hyperphagia in male Wistar rats
    B M C McGowan
    Endocrine Unit, Imperial College School of Medicine, Hammersmith Hospital, London W12 ONN, United Kingdom
    Endocrinology 146:3295-300. 2005
    ..Relaxin-3 binds with high affinity to the LGR7 receptor and to the previously orphan G protein-coupled receptor GPCR135. GPCR135 mRNA is expressed predominantly in the central nervous system, particularly in the paraventricular ..
  28. doi Verification of a relaxin-3 knockout/LacZ reporter mouse as a model of relaxin-3 deficiency
    Craig M Smith
    Howard Florey Institute, University of Melbourne, Victoria, Australia
    Ann N Y Acad Sci 1160:259-60. 2009
    ..Anatomical studies have yielded important information on the distribution of relaxin-3 and its cognate receptor (RXFP3) within the brain, while functional studies have implicated relaxin-3 as a modulator of feeding and stress ..
  29. doi Localization of relaxin-3 in brain of Macaca fascicularis: identification of a nucleus incertus in primate
    Sherie Ma
    Florey Neuroscience Institutes, The University of Melbourne, Victoria 3010, Australia
    J Comp Neurol 517:856-72. 2009
    ..and pharmacological studies suggest that RLN3 is the cognate ligand for the relaxin family peptide-3 receptor (RXFP3). The distribution of RLN3/RXFP3 networks has been determined in rat and mouse brain, but not in higher species...
  30. doi Relaxin-3 and its role in neuroendocrine function
    Barbara M C McGowan
    Department of Investigative Medicine, Division of Investigative Science, Imperial College London, Hammersmith Hospital, London, UK
    Ann N Y Acad Sci 1160:250-5. 2009
    ..incertus of the brainstem, which has projections to the hypothalamus and is thought to act in the brain via the RXFP3 receptor, although the RXFP1 receptor may also play a role...
  31. doi Metabolic and neuroendocrine responses to RXFP3 modulation in the central nervous system
    Steven W Sutton
    Johnson and Johnson Pharmaceutical Research and Development, LLC, San Diego, California 92121, USA
    Ann N Y Acad Sci 1160:242-9. 2009
    ..the rodent nucleus incertus (NI), project widely into a large number of areas expressing the relaxin-3 receptor (RXFP3), and these data suggest relaxin-3/RXFP3 signaling modulates sensory, emotional, and neuroendocrine processing...
  32. doi Relaxin family peptides and receptors in mammalian brain
    Andrew L Gundlach
    Howard Florey Institute, Florey Neuroscience Institutes, University of Melbourne, Victoria, Australia
    Ann N Y Acad Sci 1160:226-35. 2009
    ..Here we review progress in mapping RXFP1, RXFP2, and RXFP3 (mRNAs and proteins) and their respective ligands and discuss some of the putative functions for these peptides ..
  33. doi Addition of a carboxy-terminal green fluorescent protein does not alter the binding and signaling properties of relaxin family Peptide receptor 3
    Emma T Van der Westhuizen
    Department of Pharmacology, Monash Institute of Pharmaceutical Sciences, Monash University, Clayton, Victoria 3800, Australia
    Ann N Y Acad Sci 1160:105-7. 2009
    The relaxin family peptide receptor 3 (RXFP3) is the cognate receptor for the neuropeptide relaxin-3...
  34. doi Probing the functional domains of relaxin-3 and the creation of a selective antagonist for RXFP3/GPCR135 over relaxin receptor RXFP1/LGR7
    Changlu Liu
    Johnson and Johnson Pharmaceutical Research and Development, LLC, San Diego, California 92121, USA
    Ann N Y Acad Sci 1160:31-7. 2009
    Both relaxin-3 and its receptor (RXFP3, also known as GPCR135) are predominantly expressed in brain regions known to play important roles in processing sensory signals...
  35. doi Membrane receptors: structure and function of the relaxin family peptide receptors
    Roy C K Kong
    Florey Neuroscience Institutes, University of Melbourne, Victoria 3010, Australia
    Mol Cell Endocrinol 320:1-15. 2010
    ..and INSL5 interact with another class of type I GPCRs which lack a large ectodomain, the peptide receptors GPCR135 and GPCR142, respectively...
