JBC

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Originally published In Press as doi:10.1074/jbc.M009020200 on December 8, 2000

J. Biol. Chem., Vol. 276, Issue 11, 7754-7761, March 16, 2001
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
276/11/7754    most recent
M009020200v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Sun, Y.-M.
Right arrow Articles by Millar, R. P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Sun, Y.-M.
Right arrow Articles by Millar, R. P.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

A Chicken Gonadotropin-releasing Hormone Receptor That Confers Agonist Activity to Mammalian Antagonists
IDENTIFICATION OF D-LYS6 IN THE LIGAND AND EXTRACELLULAR LOOP TWO OF THE RECEPTOR AS DETERMINANTS*

Yuh-Man SunDagger §, Colleen A. FlanaganDagger , Nicola IllingDagger ||, Thomas R. OttDagger **, Robin Sellar**, Bernhard J. FrommeDagger , Janet HapgoodDagger Dagger Dagger , Peter Sharp§§, Stuart C. Sealfon¶¶, and Robert P. MillarDagger ||||

From the Dagger  MRC/UCT Research Unit for Molecular Reproductive Endocrinology and the  Department of Medicine, University of Cape Town, Observatory 7925, South Africa, ** MRC Human Reproductive Sciences Unit, 37 Chalmers Street, Edinburgh EH3 9ET, Scotland, United Kingdom, §§ Division of Integrative Biology, Roslin Institute (Edinburgh), Roslin, Midlothian EH25 9PS, United Kingdom, and the ¶¶ Fishberg Research Center in Neurobiology, the Mount Sinai Medical Center, New York, New York 10029

Mammalian receptors for gonadotropin-releasing hormone (GnRH) have over 85% sequence homology and similar ligand selectivity. Biological studies indicated that the chicken GnRH receptor has a distinct pharmacology, and certain antagonists of mammalian GnRH receptors function as agonists. To explore the structural determinants of this, we have cloned a chicken pituitary GnRH receptor and demonstrated that it has marked differences in primary amino acid sequence (59% homology) and in its interactions with GnRH analogs. The chicken GnRH receptor had high affinity for mammalian GnRH (Ki 4.1 ± 1.2 nM) , similar to the human receptor (Ki 4.8 ± 1.2 nM). But, in contrast to the human receptor, it also had high affinity for chicken GnRH ([Gln8]GnRH) and GnRH II ([His5,Trp7,Tyr8]GnRH) (Ki 5.3 ± 0.5 and 0.6 ± 0.01 nM). Three mammalian receptor antagonists were also pure antagonists in the chicken GnRH receptor. Another three, characterized by D-Lys6 or D-isopropyl-Lys6 moieties, functioned as pure antagonists in the human receptor but were full or partial agonists in the chicken receptor. This suggests that the Lys side chain interacts with functional groups of the chicken GnRH receptor to stabilize it in the active conformation and that these groups are not available in the activated human GnRH receptor. Substitution of the human receptor extracellular loop two with the chicken extracellular loop two identified this domain as capable of conferring agonist activity to mammalian antagonists. Although functioning of antagonists as agonists has been shown to be species-dependent for several GPCRs, the dependence of this on an extracellular domain has not been described.

* This work was supported by the Medical Research Council and National Research Foundation (South Africa), the University of Cape Town, the British Council, the Medical Research Council (UK), the Biotechnology and Biological Sciences Research Council (Competitive Strategic Grant), and National Institutes of Health Grant RO1.DK46943.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The nucleotide sequence(s) reported in this paper has been submitted to the GenBankTM/EMBL Data Bank with accession number(s) AJ304414.

§ Current address: Division of Genomics and Bioinformatics, Roslin Institute, Roslin, Midlothian EH23 9PS, UK.

|| Current address: Dept. of Biochemistry, University of Cape Town, Rondebosch 7700, South Africa.

Dagger Dagger Current address: Dept. of Biochemistry, University of Stellenbosch, Matieland 7602, South Africa.

|||| To whom correspondence should be addressed: MRC Human Reproductive Sciences Unit, 37 Chalmers Street, Edinburgh EH3 9ET, Scotland, UK. Tel.: 131 229 2575; Fax: 131 228 5571.

Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.
Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:


Home page
 EndocrinologyHome page
K. D. G. Pfleger, A. J. Pawson, and R. P. Millar
Changes to Gonadotropin-Releasing Hormone (GnRH) Receptor Extracellular Loops Differentially Affect GnRH Analog Binding and Activation: Evidence for Distinct Ligand-Stabilized Receptor Conformations
Endocrinology, June 1, 2008; 149(6): 3118 - 3129.
[Abstract] [Full Text] [PDF]

Home page
 Hum Reprod UpdateHome page
P. C.K. Leung and J.-H. Choi
Endocrine signaling in ovarian surface epithelium and cancer
Hum. Reprod. Update, March 1, 2007; 13(2): 143 - 162.
[Abstract] [Full Text] [PDF]

Home page
 Biol. Reprod.Home page
M. Shimizu and G. Y. Bedecarrats
Identification of a Novel Pituitary-Specific Chicken Gonadotropin-Releasing Hormone Receptor and Its Splice Variants
Biol Reprod, November 1, 2006; 75(5): 800 - 808.
[Abstract] [Full Text] [PDF]

Home page
 Endocr Relat CancerHome page
J.-H. Choi, K.-C. Choi, N. Auersperg, and P. C K Leung
Differential regulation of two forms of gonadotropin-releasing hormone messenger ribonucleic acid by gonadotropins in human immortalized ovarian surface epithelium and ovarian cancer cells.
Endocr. Relat. Cancer, June 1, 2006; 13(2): 641 - 651.
[Abstract] [Full Text] [PDF]

Home page
 J EndocrinolHome page
A. Leanos-Miranda, A. Ulloa-Aguirre, L. A Cervini, J. A. Janovick, J. Rivier, and P M. Conn
Identification of new gonadotrophin-releasing hormone partial agonists.
J. Endocrinol., June 1, 2006; 189(3): 509 - 517.
[Abstract] [Full Text] [PDF]

Home page
 Biol. Reprod.Home page
A. M. Navratil, T. A. Farmerie, J. Bogerd, T. M. Nett, and C. M. Clay
Differential Impact of Intracellular Carboxyl Terminal Domains on Lipid Raft Localization of the Murine Gonadotropin-Releasing Hormone Receptor
Biol Reprod, May 1, 2006; 74(5): 788 - 797.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
D. K. Barnett, T. M. Bunnell, R. P. Millar, and D. H. Abbott
Gonadotropin-Releasing Hormone II Stimulates Female Sexual Behavior in Marmoset Monkeys
Endocrinology, January 1, 2006; 147(1): 615 - 623.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
P. E. Barran, R. W. Roeske, A. J. Pawson, R. Sellar, M. T. Bowers, K. Morgan, Z.-L. Lu, M. Tsuda, T. Kusakabe, and R. P. Millar
Evolution of Constrained Gonadotropin-releasing Hormone Ligand Conformation and Receptor Selectivity
J. Biol. Chem., November 18, 2005; 280(46): 38569 - 38575.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
Z.-L. Lu, R. Gallagher, R. Sellar, M. Coetsee, and R. P. Millar
Mutations Remote from the Human Gonadotropin-releasing Hormone (GnRH) Receptor-binding Sites Specifically Increase Binding Affinity for GnRH II but Not GnRH I: EVIDENCE FOR LIGAND-SELECTIVE, RECEPTOR-ACTIVE CONFORMATIONS
J. Biol. Chem., August 19, 2005; 280(33): 29796 - 29803.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
M. R. Silver, N. V. Nucci, A. R. Root, K. L. Reed, and S. A. Sower
Cloning and Characterization of a Functional Type II Gonadotropin-Releasing Hormone Receptor with a Lengthy Carboxy-Terminal Tail from an Ancestral Vertebrate, the Sea Lamprey
Endocrinology, August 1, 2005; 146(8): 3351 - 3361.
[Abstract] [Full Text] [PDF]

Home page
 J Mol EndocrinolHome page
N. Moncaut, G. Somoza, D. M Power, and A. V M Canario
Five gonadotrophin-releasing hormone receptors in a teleost fish: isolation, tissue distribution and phylogenetic relationships
J. Mol. Endocrinol., June 1, 2005; 34(3): 767 - 779.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
A. J. Pawson, S. Maudsley, K. Morgan, L. Davidson, Z. Naor, and R. P. Millar
Inhibition of Human Type I Gonadotropin-Releasing Hormone Receptor (GnRHR) Function by Expression of a Human Type II GnRHR Gene Fragment
Endocrinology, June 1, 2005; 146(6): 2639 - 2649.
[Abstract] [Full Text] [PDF]

