help button home button Endocrine Society Endocrinology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Full Text (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
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 Request Copyright Permission
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Behar, V.
Right arrow Articles by Suva, L. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Behar, V.
Right arrow Articles by Suva, L. J.

Endocrinology, Vol 137, 2748-2757, Copyright © 1996 by Endocrine Society

ARTICLES

The human PTH2 receptor: binding and signal transduction properties of the stably expressed recombinant receptor

V Behar, M Pines, C Nakamoto, Z Greenberg, A Bisello, SM Stueckle, R Bessalle, TB Usdin, M Chorev, M Rosenblatt and LJ Suva
Division of Bone and Mineral Metabolism, Harvard-Thorndike and Charles A. Dana Laboratories, Boston, Massachusetts 02215, USA.

We have generated a series of stably transfected HEK-293 cell lines expressing the newly identified alternate human PTH receptor (hPTH2 receptor). This receptor subtype is selectively activated by N-terminal PTH-(1-34) and not the corresponding N-terminal (1-34) region of the functionally and structurally related hormone, PTH-related protein (PTHrP). A total of 20 distinct clones displaying different levels of PTH-responsive cAMP production were analyzed. None responded to PTHrP- (1-34). One of these clones (BP-16), displaying maximal PTH responsiveness, was chosen for more detailed evaluation. The BP-16 clone (and the parental HEK-293 cell line lacking both the hPTH/PTHrP receptor and the hPTH2 receptor) were examined for PTH binding, PTH- stimulated cAMP accumulation, PTH-stimulated changes in intracellular calcium ([Ca2+]i) levels, and hPTH2 receptor messenger RNA expression. In addition, we studied the photomediated cross-linking of a potent PTH agonist, namely [Nle8,18,Lys13 (epsilon-pBz2), 2-L-Nal23,Tyr34]bPTH(1- 34)NH2 (K13), to the hPTH2 receptor on BP-16 cells. Photoaffinity cross- linking identified an approximately 90-kDa cell membrane component that was specifically competed by PTH-(1-34) and other receptor-interacting ligands. PTH-(1-34) and K13 are potent stimulators of both cAMP accumulation and increases in (Ca2+]i levels, and both bind to the hPTH2 receptor with high affinity (apparent Kd, 2.8 +/- 0.9 x 10(-8) and 8.5 +/- 1.7 x 10(-8) M, respectively). There was no apparent binding, cAMP-stimulating activity, or [Ca 2+]i signaling observed, nor was specific competition vs. binding of a PTH-(1-34) radioligand ([125I]PTH) with PTHrP-(1-34)NH2 found. PTHrP-(1-34) failed to inhibit cross-linking of the hPTH2 receptor by radiolabeled K13 ([125I]K13). However, effective competition vs. [125I]PTH and [125I]K13 binding and [125I]K13 cross-linking were observed with the potent PTH/PTHrP receptor antagonists, PTHrP-(7-34)NH2 and PTH-(7-34)NH2. PTHrP-(7- 34)NH2 was shown to be a partial agonist that weakly stimulates both cAMP accumulation and increases in [Ca 2+]i levels in BP-16 cells. These data suggest that the hPTH2 receptor is distinct from the hPTH/PTHrP receptor in the structural features it requires for ligand binding in the family of PTH and PTHrP peptides.


This article has been cited by other articles:


Home page
 Mol. Endocrinol.Home page
C. A. Syme, L. Zhang, and A. Bisello
Caveolin-1 Regulates Cellular Trafficking and Function of the Glucagon-Like Peptide 1 Receptor
Mol. Endocrinol., December 1, 2006; 20(12): 3400 - 3411.
[Abstract] [Full Text] [PDF]

Home page
 Endocr. Rev.Home page
T. M. Murray, L. G. Rao, P. Divieti, and F. R. Bringhurst
Parathyroid Hormone Secretion and Action: Evidence for Discrete Receptors for the Carboxyl-Terminal Region and Related Biological Actions of Carboxyl- Terminal Ligands
Endocr. Rev., February 1, 2005; 26(1): 78 - 113.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
A. Bisello, D. Manen, D. D. Pierroz, T. B. Usdin, R. Rizzoli, and S. L. Ferrari
Agonist-Specific Regulation of Parathyroid Hormone (PTH) Receptor Type 2 Activity: Structural and Functional Analysis of PTH- and Tuberoinfundibular Peptide (TIP) 39-Stimulated Desensitization and Internalization
Mol. Endocrinol., June 1, 2004; 18(6): 1486 - 1498.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
R. C. Gensure, B. Ponugoti, Y. Gunes, M. R. Papasani, B. Lanske, M. Bastepe, D. A. Rubin, and H. Juppner
Identification and Characterization of Two Parathyroid Hormone-Like Molecules in Zebrafish
Endocrinology, April 1, 2004; 145(4): 1634 - 1639.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
A. Bisello, M. Chorev, M. Rosenblatt, L. Monticelli, D. F. Mierke, and S. L. Ferrari
Selective Ligand-induced Stabilization of Active and Desensitized Parathyroid Hormone Type 1 Receptor Conformations
J. Biol. Chem., October 4, 2002; 277(41): 38524 - 38530.
[Abstract] [Full Text] [PDF]