  36. doi H2 relaxin is a biased ligand relative to H3 relaxin at the relaxin family peptide receptor 3 (RXFP3)
    Emma T Van der Westhuizen
    Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Parkville, Victoria, Australia
    Mol Pharmacol 77:759-72. 2010
    Relaxin family peptide 3 receptors (RXFP3) are activated by H3-relaxin to inhibit forskolin-stimulated cAMP accumulation and stimulate extracellular signal-regulated kinase (ERK) 1/2 phosphorylation...
  37. doi Relaxin-3 systems in the brain--the first 10 years
    Craig M Smith
    Florey Neuroscience Institutes, The University of Melbourne, Victoria, Australia
    J Chem Neuroanat 42:262-75. 2011
    ..of the peptide, including the identification of its cognate receptor (a type 1 G-protein coupled receptor, GPCR135 or RXFP3), an understanding of its structure-activity and associated cellular signalling, and the elucidation of ..
  38. doi Nucleus incertus--an emerging modulatory role in arousal, stress and memory
    Philip J Ryan
    Howard Florey Institute and Florey Neuroscience Institutes, The University of Melbourne, Victoria 3010, Australia
    Neurosci Biobehav Rev 35:1326-41. 2011
    ..of structurally-related, chimeric peptides that selectively activate or inhibit the relaxin-3 receptor, RXFP3, is facilitating studies of relaxin-3/RXFP3 networks and associated GABA and CRF systems...
  39. ncbi The roles of the A- and B-chains of human relaxin-2 and -3 on their biological activity
    Mohammed Akhter Hossain
    Florey Neuroscience Institutes, University of Melbourne, Victoria 3010, Australia
    Curr Protein Pept Sci 11:719-24. 2010
    ..The native receptor for H3 relaxin is the unrelated receptor, RXFP3; however, it also has high affinity for another related receptor, RXFP4...
  40. doi H3 relaxin demonstrates antifibrotic properties via the RXFP1 receptor
    Mohammed Akhter Hossain
    Howard Florey Institute, School of Chemistry, and Department of Biochemistry and Molecular Biology, The University of Melbourne, Parkville, Victoria 3010, Australia
    Biochemistry 50:1368-75. 2011
    ..While its effects as a neuromodulator are being increasingly studied through its primary receptor, RXFP3, its actions via other RXFPs are poorly understood...
  41. doi Design, synthesis, and characterization of a single-chain peptide antagonist for the relaxin-3 receptor RXFP3
    Linda M Haugaard-Kedström
    School of Natural Sciences, Linnaeus University, SE 391 82 Kalmar, Sweden
    J Am Chem Soc 133:4965-74. 2011
    ..that is the ancestral member of the relaxin peptide family and, together with its G protein-coupled receptor RXFP3, is highly expressed in the brain...
  42. doi Relaxin-3/insulin-like peptide 7, a neuropeptide involved in the stress response and food intake
    Masaki Tanaka
    Department of Basic Geriatrics, Kyoto Prefectural University of Medicine, Kamikyo ku, Kyoto, Japan
    FEBS J 277:4990-7. 2010
    ..On the other hand, relaxin-3-expressing nerve fibers and the relaxin-3 receptors, RXFP3 and RXFP1, are widely distributed in the forebrain, with the hypothalamus being one of the most densely-innervated ..
  43. doi Distribution of relaxin-3 and RXFP3 within arousal, stress, affective, and cognitive circuits of mouse brain
    Craig M Smith
    Florey Neuroscience Institutes, The University of Melbourne, Victoria 3010, Australia
    J Comp Neurol 518:4016-45. 2010
    Relaxin-3 (RLN3) and its native receptor, relaxin family peptide 3 receptor (RXFP3), constitute a newly identified neuropeptide system enriched in mammalian brain...
  44. doi A simple approach for the preparation of mature human relaxin-3
    Xiao Luo
    Institute of Protein Research, Tongji University, 1239 Siping Road, Shanghai 200092, China
    Peptides 31:2083-8. 2010
    ..The recombinant mature relaxin-3 was fully active in both RXFP3 binding and activation assays...
