| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
IUPHAR Nomenclature Report |
Howard Florey Institute, University of Melbourne, Melbourne, Victoria, Australia (R.A.B.); School of Molecular and Biomedical Science, The University of Adelaide, South Australia, Australia (R.I.); Department of Biological Sciences, Colorado State University, Fort Collins, Colorado (B.M.S.); Department of Molecular and Integrative Physiology and College of Medicine, University of Illinois at Urbana-Champaign, Urbana, Illinois (O.D.S.); Department of Pharmacology, Monash University, Clayton, Victoria, Australia (R.J.S.)
Abstract
Abstract I. Brief Historical Background of Relaxin Family Peptides and Their Receptors II. Receptor Distribution and Function A. Reproductive Tissues B. Brain C. Cardiovascular and Renal Systems D. Other Sites of Action of Relaxin Family Peptides E. Roles of Relaxin Family Peptides Determined from Studies in Receptor Knockout Mice III. Structure of Relaxin Family Peptides A. Structural Features of Relaxin B. Structural Features of Other Relaxin Family Peptides IV. Structure-Activity Relationships A. Relaxin B. INSL3 V. Binding of Relaxin and Relaxin Family Peptides A. Relaxin Binding B. Binding of Other Relaxin Family Peptides VI. Relaxin Family Peptide Receptors A. RXFP1 and RXFP2 B. RXFP3 and RXFP4 VII. Functional Domains of Receptors for Relaxin Family Peptides A. General Features of Leucine-Rich Repeat-Containing Receptors B. Functional Domains of RXFP1 and RXFP2 (LGR7 and LGR8) C. Functional Domains of RXFP3 and RXFP4 (GPCR135 and GPCR142) VIII. Signaling Pathways Activated by Relaxin Family Peptides A. Signaling in Response to Relaxin B. Signaling in Response to Other Relaxin Family Peptides IX. Regulation of Relaxin Family Peptide Receptors X. Nomenclature Issues for Relaxin Family Peptides and Their Receptors
Although the hormone relaxin was discovered 80 years ago, only in the past 5 years have the receptors for relaxin and three other receptors that respond to related peptides been identified with all four receptors being G-protein-coupled receptors. In this review it is suggested that 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). RXFP1 and RXFP2 are leucine-rich repeat-containing G-protein-coupled receptors with complex binding characteristics involving both the large ectodomain and the transmembrane loops. RXFP1 activates adenylate cyclase, protein kinase A, protein kinase C, phosphatidylinositol 3-kinase, and extracellular signaling regulated kinase (Erk1/2) and also interacts with nitric oxide signaling. RXFP2 activates adenylate cyclase in recombinant systems, but physiological responses are sensitive to pertussis toxin. RXFP3 and RXFP4 resemble more conventional peptide liganded receptors and both inhibit adenylate cyclase, and in addition RXFP3 activates Erk1/2 signaling. Physiological studies and examination of the phenotypes of transgenic mice have established that relaxin has roles as a reproductive hormone involved in uterine relaxation (some species), reproductive tissue growth, and collagen remodeling but also in the cardiovascular and renal systems and in the brain. The connective tissue remodeling properties of relaxin acting at RXFP1 receptors have potential for the development of agents effective for the treatment of cardiac and renal fibrosis, asthma, and scleroderma and for orthodontic remodelling. Agents acting at RXFP2 receptors may be useful for the treatment of cryptorchidism and infertility, whereas antagonists may be used as contraceptives. The brain distribution of RXFP3 receptors suggests that actions at these receptors have the potential for the development of antianxiety and antiobesity drugs.
