Molecular Endocrinology, Vol 6, 551-556, Copyright © 1992 by Endocrine Society

ARTICLES

A recombinant calcitonin receptor independently stimulates 3',5'-cyclic adenosine monophosphate and Ca2+/inositol phosphate signaling pathways

O Chabre, BR Conklin, HY Lin, HF Lodish, E Wilson, HE Ives, L Catanzariti, BA Hemmings and HR Bourne
Department of Pharmacology, University of California, San Francisco 94113.

Calcitonin (CT), a polypeptide hormone, regulates calcium homeostasis by activating surface receptors coupled to stimulation of adenylyl cyclase in bone and kidney cells. CT has also been reported to increase cytoplasmic Ca2+ in osteoclasts and renal tubule cells. Signaling pathways activated by a recombinant porcine renal calcitonin receptor transiently expressed in HEK-293 cells were studied. In cells expressing the recombinant CT receptor, salmon CT stimulated cAMP accumulation (EC50, 0.16 nM) and synthesis of inositol phosphates (IP; EC50, 3.7 nM). Two other recombinant receptors, the m1-muscarinic acetylcholine receptor and the LH receptor, activated synthesis of either IP or cAMP, respectively, but not both. Stable expression of the CT receptor in a CT receptor-deficient cell line, M18, restored the cells' ability to increase cytoplasmic Ca2+ in response to salmon CT. These results show that a single recombinant CT receptor can independently activate effector pathways mediated by cAMP and IP/Ca2+.

This article has been cited by other articles:

				M. Nakamura, B. Han, T. Nishishita, Y. Bai, and K. Kakudo Calcitonin targets extracellular signal-regulated kinase signaling pathway in human cancers J. Mol. Endocrinol., December 1, 2007; 39(6): 375 - 384. [Abstract] [Full Text] [PDF]

				Q. Li, M. K. Bagchi, and I. C. Bagchi Identification of a Signaling Pathway Involving Progesterone Receptor, Calcitonin, and Tissue Tranglutaminase in Ishikawa Endometrial Cells Endocrinology, May 1, 2006; 147(5): 2147 - 2154. [Abstract] [Full Text] [PDF]

				M. Marzia, R. Chiusaroli, L. Neff, N.-Y. Kim, A. H. Chishti, R. Baron, and W. C. Horne Calpain Is Required for Normal Osteoclast Function and Is Down-regulated by Calcitonin J. Biol. Chem., April 7, 2006; 281(14): 9745 - 9754. [Abstract] [Full Text] [PDF]

				R. J. W. Diepens, E. den Dekker, M. Bens, A. F. Weidema, A. Vandewalle, R. J. M. Bindels, and J. G. J. Hoenderop Characterization of a murine renal distal convoluted tubule cell line for the study of transcellular calcium transport Am J Physiol Renal Physiol, March 1, 2004; 286(3): F483 - F489. [Abstract] [Full Text]

				T. Seck, R. Baron, and W. C. Horne The Alternatively Spliced {Delta}e13 Transcript of the Rabbit Calcitonin Receptor Dimerizes with the C1a Isoform and Inhibits Its Surface Expression J. Biol. Chem., June 13, 2003; 278(25): 23085 - 23093. [Abstract] [Full Text] [PDF]

				Q. Li, J. Wang, D. R. Armant, M. K. Bagchi, and I. C. Bagchi Calcitonin Down-regulates E-cadherin Expression in Rodent Uterine Epithelium during Implantation J. Biol. Chem., November 22, 2002; 277(48): 46447 - 46455. [Abstract] [Full Text] [PDF]

				C. H. Berlot A Highly Effective Dominant Negative alpha s Construct Containing Mutations That Affect Distinct Functions Inhibits Multiple Gs-coupled Receptor Signaling Pathways J. Biol. Chem., May 31, 2002; 277(23): 21080 - 21085. [Abstract] [Full Text] [PDF]