  45. pmc Promoter hypermethylation of CIDEA, HAAO and RXFP3 associated with microsatellite instability in endometrial carcinomas
    Yi Wen Huang
    Human Cancer Genetics Program, Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA
    Gynecol Oncol 117:239-47. 2010
    ..The purpose of this study is to identify novel hypermethylated loci associated with clinicopathologic variables in endometrioid endometrial carcinomas...
  46. doi Structural properties of relaxin chimeras
    Linda M Haugaard-Jönsson
    School of Pure and Applied Natural Sciences, University of Kalmar, Kalmar, Sweden
    Ann N Y Acad Sci 1160:27-30. 2009
    Relaxin-3 interacts with high potency with three relaxin family peptide receptors (RXFP1, RXFP3, and RXFP4)...
  47. doi De novo design and synthesis of cyclic and linear peptides to mimic the binding cassette of human relaxin
    Mohammed Akhter Hossain
    Howard Florey Institute, University of Melbourne, Parkville, Victoria, Australia
    Ann N Y Acad Sci 1160:16-9. 2009
    ..None showed any binding affinity for RXFP1, RXFP2, or RXFP3, indicating that the key residues were either incorrectly oriented or that additional residues are required for ..
  48. doi Structure and activity in the relaxin family of peptides
    Geoffrey W Tregear
    Department of Biochemistry and Molecular Biology, Howard Florey Institute, University of Melbourne, Parkville, Victoria, Australia
    Ann N Y Acad Sci 1160:5-10. 2009
    ..on structure and function relates to the relaxin-RXFP1, insulin-like peptide 3 (INSL3)-RXFP2, and relaxin-3-RXFP3 systems, with information accumulating not only on the critical ligand structures but also the domains and ..
  49. ncbi Relaxin-a pleiotropic hormone and its emerging role for experimental and clinical therapeutics
    Thomas Dschietzig
    Medizinische Klinik m S Kardiologie und Angiologie, Charite Universitatsmedizin Berlin, Campus Mitte, Schumannstr 20 21, 10117 Berlin, Germany
    Pharmacol Ther 112:38-56. 2006
    ..current state of insight into this rapidly evolving field, which has further been expanded by the discovery of GPCR135 and GPCR142 as receptors for Rlx-3...
  50. ncbi Solution structure and novel insights into the determinants of the receptor specificity of human relaxin-3
    K Johan Rosengren
    Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland 4072, Australia
    J Biol Chem 281:5845-51. 2006
    ..This structural feature is likely important for the activation of its endogenous receptor, GPCR135.
  51. ncbi Evolution of the signaling system in relaxin-family peptides
    Sheau Yu Teddy Hsu
    Division of Reproductive Biology, Department of Obstetrics and Gynecology, Stanford University School of Medicine, Stanford, CA 94305 5317, USA
    Ann N Y Acad Sci 1041:520-9. 2005
    ..In addition, INSL7/relaxin3 signals through two orphan GPCRs, GPCR135 and GPCR142, whereas INSL5 is a select ligand for GPCR142...
  52. ncbi Responses of GPCR135 to human gene 3 (H3) relaxin in CHO-K1 cells determined by microphysiometry
    Emma T Van der Westhuizen
    Department of Pharmacology, Monash University, Clayton 3168, Australia
    Ann N Y Acad Sci 1041:332-7. 2005
    ..porcine relaxin, and human INSL3 in the cytosensor microphysiometer, using CHO-K1 cells stably expressing human GPCR135. CHO-K1 cells stably expressing GPCR135 were generated by the serial dilution method and receptor properties were ..
  53. ncbi Insulin-relaxin family peptide signaling and receptors in mouse brain membranes and neuronal cells
    Stefanie Ortinau
    Howard Florey Institute of Experimental Physiology and Medicine, The University of Melbourne, Victoria 3010, Australia
    Ann N Y Acad Sci 1041:211-5. 2005
    Several orphan G-protein-coupled receptors (GPCRs), LGR7 and LGR8, GPCR135 and GPCR142, were recently identified as putative, native receptors for different relaxin-family peptides, and their cell signaling mechanisms were elucidated in ..
  54. ncbi Localization of LGR7 (relaxin receptor) mRNA and protein in rat forebrain: correlation with relaxin binding site distribution
    Tanya C D Burazin
    Howard Florey Institute of Experimental Physiology and Medicine, The University of Melbourne, Victoria 3010, Australia
    Ann N Y Acad Sci 1041:205-10. 2005
    ..relaxin and relaxin-3, and molecular studies have identified former-orphan, G-protein-coupled receptors LGR7 and GPCR135 as their native receptors...