This article has been cited by other articles:
|
|
 |
|
  R. Ivell and R. Anand-Ivell Biology of insulin-like factor 3 in human reproduction Hum. Reprod. Update, July 1, 2009; 15(4): 463 - 476. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Kern and G. D. Bryant-Greenwood Characterization of Relaxin Receptor (RXFP1) Desensitization and Internalization in Primary Human Decidual Cells and RXFP1-Transfected HEK293 Cells Endocrinology, May 1, 2009; 150(5): 2419 - 2428. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Mookerjee, T. D. Hewitson, M. L. Halls, R. J. Summers, M. L. Mathai, R. A. D. Bathgate, G. W. Tregear, and C. S. Samuel Relaxin inhibits renal myofibroblast differentiation via RXFP1, the nitric oxide pathway, and Smad2 FASEB J, April 1, 2009; 23(4): 1219 - 1229. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. S. Samuel, S. G. Royce, B. Chen, H. Cao, J. A. Gossen, G. W. Tregear, and M. L. K. Tang Relaxin Family Peptide Receptor-1 Protects against Airway Fibrosis during Homeostasis But Not against Fibrosis Associated with Chronic Allergic Airways Disease Endocrinology, March 1, 2009; 150(3): 1495 - 1502. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Heng, R. Ivell, P. Wagaarachchi, and R. Anand-Ivell Relaxin signalling in primary cultures of human myometrial cells Mol. Hum. Reprod., October 1, 2008; 14(10): 603 - 611. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Hossain, K. J. Rosengren, L. M. Haugaard-Jonsson, S. Zhang, S. Layfield, T. Ferraro, N. L. Daly, G. W. Tregear, J. D. Wade, and R. A. D. Bathgate 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., June 20, 2008; 283(25): 17287 - 17297. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Yao, A. I. Agoulnik, P. S. Cooke, D. D. Meling, and O. D. Sherwood Relaxin Acts on Stromal Cells to Promote Epithelial and Stromal Proliferation and Inhibit Apoptosis in the Mouse Cervix and Vagina Endocrinology, May 1, 2008; 149(5): 2072 - 2079. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Yan, J. Chen, A. A Wiley, B. D Crean-Harris, F. F Bartol, and C. A Bagnell Relaxin (RLX) and estrogen affect estrogen receptor {alpha}, vascular endothelial growth factor, and RLX receptor expression in the neonatal porcine uterus and cervix Reproduction, May 1, 2008; 135(5): 705 - 712. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Anand-Ivell, R. Ivell, D. Driscoll, and J. Manson Insulin-like factor 3 levels in amniotic fluid of human male fetuses Hum. Reprod., May 1, 2008; 23(5): 1180 - 1186. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Nuti, E. Marinari, E. Erdei, M. El-Hamshari, M. G. Echavarria, E. Ars, G. Balercia, M. Merksz, C. Giachini, K. Z. M. Shaeer, et al. The Leucine-Rich Repeat-Containing G Protein-Coupled Receptor 8 Gene T222P Mutation Does Not Cause Cryptorchidism J. Clin. Endocrinol. Metab., March 1, 2008; 93(3): 1072 - 1076. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Kern, D. Hubbard, A. Amano, and G. D. Bryant-Greenwood Cloning, Expression, and Functional Characterization of Relaxin Receptor (Leucine-Rich Repeat-Containing G Protein-Coupled Receptor 7) Splice Variants from Human Fetal Membranes Endocrinology, March 1, 2008; 149(3): 1277 - 1294. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Q. Xu, E. D. Lekgabe, X.-M. Gao, Z. Ming, G. W. Tregear, A. M. Dart, R. A. D. Bathgate, C. S. Samuel, and X.-J. Du Endogenous Relaxin Does Not Affect Chronic Pressure Overload-Induced Cardiac Hypertrophy and Fibrosis Endocrinology, February 1, 2008; 149(2): 476 - 482. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Feng, N. V Bogatcheva, A. Truong, B. Korchin, C. E Bishop, T. Klonisch, I. U Agoulnik, and A. I Agoulnik Developmental Expression and Gene Regulation of Insulin-like 3 Receptor RXFP2 in Mouse Male Reproductive Organs Biol Reprod, October 1, 2007; 77(4): 671 - 680. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. M. El-Shewy, M.-H. Lee, L. M. Obeid, A. A. Jaffa, and L. M. Luttrell The Insulin-like Growth Factor Type 1 and Insulin-like Growth Factor Type 2/Mannose-6-phosphate Receptors Independently Regulate ERK1/2 Activity in HEK293 Cells J. Biol. Chem., September 7, 2007; 282(36): 26150 - 26157. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. J. Scott, T. N. Wilkinson, S. Zhang, T. Ferraro, J. D. Wade, G. W. Tregear, and R. A. D. Bathgate Defining the LGR8 Residues Involved in Binding Insulin-Like Peptide 3 Mol. Endocrinol., July 1, 2007; 21(7): 1699 - 1712. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. T. van der Westhuizen, T. D. Werry, P. M. Sexton, and R. J. Summers The Relaxin Family Peptide Receptor 3 Activates Extracellular Signal-Regulated Kinase 1/2 through a Protein Kinase C-Dependent Mechanism Mol. Pharmacol., June 1, 2007; 71(6): 1618 - 1629. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X.-l. Moore, S.-l. Tan, C.-y. Lo, L. Fang, Y.-D. Su, X.-M. Gao, E. A. Woodcock, R. J. Summers, G. W. Tregear, R. A. D. Bathgate, et al. Relaxin Antagonizes Hypertrophy and Apoptosis in Neonatal Rat Cardiomyocytes Endocrinology, April 1, 2007; 148(4): 1582 - 1589. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Feng, I. U. Agoulnik, N. V. Bogatcheva, A. A. Kamat, B. Kwabi-Addo, R. Li, G. Ayala, M. M. Ittmann, and A. I. Agoulnik Relaxin Promotes Prostate Cancer Progression Clin. Cancer Res., March 15, 2007; 13(6): 1695 - 1702. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Kern, A. I. Agoulnik, and G. D. Bryant-Greenwood The Low-Density Lipoprotein Class A Module of the Relaxin Receptor (Leucine-Rich Repeat Containing G-Protein Coupled Receptor 7): Its Role in Signaling and Trafficking to the Cell Membrane Endocrinology, March 1, 2007; 148(3): 1181 - 1194. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. D. Silvertown, J. C. Symes, A. Neschadim, T. Nonaka, J. C. H. Kao, A. J. S. Summerlee, and J. A. Medin Analog of H2 relaxin exhibits antagonistic properties and impairs prostate tumor growth FASEB J, March 1, 2007; 21(3): 754 - 765. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. J. Hopkins, S. Layfield, T. Ferraro, R. A. D. Bathgate, and P. R. Gooley The NMR Solution Structure of the Relaxin (RXFP1) Receptor Lipoprotein Receptor Class A Module and Identification of Key Residues in the N-terminal Region of the Module That Mediate Receptor Activation J. Biol. Chem., February 9, 2007; 282(6): 4172 - 4184. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. J. Scott, S. Layfield, Y. Yan, S. Sudo, A. J. W. Hsueh, G. W. Tregear, and R. A. D. Bathgate Characterization of Novel Splice Variants of LGR7 and LGR8 Reveals That Receptor Signaling Is Mediated by Their Unique Low Density Lipoprotein Class A Modules J. Biol. Chem., November 17, 2006; 281(46): 34942 - 34954. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. D. Silvertown, J. S. Walia, A. J. Summerlee, and J. A. Medin Functional Expression of Mouse Relaxin and Mouse Relaxin-3 in the Lung from an Ebola Virus Glycoprotein-Pseudotyped Lentivirus via Tracheal Delivery Endocrinology, August 1, 2006; 147(8): 3797 - 3808. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. L. Halls, R. A. D. Bathgate, and R. J. Summers Relaxin Family Peptide Receptors RXFP1 and RXFP2 Modulate cAMP Signaling by Distinct Mechanisms Mol. Pharmacol., July 1, 2006; 70(1): 214 - 226. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. P. Del Borgo, R. A. Hughes, R. A. D. Bathgate, F. Lin, K. Kawamura, and J. D. Wade Analogs of Insulin-like Peptide 3 (INSL3) B-chain Are LGR8 Antagonists in Vitro and in Vivo J. Biol. Chem., May 12, 2006; 281(19): 13068 - 13074. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
 |
 |
 |
|
 |
 |
 |