				S. Wada, S. Yasuda, T. Nagai, T. Maeda, S. Kitahama, S. Suda, D. M. Findlay, M. Iitaka, and S. Katayama Regulation of Calcitonin Receptor by Glucocorticoid in Human Osteoclast-Like Cells Prepared in Vitro Using Receptor Activator of Nuclear Factor-{{kappa}}B Ligand and Macrophage Colony-Stimulating Factor Endocrinology, April 1, 2001; 142(4): 1471 - 1478. [Abstract] [Full Text]

				D. M. Kemp and J. F. Habener Insulinotropic Hormone Glucagon-Like Peptide 1 (GLP-1) Activation of Insulin Gene Promoter Inhibited by p38 Mitogen-Activated Protein Kinase Endocrinology, March 1, 2001; 142(3): 1179 - 1187. [Abstract] [Full Text] [PDF]

				A. Samura, S. Wada, S. Suda, M. Iitaka, and S. Katayama Calcitonin Receptor Regulation and Responsiveness to Calcitonin in Human Osteoclast-Like Cells Prepared in Vitro using Receptor Activator of Nuclear Factor-{kappa}B Ligand and Macrophage Colony-Stimulating Factor Endocrinology, October 1, 2000; 141(10): 3774 - 3782. [Abstract] [Full Text] [PDF]

				K. Furuya, R. J. Milchak, K. M. Schegg, J. Zhang, S. S. Tobe, G. M. Coast, and D. A. Schooley Cockroach diuretic hormones: Characterization of a calcitonin-like peptide in insects PNAS, June 6, 2000; 97(12): 6469 - 6474. [Abstract] [Full Text] [PDF]

				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]

				P. Orcel, H. Tajima, Y. Murayama, T. Fujita, S. M. Krane, E. Ogata, S. R. Goldring, and I. Nishimoto Multiple Domains Interacting with Gs in the Porcine Calcitonin Receptor Mol. Endocrinol., January 1, 2000; 14(1): 170 - 182. [Abstract] [Full Text]

				L. Oliveira, A.C.M. Paiva, and G. Vriend A low resolution model for the interaction of G proteins with G protein-coupled receptors Protein Eng. Des. Sel., December 1, 1999; 12(12): 1087 - 1095. [Abstract] [Full Text] [PDF]

				N. YOSHIDA, T. YOSHIDA, A. NAKAMURA, T. MONKAWA, M. HAYASHI, and T. SARUTA Calcitonin Induces 25-Hydroxyvitamin D3 1{alpha}-Hydroxylase mRNA Expression via Protein Kinase C Pathway in LLC-PK1 Cells J. Am. Soc. Nephrol., December 1, 1999; 10(12): 2474 - 2479. [Abstract] [Full Text]

				Z. Zhang, L. Hernandez-Lagunas, W. C. Horne, and R. Baron Cytoskeleton-dependent Tyrosine Phosphorylation of the p130Cas Family Member HEF1 Downstream of the G Protein-coupled Calcitonin Receptor. CALCITONIN INDUCES THE ASSOCIATION OF HEF1, PAXILLIN, AND FOCAL ADHESION KINASE J. Biol. Chem., August 27, 1999; 274(35): 25093 - 25098. [Abstract] [Full Text] [PDF]

				L. A. Arbogast, G. V. Shah, and J. L. Voogt 3',5' Cyclic Adenosine Monophosphate Mediates the Salmon Calcitonin-Induced Increase in Hypothalamic Tyrosine Hydroxylase Activity Endocrinology, July 1, 1999; 140(7): 3273 - 3281. [Abstract] [Full Text]

				D. Inoue, C. Shih, D. L. Galson, S. R. Goldring, W. C. Horne, and R. Baron Calcitonin-Dependent Down-Regulation of the Mouse C1a Calcitonin Receptor in Cells of the Osteoclast Lineage Involves a Transcriptional Mechanism Endocrinology, March 1, 1999; 140(3): 1060 - 1068. [Abstract] [Full Text]