  55. ncbi Receptors for relaxin family peptides
    Ross A Bathgate
    Howard Florey Institute of Experimental Physiology and Medicine, University of Melbourne, Victoria 3010, Australia
    Ann N Y Acad Sci 1041:61-76. 2005
    ..receptors with LGR7 (RXFP1) and LGR8 (RXFP2) being type C leucine-rich repeat-containing receptors, whereas GPCR135 (RXFP3) and GPCR142 (RXFP4) resemble receptors that respond to small peptides such as somatostatin and ..
  56. ncbi Recent progress in relaxin-3-related research
    Changlu Liu
    Johnson and Johnson Pharmaceutical Research and Development, LLC, San Diego, CA 92121
    Ann N Y Acad Sci 1041:47-60. 2005
    ..We recently identified R3 as a ligand for two orphan G-protein coupled receptors, GPCR135 and GPCR142...
  57. ncbi INSL5 is a high affinity specific agonist for GPCR142 (GPR100)
    Changlu Liu
    Johnson and Johnson Pharmaceutical Research and Development, San Diego, California 92121, USA
    J Biol Chem 280:292-300. 2005
    ..However, unlike relaxin-3, which is also a potent agonist for GPCR135 and LGR7, INSL5 does not activate either GPCR135 or LGR7...
  58. ncbi Pharmacological characterization of relaxin-3/INSL7 receptors GPCR135 and GPCR142 from different mammalian species
    Jingcai Chen
    Johnson and Johnson Pharmaceutical Research and Development, L L C, 3210 Merryfield Row, San Diego, CA 92121, USA
    J Pharmacol Exp Ther 312:83-95. 2005
    Relaxin-3 has recently been identified as a ligand for two structurally related G-protein-coupled receptors, human GPCR135 and GPCR142...
  59. ncbi Identification of a mouse orthologue of the G-protein-coupled receptor SALPR and its expression in adult mouse brain and during development
    Katrin Boels
    Zentrum für Molekulare Neurobiologie, Universitat Hamburg, Martinistrasse 52, 20246 Hamburg, Germany
    Brain Res Dev Brain Res 152:265-8. 2004
    The mouse orthologue of somatostatin and angiotensin-like peptide receptor (SALPR) was amplified from cDNA of the hippocampal cell line HT22...
  60. pmc Identification and characterisation of GPR100 as a novel human G-protein-coupled bradykinin receptor
    Katrin Boels
    Zentrum für Molekulare Neurobiologie, Universitat Hamburg, Martinistrasse 52, Hamburg 20246, Germany
    Br J Pharmacol 140:932-8. 2003
    ....
  61. ncbi 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
    Steven W Sutton
    Johnson and Johnson Pharmaceutical Research and Development, LLC, San Diego, CA 92121, USA
    Neuroendocrinology 82:139-50. 2005
    ..We have recently described a chimeric R3/I5 peptide that selectively activates GPCR135 and GPCR142, but lacks affinity for LGR7...
  62. ncbi Relaxin-3 in GABA projection neurons of nucleus incertus suggests widespread influence on forebrain circuits via G-protein-coupled receptor-135 in the rat
    S Ma
    Howard Florey Institute, The University of Melbourne, Melbourne, Victoria 3010, Australia
    Neuroscience 144:165-90. 2007
    ..studies have demonstrated that RLX3 is a high affinity, selective ligand for G-protein-coupled receptor-135 (GPCR135, now classified as relaxin family peptide-3 receptor; RXFP3)...
  63. ncbi Hypothalamic mapping of orexigenic action and Fos-like immunoreactivity following relaxin-3 administration in male Wistar rats
    B M McGowan
    Department of Metabolic Medicine, Imperial College London, 6th Floor Commonwealth Bldg, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK
    Am J Physiol Endocrinol Metab 292:E913-9. 2007
    ..family peptide receptor 1, which also binds relaxin-1, and a previously orphaned G protein-coupled receptor, RXFP3. These receptors are extensively expressed in the hypothalamus...
