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Science 21 September 1990:
Vol. 249. no. 4975, pp. 1423 - 1425
DOI: 10.1126/science.2169649
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Articles

Science, Vol 249, Issue 4975, 1423-1425
Copyright © 1990 by American Association for the Advancement of Science

articles

An insertion in the human thyrotropin receptor critical for high affinity hormone binding

HL Wadsworth, GD Chazenbalk, Y Nagayama, D Russo, and B Rapoport

Department of Medicine, Veterans Administration Medical Center, San Francisco, CA 94121.

Thyrotropin (TSH), luteinizing hormone (LH), and chorionic gonadotropin (CG) are structurally related glycoprotein hormones, which bind to receptors that share a high degree of sequence similarity. However, comparison of the primary amino acid sequences of the TSH and LH-CG receptors reveals two unique insertions of 8 and 50 amino acids in the extracellular domain of the TSH receptor. The functional significance of these insertions were determined by site-directed mutagenesis. Deletion of the 50-amino acid tract (residues 317 to 366) had no effect on TSH binding or on TSH and thyroid-stimulating immunoglobulin (TSI) biological activities. In contrast, either deletion or substitution of the eight-amino acid region (residues 38 to 45) abolished these activities. This eight-amino acid tract near the amino terminus of the TSH receptor appears to be an important site of interaction for both TSH and TSI.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Extended Hormone Binding Site of the Human Thyroid Stimulating Hormone Receptor: DISTINCTIVE ACIDIC RESIDUES IN THE HINGE REGION ARE INVOLVED IN BOVINE THYROID STIMULATING HORMONE BINDING AND RECEPTOR ACTIVATION.
S. Mueller, G. Kleinau, H. Jaeschke, R. Paschke, and G. Krause (2008)
J. Biol. Chem. 283, 18048-18055
   Abstract »    Full Text »    PDF »
The Thyrotropin Receptor Hinge Region Is Not Simply a Scaffold for the Leucine-Rich Domain but Contributes to Ligand Binding and Signal Transduction.
Y. Mizutori, C.-R. Chen, S. M. McLachlan, and B. Rapoport (2008)
Mol. Endocrinol. 22, 1171-1182
   Abstract »    Full Text »    PDF »
Targeted Restoration of Cleavage in a Noncleaving Thyrotropin Receptor Demonstrates that Cleavage Is Insufficient to Enhance Ligand-Independent Activity.
C.-R. Chen, G. D. Chazenbalk, S. M. McLachlan, and B. Rapoport (2003)
Endocrinology 144, 1324-1330
   Abstract »    Full Text »    PDF »
Ligand-dependent Inhibition of Oligomerization at the Human Thyrotropin Receptor.
R. Latif, P. Graves, and T. F. Davies (2002)
J. Biol. Chem. 277, 45059-45067
   Abstract »    Full Text »    PDF »
Thyroid-Stimulating Hormone and Thyroid-Stimulating Hormone Receptor Structure-Function Relationships.
M. W. Szkudlinski, V. Fremont, C. Ronin, and B. D. Weintraub (2002)
Physiol Rev 82, 473-502
   Abstract »    Full Text »    PDF »
On the Functional Importance of Thyrotropin Receptor Intramolecular Cleavage.
G. D. Chazenbalk, K. Tanaka, S. M. McLachlan, and B. Rapoport (1999)
Endocrinology 140, 4516-4520
   Abstract »    Full Text »
Thyrotropin Receptor Cleavage at Site 1 Involves Two Discontinuous Segments at Each End of the Unique 50-Amino Acid Insertion.
K. Tanaka, G. D. Chazenbalk, S. M. McLachlan, and B. Rapoport (1999)
J. Biol. Chem. 274, 2093-2096
   Abstract »    Full Text »    PDF »
The Thyrotropin (TSH)-Releasing Hormone Receptor: Interaction with TSH and Autoantibodies.
B. Rapoport, G. D. Chazenbalk, J. C. Jaume, and S. M. McLachlan (1998)
Endocr. Rev. 19, 673-716
   Abstract »    Full Text »
Thyrotropin Receptor Cleavage at Site 1 Does Not Involve a Specific Amino Acid Motif but Instead Depends on the Presence of the Unique, 50 Amino Acid Insertion.
