| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Molecular Endocrinology, Vol 10, 566-574, Copyright © 1996 by Endocrine Society
ARTICLES |
S Offermanns, A Iida-Klein, GV Segre and MI Simon
Division of Biology, California Institute of Technology, Pasadena 91125, USA.
The PTH/PTH-related peptide (PTHrP) receptor and the calcitonin receptor mediate the action of their physiological ligands by activating two different effectors, adenylyl cyclase and phospholipase C. Whereas regulation of adenylyl cyclase via both receptors is thought to involve the G protein G(s), it is not known whether activation of phospholipase C results from coupling of the receptors to G(q) family members or whether beta gamma-subunit released from receptor-activated G(s) lead to phospholipase C activation. To elucidate the mechanism of this type of dual signaling, we reconstituted the signal transduction of the PTH/PTHrP and the calcitonin receptor in COS-7 and HEK293 cells. In COS-7 cells expressing the receptor alone, addition of the respective ligands resulted in the accumulation of cAMP and inositol phosphates. When cells were cotransfected with the cDNAs of receptor and different alpha-subunits of the Gq family (G alpha q, G alpha 11, G alpha 14, G alpha 15, and G alpha 16, a severalfold increase in the ligand-dependent inositol phosphate production could be observed, indicating that the receptors functionally interacted with all alpha- subunits of the G alpha q family. Additionally, whereas PTH treatment of HEK293 cells coexpressing both the PTH/PTHrP receptor and G alpha q increased both second messengers, the same treatment in cells expressing the PTH/PTHrP receptor alone increased only cAMP. Under all conditions tested, activation of phospholipase C via the PTH/PTHrP and calcitonin receptor required higher ligand concentrations than receptor- mediated adenylyl cyclase activation. Our data strongly support the idea that dual signaling of the PTH/PTHrP and calcitonin receptors is due to the a activation of different G proteins belonging to the G(s) and G(q) families.
This article has been cited by other articles:
 |
|
 |
|
  J. L. Garrido, D. Wheeler, L. L. Vega, P. A. Friedman, and G. Romero Role of Phospholipase D in Parathyroid Hormone Type 1 Receptor Signaling and Trafficking Mol. Endocrinol., December 1, 2009; 23(12): 2048 - 2059. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Wheeler, J. L. Garrido, A. Bisello, Y. K. Kim, P. A. Friedman, and G. Romero Regulation of Parathyroid Hormone Type 1 Receptor Dynamics, Traffic, and Signaling by the Na+/H+ Exchanger Regulatory Factor-1 in Rat Osteosarcoma ROS 17/2.8 Cells Mol. Endocrinol., May 1, 2008; 22(5): 1163 - 1170. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Hinoi, T. Ueshima, H. Hojo, M. Iemata, T. Takarada, and Y. Yoneda Up-regulation of per mRNA Expression by Parathyroid Hormone through a Protein Kinase A-CREB-dependent Mechanism in Chondrocytes J. Biol. Chem., August 18, 2006; 281(33): 23632 - 23642. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J. Mahon, T. M. Bonacci, P. Divieti, and A. V. Smrcka A Docking Site for G Protein {beta}{gamma} Subunits on the Parathyroid Hormone 1 Receptor Supports Signaling through Multiple Pathways Mol. Endocrinol., January 1, 2006; 20(1): 136 - 146. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. J. Rashid, B. F. O'Dowd, and S. R. George Minireview: Diversity and Complexity of Signaling through Peptidergic G Protein-Coupled Receptors Endocrinology, June 1, 2004; 145(6): 2645 - 2652. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Castro, F. Dicker, J.-P. Vilardaga, C. Krasel, M. Bernhardt, and M. J. Lohse Dual Regulation of the Parathyroid Hormone (PTH)/PTH-Related Peptide Receptor Signaling by Protein Kinase C and {beta}-Arrestins Endocrinology, October 1, 2002; 143(10): 3854 - 3865. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 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]
|
|
|
|
 |
|
 H. A. W. Tawfeek, J. Che, F. Qian, and A. B. Abou-Samra Parathyroid hormone receptor internalization is independent of protein kinase A and phospholipase C activation Am J Physiol Endocrinol Metab, September 1, 2001; 281(3): E545 - E557. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Chang, L. Zhang, J. P. Tam, and E. Sanders-Bush Dissecting G Protein-coupled Receptor Signaling Pathways with Membrane-permeable Blocking Peptides. ENDOGENOUS 5-HT2C RECEPTORS IN CHOROID PLEXUS EPITHELIAL CELLS J. Biol. Chem., March 15, 2000; 275(10): 7021 - 7029. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Brydon, F. Roka, L. Petit, P. de Coppet, M. Tissot, P. Barrett, P. J. Morgan, C. Nanoff, A. D. Strosberg, and R. Jockers Dual Signaling of Human Mel1a Melatonin Receptors via Gi2, Gi3, and Gq/11 Proteins Mol. Endocrinol., December 1, 1999; 13(12): 2025 - 2038. [Abstract] [Full Text]
|
|
|
|
|
|