  64. doi Solid phase synthesis and structural analysis of novel A-chain dicarba analogs of human relaxin-3 (INSL7) that exhibit full biological activity
    Mohammed Akhter Hossain
    Howard Florey Institute, University of Melbourne, Victoria, 3010, Australia
    Org Biomol Chem 7:1547-53. 2009
    ..Both peptides demonstrated binding affinities that were equivalent to native H3 relaxin on RXFP1 and RXFP3 expressing cells...
  65. doi The structural and functional role of the B-chain C-terminal arginine in the relaxin-3 peptide antagonist, R3(BDelta23-27)R/I5
    Mohammed Akhter Hossain
    Howard Florey Institute, University of Melbourne, Melbourne, Victoria 3010, Australia
    Chem Biol Drug Des 73:46-52. 2009
    ..It is highly expressed in the brain and is the endogenous ligand for the receptor RXFP3. As relaxin-3 also interacts with the relaxin receptor RXFP1, selective agonists and antagonists are crucial for ..
  66. doi Relaxin-3 and RXFP3 expression, and steroidogenic actions in the ovary of teleost fish
    Brian C Wilson
    Department of Biology, Acadia University, Wolfville, Nova Scotia, Canada
    Comp Biochem Physiol A Mol Integr Physiol 153:69-74. 2009
    ..Ovarian expression of relaxin-3a, d and f genes, and the relaxin-3 receptor gene Rxfp3, was studied in Danio rerio using RT-PCR...
  67. doi Relaxin family peptide receptors--from orphans to therapeutic targets
    Emma T Van der Westhuizen
    Department of Pharmacology, Monash University, Clayton, 3800 Vic, Australia
    Drug Discov Today 13:640-51. 2008
    ..are the cognate ligands for 4 G-protein-coupled relaxin family peptide receptors (RXFPs; formerly LGR7, LGR8, GPCR135, GPCR142)...
  68. doi Identification of the domains in RXFP4 (GPCR142) responsible for the high affinity binding and agonistic activity of INSL5 at RXFP4 compared to RXFP3 (GPCR135)
    Jessica Zhu
    Johnson and Johnson Pharmaceutical Research and Development, L L C, 3210 Merryfield Row, San Diego, CA 92121, USA
    Eur J Pharmacol 590:43-52. 2008
    Relaxin-3 is a potent agonist for both G-protein coupled receptors (GPCR) RXFP3 (also known as GPCR135) and RXFP4 (also known as GPCR142) while insulin-like peptides 5 (INSL5) is a selective RXFP4 agonist...
  69. pmc Structure of the R3/I5 chimeric relaxin peptide, a selective GPCR135 and GPCR142 agonist
    Linda M Haugaard-Jönsson
    School of Pure and Applied Natural Sciences, University of Kalmar, SE 391 82 Kalmar, Sweden
    J Biol Chem 283:23811-8. 2008
    ..relaxin family ancestor, relaxin-3, which is an agonist for three of the four currently known relaxin receptors: GPCR135, GPCR142, and LGR7...
  70. pmc Synthesis, conformation, and activity of human insulin-like peptide 5 (INSL5)
    Mohammed Akhter Hossain
    Howard Florey Institute, University of Melbourne, Victoria 3010, Australia
    Chembiochem 9:1816-22. 2008
    ..In contrast, it had no activity on the human RXFP3 receptor...
  71. pmc Relaxin-3 stimulates the hypothalamic-pituitary-gonadal axis
    B M McGowan
    Dept of Investigative Medicine, Division of Investigative Science, Imperial College London, Hammersmith Campus, Du Cane Road, London, UK
    Am J Physiol Endocrinol Metab 295:E278-86. 2008
    ..Relaxin-3 is thought to act in the brain via the RXFP3 receptor, although the RXFP1 receptor may also play a role...
  72. doi The A-chain of human relaxin family peptides has distinct roles in the binding and activation of the different relaxin family peptide receptors
    Mohammed Akhter Hossain
    Howard Florey Institute and Department of Biochemistry and Molecular Biology, University of Melbourne, Victoria, Australia
    J Biol Chem 283:17287-97. 2008
    ..classes of G-protein-coupled receptors (GPCRs), leucine-rich repeat-containing GPCRs LGR7 and LGR8 together with GPCR135 and GPCR142, now referred to as the relaxin family peptide (RXFP) receptors 1-4, respectively...
