The vasopressin receptor family is unique among all classes of peptide receptors in that its individual members couple to different subsets of G proteins. The V vasopressin receptor, for example, is preferentially linked to G proteins of the G class (biochemical response: stimulation of phosphatidylinositol hydrolysis), whereas the V vasopressin receptor is selectively coupled to G (biochemical response: stimulation of adenylyl cyclase). To elucidate the structural basis underlying this functional heterogeneity, we have systematically exchanged different intracellular domains between the V and V receptors. Transient expression of the resulting hybrid receptors in COS-7 cells showed that all mutant receptors containing V receptor sequence in the second intracellular loop were able to activate the phosphatidylinositol pathway with high efficiency. On the other hand, only those hybrid receptors containing V receptor sequence in the third intracellular loop were capable of efficiently stimulating cAMP production. These findings suggest that the differential G protein coupling profiles of individual members of a structurally closely related receptor subfamily can be determined by different single intracellular receptor domains.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				F. Wunder, A. Rebmann, A. Geerts, and B. Kalthof Pharmacological and Kinetic Characterization of Adrenomedullin 1 and Calcitonin Gene-Related Peptide 1 Receptor Reporter Cell Lines Mol. Pharmacol., April 1, 2008; 73(4): 1235 - 1243. [Abstract] [Full Text] [PDF]

				M. L. Matsumoto, K. Narzinski, G. V. Nikiforovich, and T. J. Baranski A Comprehensive Structure-Function Map of the Intracellular Surface of the Human C5a Receptor: II. ELUCIDATION OF G PROTEIN SPECIFICITY DETERMINANTS J. Biol. Chem., February 2, 2007; 282(5): 3122 - 3133. [Abstract] [Full Text] [PDF]

				M. L. Matsumoto, K. Narzinski, P. D. Kiser, G. V. Nikiforovich, and T. J. Baranski A Comprehensive Structure-Function Map of the Intracellular Surface of the Human C5a Receptor: I. IDENTIFICATION OF CRITICAL RESIDUES J. Biol. Chem., February 2, 2007; 282(5): 3105 - 3121. [Abstract] [Full Text] [PDF]

				N. Wu, R. Macion-Dazard, S. Nithianantham, Z. Xu, S. M. Hanson, S. A. Vishnivetskiy, V. V. Gurevich, M. Thibonnier, and M. Shoham Soluble Mimics of the Cytoplasmic Face of the Human V1-Vascular Vasopressin Receptor Bind Arrestin2 and Calmodulin Mol. Pharmacol., July 1, 2006; 70(1): 249 - 258. [Abstract] [Full Text] [PDF]

				S. R. Hawtin Charged Residues of the Conserved DRY Triplet of the Vasopressin V1a Receptor Provide Molecular Determinants for Cell Surface Delivery and Internalization Mol. Pharmacol., October 1, 2005; 68(4): 1172 - 1182. [Abstract] [Full Text] [PDF]

				S. Acharjee, J.-L. Do-Rego, D. Y. Oh, R. S. Ahn, H. Choe, H. Vaudry, K. Kim, J. Y. Seong, and H. B. Kwon Identification of Amino Acid Residues That Direct Differential Ligand Selectivity of Mammalian and Nonmammalian V1a Type Receptors for Arginine Vasopressin and Vasotocin: INSIGHTS INTO MOLECULAR COEVOLUTION OF V1a TYPE RECEPTORS AND THEIR LIGANDS J. Biol. Chem., December 24, 2004; 279(52): 54445 - 54453. [Abstract] [Full Text] [PDF]

				S. Granier, S. Terrillon, R. Pascal, H. Demene, M. Bouvier, G. Guillon, and C. Mendre A Cyclic Peptide Mimicking the Third Intracellular Loop of the V2 Vasopressin Receptor Inhibits Signaling through Its Interaction with Receptor Dimer and G Protein J. Biol. Chem., December 3, 2004; 279(49): 50904 - 50914. [Abstract] [Full Text] [PDF]