G. Maya-Núñez and P. M. Conn Transcriptional Regulation of the Gonadotropin-Releasing Hormone Receptor Gene Is Mediated in Part by a Putative Repressor Element and by the Cyclic Adenosine 3',5'-Monophosphate Response Element Endocrinology, August 1, 1999; 140(8): 3452 - 3458. [Abstract] [Full Text]
|
|
|
|
|
|
A. M. Cypess, C. G. Unson, C.-R. Wu, and T. P. Sakmar Two Cytoplasmic Loops of the Glucagon Receptor Are Required to Elevate cAMP or Intracellular Calcium J. Biol. Chem., July 2, 1999; 274(27): 19455 - 19464. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Luo, W. Zeng, X. Xu, S. Popov, I. Davignon, T. M. Wilkie, S. M. Mumby, and S. Muallem Alternate Coupling of Receptors to Gs and Gi in Pancreatic and Submandibular Gland Cells J. Biol. Chem., June 18, 1999; 274(25): 17684 - 17690. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. R. J. Hoare, G. de Vries, and T. B. Usdin Measurement of Agonist and Antagonist Ligand-Binding Parameters at the Human Parathyroid Hormone Type 1 Receptor: Evaluation of Receptor States and Modulation by Guanine Nucleotide J. Pharmacol. Exp. Ther., June 1, 1999; 289(3): 1323 - 1333. [Abstract] [Full Text]
|
|
|
|
|
|
M. H. G. Verheijen, R. M. F. Wolthuis, J. L. Bos, and L. H. K. Defize The Ras/Erk Pathway Induces Primitive Endoderm but Prevents Parietal Endoderm Differentiation of F9 Embryonal Carcinoma Cells J. Biol. Chem., January 15, 1999; 274(3): 1487 - 1494. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Lin and P. M. Conn Transcriptional Activation of Gonadotropin-Releasing Hormone (GnRH) Receptor Gene by GnRH: Involvement of Multiple Signal Transduction Pathways Endocrinology, January 1, 1999; 140(1): 358 - 364. [Abstract] [Full Text]
|
|
|
|
 |
|
 D. R. Nussenzveig, M. D. F. C. Matos, and C. N. Thaw Human calcitonin receptor is directly targeted to and retained in the basolateral surface of MDCK cells Am J Physiol Cell Physiol, November 1, 1998; 275(5): C1264 - C1276. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Lin and P. M. Conn Transcriptional Activation of Gonadotropin-Releasing Hormone (GnRH) Receptor Gene by GnRH and Cyclic Adenosine Monophosphate Endocrinology, September 1, 1998; 139(9): 3896 - 3902. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Drissi, F. Lasmoles, V. Le Mellay, P. J. Marie, and M. Lieberherr Activation of Phospholipase C-beta 1 via Galpha q/11 during Calcium Mobilization by Calcitonin Gene-related Peptide J. Biol. Chem., August 7, 1998; 273(32): 20168 - 20174. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Shapira, I. Amit, M. Revach, Y. Oron, and J. F. Battey Galpha 14 and Galpha q Mediate the Response to Trypsin in Xenopus Oocytes J. Biol. Chem., July 31, 1998; 273(31): 19431 - 19436. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Naro, M. Perez, S. Migliaccio, D. L. Galson, P. Orcel, A. Teti, and S. R. Goldring Phospholipase D- and Protein Kinase C Isoenzyme-Dependent Signal Transduction Pathways Activated by the Calcitonin Receptor Endocrinology, July 1, 1998; 139(7): 3241 - 3248. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Stanislaus, S. Ponder, T. H. Ji, and P. M. Conn Gonadotropin-Releasing Hormone Receptor Couples to Multiple G Proteins in Rat Gonadotrophs and in GGH3 Cells: Evidence from Palmitoylation and Overexpression of G proteins Biol Reprod, July 1, 1998; 59(3): 579 - 586. [Abstract] [Full Text]
|
|
|
|
|
|
A. Iida-Klein, J. Guo, M. Takemura, M. T. Drake, J. T. Potts Jr., A. Abou-Samra, F. R. Bringhurst, and G. V. Segre Mutations in the Second Cytoplasmic Loop of the Rat Parathyroid Hormone (PTH)/PTH-related Protein Receptor Result in Selective Loss of PTH-stimulated Phospholipase C Activity J. Biol. Chem., March 14, 1997; 272(11): 6882 - 6889. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. H.G. Verheijen and L. H.K. Defize Parathyroid Hormone Activates Mitogen-activated Protein Kinase via a cAMP-mediated Pathway Independent of Ras J. Biol. Chem., February 7, 1997; 272(6): 3423 - 3429. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Huang, Y. Chen, S. Pratt, T.-H. Chen, T. Bambino, R. A. Nissenson, and D. M. Shoback The N-terminal Region of the Third Intracellular Loop of the Parathyroid Hormone (PTH)/PTH-related Peptide Receptor Is Critical for Coupling to cAMP and Inositol Phosphate/Ca2+ Signal Transduction Pathways J. Biol. Chem., December 27, 1996; 271(52): 33382 - 33389. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-F. Shyu, D. Inoue, R. Baron, and W. C. Horne The Deletion of 14Amino Acids in the Seventh Transmembrane Domain of a Naturally Occurring Calcitonin Receptor Isoform Alters Ligand Binding and Selectively Abolishes Coupling to Phospholipase C J. Biol. Chem., December 6, 1996; 271(49): 31127 - 31134. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K.-L. Laugwitz, H.-J. Weig, A. Moretti, E. Hoffmann, P. Ueblacker, I. Pragst, K. Rosport, A. Schomig, and M. Ungerer Gene Transfer of Heterologous G Protein-Coupled Receptors to Cardiomyocytes : Differential Effects on Contractility Circ. Res., April 13, 2001; 88(7): 688 - 695. [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 |