  73. doi Relaxin-3, INSL5, and their receptors
    Changlu Liu
    Johnson and Johnson Pharmaceutical Research and Development, LLC, San Diego, California 92121, USA
    Results Probl Cell Differ 46:213-37. 2008
    ..We recently identified R3 as a ligand for two orphan G-protein coupled receptors, GPCR135 (aka SALPR) and GPCR142 (aka GPR100), which are class-A GPCRs and typical neuropeptide receptors...
  74. ncbi Relaxin-family peptide and receptor systems in brain: insights from recent anatomical and functional studies
    Sherie Ma
    Howard Florey Institute, The University of Melbourne, Victoria 3010, Australia
    Adv Exp Med Biol 612:119-37. 2007
    ..the identification of a new relaxin family peptide, known as relaxin 3 and its type I G-protein-coupled receptor--GPCR135. Relaxin 3 was subsequently found to be highly conserved throughout evolution and to be the likely ancestral gene/..
  75. ncbi The evolution of the relaxin peptide family and their receptors
    Tracey N Wilkinson
    Howard Florey Institute, University of Melbourne, Victoria 3010, Australia
    Adv Exp Med Biol 612:1-13. 2007
    ..repeat containing G protein-coupled receptors (LGR), LGR7 and LGR8 respectively; and the two relaxin-3 receptors, GPCR135 and GPCR142...
  76. ncbi R3(BDelta23 27)R/I5 chimeric peptide, a selective antagonist for GPCR135 and GPCR142 over relaxin receptor LGR7: in vitro and in vivo characterization
    Chester Kuei
    Johnson and Johnson Pharmaceutical Research and Development, LLC, San Diego, California 92121, USA
    J Biol Chem 282:25425-35. 2007
    Both relaxin-3 and its receptor (GPCR135) are expressed predominantly in brain regions known to play important roles in processing sensory signals...
  77. ncbi The relaxin family peptide receptor 3 activates extracellular signal-regulated kinase 1/2 through a protein kinase C-dependent mechanism
    Emma T Van der Westhuizen
    Department of Pharmacology, PO Box 13E, Monash University, Clayton, Victoria, Australia
    Mol Pharmacol 71:1618-29. 2007
    ..The relaxin family peptide receptor 3 (RXFP3, formerly GPCR135 or SALPR) was characterized as the receptor for H3 relaxin, functionally ..
  78. pmc Relaxin family peptide receptors--former orphans reunite with their parent ligands to activate multiple signalling pathways
    M L Halls
    Department of Pharmacology, Monash University, Clayton, Victoria, Australia
    Br J Pharmacol 150:677-91. 2007
    ..The leucine-rich repeat containing RXFP1 and RXFP2 and the small peptide-like RXFP3 and RXFP4 are the physiological targets for relaxin, insulin-like (INSL) peptide 3, relaxin-3 and INSL5, ..
  79. ncbi Identification of relaxin-3/INSL7 as a ligand for GPCR142
    Changlu Liu
    Johnson and Johnson Pharmaceutical Research and Development, L L C, San Diego, California 92121, USA
    J Biol Chem 278:50765-70. 2003
    ..the insulin-like peptide relaxin-3 (aka INSL7) as the endogenous ligand for an orphan G-protein-coupled receptor, GPCR135 (aka somatostatin- and angiotensin-like peptide receptor)...

Research Grants9

  1. PHYSIOLOGY OF RELAXIN-INSULIN-LIKE FACTORS
    Sheau Yu Hsu; Fiscal Year: 2002
    ..Additionally, knowledge gathered from the proposed experiments would help the diagnosis and treatment of diseases associated with the dysfunction of these novel relaxin/insulin-like factors. ..
  2. Identification of Relaxin Receptor Antagonists
    Sheau Yu Hsu; Fiscal Year: 2005
    ..These antagonists could be used to block relaxin action during preterm labor as well as provide a tool for further research on the role of LGR7 and LGR8 in reproductive tract physiology. ..
  3. Role of RAMPs in Intermedin Signaling
    Sheau Yu Hsu; Fiscal Year: 2009
    ....
  4. Role of RAMPs in Intermedin Signaling
    Sheau Yu Teddy Hsu; Fiscal Year: 2010
    ....