				O. Chabre, P. Liakos, J. Vivier, P. Chaffanjon, F. Labat-Moleur, M. Martinie, S. P. Bottari, I. Bachelot, E. M. Chambaz, G. Defaye, et al. Cushing's Syndrome due to a Gastric Inhibitory Polypeptide-Dependent Adrenal Adenoma: Insights into Hormonal Control of Adrenocortical Tumorigenesis J. Clin. Endocrinol. Metab., September 1, 1998; 83(9): 3134 - 3143. [Abstract] [Full Text]

				S. C. Ganguli, C.-G. Park, M. H. Holtmann, E. M. Hadac, T. P. Kenakin, and L. J. Miller Protean Effects of a Natural Peptide Agonist of the G Protein-Coupled Secretin Receptor Demonstrated by Receptor Mutagenesis J. Pharmacol. Exp. Ther., August 1, 1998; 286(2): 593 - 598. [Abstract] [Full Text]

				J. A. Flores, C. Aguirre, O. P. Sharma, and J. D. Veldhuis Luteinizing Hormone (LH) Stimulates Both Intracellular Calcium Ion ([Ca2+]i) Mobilization and Transmembrane Cation Influx in Single Ovarian (Granulosa) Cells: Recruitment as a Cellular Mechanism of LH-[Ca2+]i Dose Response Endocrinology, August 1, 1998; 139(8): 3606 - 3612. [Abstract] [Full Text] [PDF]

				Y. Chen, J.-F. Shyu, A. Santhanagopal, D. Inoue, J.-P. David, S. J. Dixon, W. C. Horne, and R. Baron The Calcitonin Receptor Stimulates Shc Tyrosine Phosphorylation and Erk1/2 Activation. INVOLVEMENT OF Gi, PROTEIN KINASE C, AND CALCIUM J. Biol. Chem., July 31, 1998; 273(31): 19809 - 19816. [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]

				L. H. Hansen, J. Gromada, P. Bouchelouche, T. Whitmore, L. Jelinek, W. Kindsvogel, and E. Nishimura Glucagon-mediated Ca2+ signaling in BHK cells expressing cloned human glucagon receptors Am J Physiol Cell Physiol, June 1, 1998; 274(6): C1552 - C1562. [Abstract] [Full Text] [PDF]

				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]

				T. K. Chatterjee, R. V. Sharma, and R. A. Fisher Molecular Cloning of a Novel Variant of the Pituitary Adenylate Cyclase-activating Polypeptide (PACAP) Receptor That Stimulates Calcium Influx by Activation of L-type Calcium Channels J. Biol. Chem., December 13, 1996; 271(50): 32226 - 32232. [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]

				J. Liu and Jür. Wess Different Single Receptor Domains Determine the Distinct G Protein Coupling Profiles of Members of the Vasopressin Receptor Family J. Biol. Chem., April 12, 1996; 271(15): 8772 - 8778. [Abstract] [Full Text] [PDF]

				A. Teti, R. Paniccia, and S. R. Goldring Calcitonin Increases Cytosolic Free Calcium Concentration via Capacitative Calcium Influx J. Biol. Chem., July 14, 1995; 270(28): 16666 - 16670. [Abstract] [Full Text] [PDF]

				P. de la Peña, D. del Camino, L. A. Pardo, P. Domínguez, and F. Barros G(s) Couples Thyrotropin-releasing Hormone Receptors Expressed in Xenopus Oocytes to Phospholipase C J. Biol. Chem., February 24, 1995; 270(8): 3554 - 3559. [Abstract] [Full Text] [PDF]

				S. Arkett, S. Dixon, and S. Sims Lamellipod extension and K+ current in osteoclasts are regulated by different types of G proteins J. Cell Sci., January 2, 1994; 107(2): 517 - 526. [Abstract] [PDF]

				L. Jelinek, S Lok, G. Rosenberg, R. Smith, F. Grant, S Biggs, P. Bensch, J. Kuijper, P. Sheppard, C. Sprecher, et al. Expression cloning and signaling properties of the rat glucagon receptor Science, March 12, 1993; 259(5101): 1614 - 1616. [Abstract] [PDF]