Home page
 Nephrol Dial TransplantHome page
W. G. Goodman, I. B. Salusky, and H. Juppner
New lessons from old assays: parathyroid hormone (PTH), its receptors, and the potential biological relevance of PTH fragments
Nephrol. Dial. Transplant., October 1, 2002; 17(10): 1731 - 1736.
[Full Text] [PDF]

Home page
 EndocrinologyHome page
M. R. John, M. Arai, D. A. Rubin, K. B. Jonsson, and H. Juppner
Identification and Characterization of the Murine and Human Gene Encoding the Tuberoinfundibular Peptide of 39 Residues
Endocrinology, March 1, 2002; 143(3): 1047 - 1057.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
C. P. Goold, T. B. Usdin, and S. R. J. Hoare
Regions in Rat and Human Parathyroid Hormone (PTH) 2 Receptors Controlling Receptor Interaction with PTH and with Antagonist Ligands
J. Pharmacol. Exp. Ther., November 1, 2001; 299(2): 678 - 690.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
H. L. Ward, C. J. Small, K. G. Murphy, A. R. Kennedy, M. A. Ghatei, and S. R. Bloom
The Actions of Tuberoinfundibular Peptide on the Hypothalamo-Pituitary Axes
Endocrinology, August 1, 2001; 142(8): 3451 - 3456.
[Abstract] [Full Text] [PDF]

Home page
 Physiol. Rev.Home page
E. Feraille and A. Doucet
Sodium-Potassium-Adenosinetriphosphatase-Dependent Sodium Transport in the Kidney: Hormonal Control
Physiol Rev, January 1, 2001; 81(1): 345 - 418.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
A. D. Short and C. W. Taylor
Parathyroid Hormone Controls the Size of the Intracellular Ca2+ Stores Available to Receptors Linked to Inositol Trisphosphate Formation
J. Biol. Chem., January 21, 2000; 275(3): 1807 - 1813.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
R. R. Miles, J. P. Sluka, R. F. Santerre, L. V. Hale, L. Bloem, G. Boguslawski, K. Thirunavukkarasu, J. M. Hock, and J. E. Onyia
Dynamic Regulation of RGS2 in Bone: Potential New Insights into Parathyroid Hormone Signaling Mechanisms
Endocrinology, January 1, 2000; 141(1): 28 - 36.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
S. L. Ferrari, V. Behar, M. Chorev, M. Rosenblatt, and A. Bisello
Endocytosis of Ligand-Human Parathyroid Hormone Receptor 1 Complexes Is Protein Kinase C-dependent and Involves beta -Arrestin2. REAL-TIME MONITORING BY FLUORESCENCE MICROSCOPY
J. Biol. Chem., October 15, 1999; 274(42): 29968 - 29975.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
S. R. J. Hoare, T. I. Bonner, and T. B. Usdin
Comparison of Rat and Human Parathyroid Hormone 2 (PTH2) Receptor Activation: PTH Is a Low Potency Partial Agonist at the Rat PTH2 Receptor
Endocrinology, October 1, 1999; 140(10): 4419 - 4425.
[Abstract] [Full Text]

Home page
 EndocrinologyHome page
V. Behar, A. Bisello, M. Rosenblatt, and M. Chorev
Direct Identification of Two Contact Sites for Parathyroid Hormone (PTH) in the Novel PTH-2 Receptor using Photoaffinity Cross-Linking
Endocrinology, September 1, 1999; 140(9): 4251 - 4261.
[Abstract] [Full Text]

Home page
 Clin. Chem.Home page
G. R. Mundy and T. A. Guise
Hormonal Control of Calcium Homeostasis
Clin. Chem., August 1, 1999; 45(8): 1347 - 1352.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
T. B. Usdin, J. Hilton, T. Vertesi, G. Harta, G. Segre, and E. Mezey
Distribution of the Parathyroid Hormone 2 Receptor in Rat: Immunolocalization Reveals Expression by Several Endocrine Cells
Endocrinology, July 1, 1999; 140(7): 3363 - 3371.
[Abstract] [Full Text]

