MolPharm xPharm- The Comprehensive Pharmacology Reference

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
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
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Kosugi, S.
Right arrow Articles by Shenker, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kosugi, S.
Right arrow Articles by Shenker, A.

Vol. 53, Issue 5, 894-901, May 1998

An Anionic Residue at Position 564 Is Important for Maintaining the Inactive Conformation of the Human Lutropin/Choriogonadotropin Receptor

Shinji Kosugi, Toru Mori, and Andrew Shenker

Department of Laboratory Medicine, Kyoto University School of Medicine, Kyoto 606-8507, Japan (S.K., T.M.), and Division of Endocrinology, Department of Pediatrics, Northwestern University Medical School and Children's Memorial Hospital, Chicago, Illinois 60614 (A.S.)

Gonadotropin-independent, male-limited precocious puberty is caused by a variety of mutations in the lutropin/choriogonadotropin receptor (LHR) that produce constitutive receptor activation. Two of these mutations encode replacement of conserved aspartate residues at positions 564 and 578 with glycine. We previously used site-directed mutagenesis to study the functional role of the Asp578 side chain in transmembrane helix 6, and concluded that it is its ability to serve as a properly positioned interhelical hydrogen bond acceptor, rather than its negative charge, that is important for stabilizing the inactive state of the LHR. We now report the effects of substituting seven different amino acids for the Asp564 residue located at the carboxyl terminus of the third intracellular loop. Glycine, alanine, valine, leucine, phenylalanine, and asparagine produced constitutive activation in a COS-7 cell expression system (3-5-fold increase in basal cAMP), but glutamate did not, indicating that a negative charge at position 564 may be important for maintaining the inactive LHR conformation. Characterization of double-mutant receptors showed that certain substitutions at Asp564 and Asp578 have a cumulative effect on basal receptor activity, perhaps because they mimic different aspects of the activation process normally triggered by hormone binding.

Copyright © 1998 by The American Society for Pharmacology and Experimental Therapeutics


This article has been cited by other articles:


Home page
 EndocrinologyHome page
X. Feng, T. Muller, D. Mizrachi, F. Fanelli, and D. L. Segaloff
An Intracellular Loop (IL2) Residue Confers Different Basal Constitutive Activities to the Human Lutropin Receptor and Human Thyrotropin Receptor through Structural Communication between IL2 and Helix 6, via Helix 3
Endocrinology, April 1, 2008; 149(4): 1705 - 1717.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
E. Ramon, A. Cordomi, L. Bosch, E. Yu. Zernii, I. I. Senin, J. Manyosa, P. P. Philippov, J. J. Perez, and P. Garriga
Critical Role of Electrostatic Interactions of Amino Acids at the Cytoplasmic Region of Helices 3 and 6 in Rhodopsin Conformational Properties and Activation
J. Biol. Chem., May 11, 2007; 282(19): 14272 - 14282.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
L. Montanelli, J. J. J. Van Durme, G. Smits, M. Bonomi, P. Rodien, E. J. Devor, K. Moffat-Wilson, L. Pardo, G. Vassart, and S. Costagliola
Modulation of Ligand Selectivity Associated with Activation of the Transmembrane Region of the Human Follitropin Receptor
Mol. Endocrinol., August 1, 2004; 18(8): 2061 - 2073.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
C. M. Allan, A. Garcia, J. Spaliviero, F.-P. Zhang, M. Jimenez, I. Huhtaniemi, and D. J. Handelsman
Complete Sertoli Cell Proliferation Induced by Follicle-Stimulating Hormone (FSH) Independently of Luteinizing Hormone Activity: Evidence from Genetic Models of Isolated FSH Action
Endocrinology, April 1, 2004; 145(4): 1587 - 1593.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
T. Hirakawa and M. Ascoli
A Constitutively Active Somatic Mutation of the Human Lutropin Receptor Found in Leydig Cell Tumors Activates the Same Families of G Proteins as Germ Line Mutations Associated with Leydig Cell Hyperplasia
Endocrinology, September 1, 2003; 144(9): 3872 - 3878.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
K. Angelova, F. Fanelli, and D. Puett
A Model for Constitutive Lutropin Receptor Activation Based on Molecular Simulation and Engineered Mutations in Transmembrane Helices 6 and 7
J. Biol. Chem., August 23, 2002; 277(35): 32202 - 32213.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
L. M. Salvador, E. Maizels, D. B. Hales, E. Miyamoto, H. Yamamoto, and M. Hunzicker-Dunn
Acute Signaling by the LH Receptor Is Independent of Protein Kinase C Activation
Endocrinology, August 1, 2002; 143(8): 2986 - 2994.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
S. Mukherjee, V. V. Gurevich, A. Preninger, H. E. Hamm, M.-F. Bader, A. T. Fazleabas, L. Birnbaumer, and M. Hunzicker-Dunn
Aspartic Acid 564 in the Third Cytoplasmic Loop of the Luteinizing Hormone/Choriogonadotropin Receptor Is Crucial for Phosphorylation-independent Interaction with Arrestin2
J. Biol. Chem., May 10, 2002; 277(20): 17916 - 17927.
[Abstract] [Full Text] [PDF]