K. Tanaka, G. D. Chazenbalk, S. M. McLachlan, and B. Rapoport (1998)
J. Biol. Chem. 273, 1959-1963
   Abstract »    Full Text »    PDF »
An N-Linked Glycosylation Motif from the Noncleaving Luteinizing Hormone Receptor Substituted for the Homologous Region (Gly367 to Glu369) of the Thyrotropin Receptor Prevents Cleavage at Its Second, Downstream Site.
A. Kakinuma, G. D. Chazenbalk, K. Tanaka, Y. Nagayama, S. M. McLachlan, and B. Rapoport (1997)
J. Biol. Chem. 272, 28296-28300
   Abstract »    Full Text »    PDF »
Engineering the Human Thyrotropin Receptor Ectodomain from a Non-secreted Form to a Secreted, Highly Immunoreactive Glycoprotein That Neutralizes Autoantibodies in Graves' Patients' Sera.
G. D. Chazenbalk, J. C. Jaume, S. M. McLachlan, and B. Rapoport (1997)
J. Biol. Chem. 272, 18959-18965
   Abstract »    Full Text »    PDF »
Evidence That the Thyrotropin Receptor Ectodomain Contains Not One, But Two, Cleavage Sites.
G. D. Chazenbalk, K. Tanaka, Y. Nagayama, A. Kakinuma, J. C. Jaume, S. M. McLachlan, and B. Rapoport (1997)
Endocrinology 138, 2893-2899
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Temperature Sensitivity of Some Mutants of the Lutropin/Choriogonadotropin Receptor.
J. Jaquette and D. L. Segaloff (1997)
Endocrinology 138, 85-91
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The Amino-terminal Extracellular Domain of the MCP-1 Receptor, but Not the RANTES/MIP-1alpha Receptor, Confers Chemokine Selectivity. EVIDENCE FOR A TWO-STEP MECHANISM FOR MCP-1 RECEPTOR ACTIVATION.
F. S. Monteclaro and I. F. Charo (1996)
J. Biol. Chem. 271, 19084-19092
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Molecular Cloning and Functional Expression of Murine JE (Monocyte Chemoattractant Protein 1) and Murine Macrophage Inflammatory Protein 1alpha Receptors.
L. Boring, J. Gosling, F. S. Monteclaro, A. J. Lusis, C.-L. Tsou, and I. F. Charo (1996)
J. Biol. Chem. 271, 7551-7558
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Shedding of Human Thyrotropin Receptor Ectodomain.
J. Couet, S. Sar, A. Jolivet, M.-T. V. Hai, E. Milgrom, and M. Misrahi (1996)
J. Biol. Chem. 271, 4545-4552
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The Agonist Binding Site on the Bovine Bradykinin B2 Receptor Is Adjacent to a Sulfhydryl and Is Differentiated from the Antagonist Binding Site by Chemical Cross-linking.
M. C. S. Herzig and L. M. F. Leeb-Lundberg (1995)
J. Biol. Chem. 270, 20591-20598
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Cloning and Functional Expression of a Thyrotropin Receptor cDNA from Rat Fat Cells.
T. Endo, K. Ohta, K. Haraguchi, and T. Onaya (1995)
J. Biol. Chem. 270, 10833-10837
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Bioengineering of Human Thyrotropin Superactive Analogs by Site-directed "Lysine-scanning" Mutagenesis. COOPERATIVE EFFECTS BETWEEN PERIPHERAL LOOPS.
H. Leitolf, K. P. T. Tong, M. Grossmann, B. D. Weintraub, and M. W. Szkudlinski (2000)
J. Biol. Chem. 275, 27457-27465
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A Full Biological Response to Autoantibodies in Graves' Disease Requires a Disulfide-bonded Loop in the Thyrotropin Receptor N Terminus Homologous to a Laminin Epidermal Growth Factor-like Domain.
C.-R. Chen, K. Tanaka, G. D. Chazenbalk, S. M. McLachlan, and B. Rapoport (2001)
J. Biol. Chem. 276, 14767-14772
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Oligomerization of the Human Thyrotropin Receptor. FLUORESCENT PROTEIN-TAGGED hTSHR REVEALS POST-TRANSLATIONAL COMPLEXES.
R. Latif, P. Graves, and T. F. Davies (2001)
J. Biol. Chem. 276, 45217-45224
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