Home page
 J EndocrinolHome page
H Yin, K Ukena, T Ubuka, and K Tsutsui
A novel G protein-coupled receptor for gonadotropin-inhibitory hormone in the Japanese quail (Coturnix japonica): identification, expression and binding activity
J. Endocrinol., January 1, 2005; 184(1): 257 - 266.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
C. J. Caunt, J. N. Hislop, E. Kelly, A.-L. Matharu, L. D. Green, K. R. Sedgley, A. R. Finch, and C. A. McArdle
Regulation of Gonadotropin-Releasing Hormone Receptors by Protein Kinase C: Inside Out Signalling and Evidence for Multiple Active Conformations
Endocrinology, August 1, 2004; 145(8): 3594 - 3602.
[Abstract] [Full Text] [PDF]

Home page
 Biol. Reprod.Home page
L. A. Mongiat, V. A. Lux-Lantos, and C. Libertun
Evidence for Different Gonadotropin-Releasing Hormone Response Sites in Rat Ovarian and Pituitary Cells
Biol Reprod, August 1, 2004; 71(2): 464 - 469.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
A. J. Pawson, S. R. Maudsley, J. Lopes, A. A. Katz, Y.-M. Sun, J. S. Davidson, and R. P. Millar
Multiple Determinants for Rapid Agonist-Induced Internalization of a Nonmammalian Gonadotropin-Releasing Hormone Receptor: A Putative Palmitoylation Site and Threonine Doublet within the Carboxyl-Terminal Tail Are Critical
Endocrinology, September 1, 2003; 144(9): 3860 - 3871.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
J. Xu, X. Luo, and N. Chegini
Differential Expression, Regulation, and Induction of Smads, Transforming Growth Factor-{beta} Signal Transduction Pathway in Leiomyoma, and Myometrial Smooth Muscle Cells and Alteration by Gonadotropin-Releasing Hormone Analog
J. Clin. Endocrinol. Metab., March 1, 2003; 88(3): 1350 - 1361.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
J. L. Temple, R. P. Millar, and E. F. Rissman
An Evolutionarily Conserved Form of Gonadotropin-Releasing Hormone Coordinates Energy and Reproductive Behavior
Endocrinology, January 1, 2003; 144(1): 13 - 19.
[Abstract] [Full Text] [PDF]

Home page
 Biol. Reprod.Home page
W. van Biljon, S. Wykes, S. Scherer, S.A. Krawetz, and J. Hapgood
Type II Gonadotropin-Releasing Hormone Receptor Transcripts in Human Sperm
Biol Reprod, December 1, 2002; 67(6): 1741 - 1749.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
K. D. G. Pfleger, J. Bogerd, and R. P. Millar
Conformational Constraint of Mammalian, Chicken, and Salmon GnRHs, But Not GnRH II, Enhances Binding at Mammalian and Nonmammalian Receptors: Evidence for Preconfiguration of GnRH II
Mol. Endocrinol., September 1, 2002; 16(9): 2155 - 2162.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
K. Ray and J. Northup
Evidence for Distinct Cation and Calcimimetic Compound (NPS 568) Recognition Domains in the Transmembrane Regions of the Human Ca2+ Receptor
J. Biol. Chem., May 17, 2002; 277(21): 18908 - 18913.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
T. R. Ott, B. E. Troskie, R. W. Roeske, N. Illing, C. A. Flanagan, and R. P. Millar
Two Mutations in Extracellular Loop 2 of the Human GnRH Receptor Convert an Antagonist to an Agonist
Mol. Endocrinol., May 1, 2002; 16(5): 1079 - 1088.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
K. Okubo, S. Nagata, R. Ko, H. Kataoka, Y. Yoshiura, H. Mitani, M. Kondo, K. Naruse, A. Shima, and K. Aida
Identification and Characterization of Two Distinct GnRH Receptor Subtypes in a Teleost, the Medaka Oryzias latipes
Endocrinology, November 1, 2001; 142(11): 4729 - 4739.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
R. Millar, S. Lowe, D. Conklin, A. Pawson, S. Maudsley, B. Troskie, T. Ott, M. Millar, G. Lincoln, R. Sellar, et al.
A novel mammalian receptor for the evolutionarily conserved type II GnRH
PNAS, August 1, 2001; (2001) 141048498.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
R. Millar, S. Lowe, D. Conklin, A. Pawson, S. Maudsley, B. Troskie, T. Ott, M. Millar, G. Lincoln, R. Sellar, et al.
A novel mammalian receptor for the evolutionarily conserved type II GnRH
PNAS, August 14, 2001; 98(17): 9636 - 9641.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
 All ASBMB Journals   Molecular and Cellular Proteomics 
 Journal of Lipid Research   ASBMB Today 
Copyright © 2001 by the American Society for Biochemistry and Molecular Biology.