Home page
 Endocr. Rev.Home page
M. Ascoli, F. Fanelli, and D. L. Segaloff
The Lutropin/Choriogonadotropin Receptor, A 2002 Perspective
Endocr. Rev., April 1, 2002; 23(2): 141 - 174.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
T. Hirakawa, C. Galet, and M. Ascoli
MA-10 Cells Transfected with the Human Lutropin/Choriogonadotropin Receptor (hLHR): A Novel Experimental Paradigm to Study the Functional Properties of the hLHR
Endocrinology, March 1, 2002; 143(3): 1026 - 1035.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
S. Nishi, S. Y. Hsu, K. Zell, and A. J. W. Hsueh
Characterization of Two Fly LGR (Leucine-Rich Repeat-Containing, G Protein-Coupled Receptor) Proteins Homologous to Vertebrate Glycoprotein Hormone Receptors: Constitutive Activation of Wild-Type Fly LGR1 But Not LGR2 in Transfected Mammalian Cells
Endocrinology, November 1, 2000; 141(11): 4081 - 4090.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
S. Y. Hsu, M. Kudo, T. Chen, K. Nakabayashi, A. Bhalla, P. J. van der Spek, M. van Duin, and A. J. W. Hsueh
The Three Subfamilies of Leucine-Rich Repeat-Containing G Protein-Coupled Receptors (LGR): Identification of LGR6 and LGR7 and the Signaling Mechanism for LGR7
Mol. Endocrinol., August 1, 2000; 14(8): 1257 - 1271.
[Abstract] [Full Text]

Home page
 Mol. Endocrinol.Home page
A. Schulz, T. Schöneberg, R. Paschke, G. Schultz, and T. Gudermann
Role of the Third Intracellular Loop for the Activation of Gonadotropin Receptors
Mol. Endocrinol., February 1, 1999; 13(2): 181 - 190.
[Abstract] [Full Text]

Home page
 J. Biol. Chem.Home page
K. Nakabayashi, M. Kudo, B. Kobilka, and A. J. W. Hsueh
Activation of the Luteinizing Hormone Receptor Following Substitution of Ser-277 with Selective Hydrophobic Residues in the Ectodomain Hinge Region
J. Biol. Chem., September 22, 2000; 275(39): 30264 - 30271.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
A. Schulz, K. Bruns, P. Henklein, G. Krause, M. Schubert, T. Gudermann, V. Wray, G. Schultz, and T. Schoneberg
Requirement of Specific Intrahelical Interactions for Stabilizing the Inactive Conformation of Glycoprotein Hormone Receptors
J. Biol. Chem., November 22, 2000; 275(48): 37860 - 37869.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
J. A. Ballesteros, A. D. Jensen, G. Liapakis, S. G.F. Rasmussen, L. Shi, U. Gether, and J. A. Javitch
Activation of the beta 2-Adrenergic Receptor Involves Disruption of an Ionic Lock between the Cytoplasmic Ends of Transmembrane Segments 3 and 6
J. Biol. Chem., July 27, 2001; 276(31): 29171 - 29177.
[Abstract] [Full Text] [PDF]


Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 1998 by the American Society for Pharmacology and Experimental Therapeutics