Home page
 EndocrinologyHome page
R. L. Sutliff, C. S. Weber, J. Qian, M. L. Miller, T. L. Clemens, and R. J. Paul
Vasorelaxant Properties of Parathyroid Hormone-Related Protein in the Mouse: Evidence for Endothelium Involvement Independent of Nitric Oxide Formation
Endocrinology, May 1, 1999; 140(5): 2077 - 2083.
[Abstract] [Full Text]

Home page
 EndocrinologyHome page
J. Qian, J. N. Lorenz, S. Maeda, R. L. Sutliff, C. Weber, T. Nakayama, M. C. Colbert, R. J. Paul, J. A. Fagin, and T. L. Clemens
Reduced Blood Pressure and Increased Sensitivity of the Vasculature to Parathyroid Hormone-Related Protein (PTHrP) in Transgenic Mice Overexpressing the PTH/PTHrP Receptor in Vascular Smooth Muscle
Endocrinology, April 1, 1999; 140(4): 1826 - 1833.
[Abstract] [Full Text]

Home page
 Mol. Endocrinol.Home page
A. E. Adams, A. Bisello, M. Chorev, M. Rosenblatt, and L. J. Suva
Arginine 186 in the Extracellular N-Terminal Region of the Human Parathyroid Hormone 1 Receptor Is Essential for Contact with Position 13 of the Hormone
Mol. Endocrinol., November 1, 1998; 12(11): 1673 - 1683.
[Abstract] [Full Text]

Home page
 J. Biol. Chem.Home page
A. Bisello, A. E. Adams, D. F. Mierke, M. Pellegrini, M. Rosenblatt, L. J. Suva, and M. Chorev
Parathyroid Hormone-Receptor Interactions Identified Directly by Photocross-linking and Molecular Modeling Studies
J. Biol. Chem., August 28, 1998; 273(35): 22498 - 22505.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
P. R. Turner, S. Mefford, T. Bambino, and R. A. Nissenson
Transmembrane Residues Together with the Amino Terminus Limit the Response of the Parathyroid Hormone (PTH) 2 Receptor to PTH-related Peptide
J. Biol. Chem., February 13, 1998; 273(7): 3830 - 3837.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
J. A. Clark, T. I. Bonner, A. S. Kim, and T. B. Usdin
Multiple Regions of Ligand Discrimination Revealed by Analysis of Chimeric Parathyroid Hormone 2 (PTH2) and PTH/PTH-Related Peptide (PTHrP) Receptors
Mol. Endocrinol., February 1, 1998; 12(2): 193 - 206.
[Abstract] [Full Text]

Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
S. Fukayama, M. Royo, M. Sugita, A. Imrich, M. Chorev, L. J. Suva, M. Rosenblatt, and A. H. Tashjian Jr.
New insights into interactions between the human PTH/PTHrP receptor and agonist/antagonist binding
Am J Physiol Endocrinol Metab, February 1, 1998; 274(2): E297 - E303.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
S. Yamamoto, I. Morimoto, K. Zeki, Y. Ueta, H. Yamashita, H. Kannan, and S. Eto
Centrally Administered Parathyroid Hormone (PTH)-Related Protein(1-34) But Not PTH(1-34) Stimulates Arginine-Vasopressin Secretion and Its Messenger Ribonucleic Acid Expression in Supraoptic Nucleus of the Conscious Rats
Endocrinology, January 1, 1998; 139(1): 383 - 388.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
A.-S. Jobert, C. Leroy, D. Butlen, and C. Silve
Parathyroid Hormone-Induced Calcium Release from Intracellular Stores in a Human Kidney Cell Line in the Absence of Stimulation of Cyclic Adenosine 3',5'-Monophosphate Production
Endocrinology, December 1, 1997; 138(12): 5282 - 5292.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
S. Yamamoto, I. Morimoto, N. Yanagihara, K. Zeki, T. Fujihira, F. Izumi, H. Yamashita, and S. Eto
Parathyroid Hormone-Related Peptide-(1-34) [PTHrP- (1-34)] Induces Vasopressin Release from the Rat Supraoptic Nucleus in Vitro through a Novel Receptor Distinct from a Type I or Type II PTH/PTHrP Receptor
Endocrinology, May 1, 1997; 138(5): 2066 - 2072.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Endocrinology Endocrine Reviews J. Clin. End. & Metab.
Molecular Endocrinology Recent Prog. Horm. Res. All Endocrine Journals
Copyright © 1996 by The Endocrine Society