				C. M. Revankar, C. M. Vines, D. F. Cimino, and E. R. Prossnitz Arrestins Block G Protein-coupled Receptor-mediated Apoptosis J. Biol. Chem., June 4, 2004; 279(23): 24578 - 24584. [Abstract] [Full Text] [PDF]

				Y. Sugimoto, T. Nakato, A. Kita, Y. Takahashi, N. Hatae, H. Tabata, S. Tanaka, and A. Ichikawa A Cluster of Aromatic Amino Acids in the i2 Loop Plays a Key Role for Gs Coupling in Prostaglandin EP2 and EP3 Receptors J. Biol. Chem., March 19, 2004; 279(12): 11016 - 11026. [Abstract] [Full Text] [PDF]

				J. ANTUNES-RODRIGUES, M. DE CASTRO, L. L. K. ELIAS, M. M. VALENCA, and S. M. McCANN Neuroendocrine Control of Body Fluid Metabolism Physiol Rev, January 1, 2004; 84(1): 169 - 208. [Abstract] [Full Text] [PDF]

				L. McGrew, R. D. Price, E. Hackler, M. S. S. Chang, and E. Sanders-Bush RNA Editing of the Human Serotonin 5-HT2C Receptor Disrupts Transactivation of the Small G-Protein RhoA Mol. Pharmacol., January 1, 2004; 65(1): 252 - 256. [Abstract] [Full Text] [PDF]

				C. M. Tan, H. H. Nickols, and L. E. Limbird Appropriate Polarization following Pharmacological Rescue of V2 Vasopressin Receptors Encoded by X-linked Nephrogenic Diabetes Insipidus Alleles Involves a Conformation of the Receptor That Also Attains Mature Glycosylation J. Biol. Chem., September 12, 2003; 278(37): 35678 - 35686. [Abstract] [Full Text] [PDF]

				Z. Gaborik, G. Jagadeesh, M. Zhang, A. Spat, K. J. Catt, and L. Hunyady The Role of a Conserved Region of the Second Intracellular Loop in AT1 Angiotensin Receptor Activation and Signaling Endocrinology, June 1, 2003; 144(6): 2220 - 2228. [Abstract] [Full Text] [PDF]

				C.-Y. Lin, M. G. Varma, A. Joubel, S. Madabushi, O. Lichtarge, and D. L. Barber Conserved Motifs in Somatostatin, D2-dopamine, and alpha 2B-Adrenergic Receptors for Inhibiting the Na-H Exchanger, NHE1 J. Biol. Chem., April 18, 2003; 278(17): 15128 - 15135. [Abstract] [Full Text] [PDF]

				M. Yang, W. Wang, M. Zhong, A. Philippi, O. Lichtarge, and B. M. Sanborn Lysine 270 in the Third Intracellular Domain of the Oxytocin Receptor is an Important Determinant for G{alpha}q Coupling Specificity Mol. Endocrinol., April 1, 2002; 16(4): 814 - 823. [Abstract] [Full Text] [PDF]

				M. Thibonnier, C. L. Plesnicher, K. Berrada, and L. Berti-Mattera Role of the human V1 vasopressin receptor COOH terminus in internalization and mitogenic signal transduction Am J Physiol Endocrinol Metab, July 1, 2001; 281(1): E81 - E92. [Abstract] [Full Text] [PDF]

				G. Gimpl and F. Fahrenholz The Oxytocin Receptor System: Structure, Function, and Regulation Physiol Rev, April 1, 2001; 81(2): 629 - 683. [Abstract] [Full Text] [PDF]

				R. D. Price and E. Sanders-Bush RNA Editing of the Human Serotonin 5-HT2C Receptor Delays Agonist-Stimulated Calcium Release Mol. Pharmacol., October 1, 2000; 58(4): 859 - 862. [Abstract] [Full Text]

				H. M. Miettinen, J. M. Gripentrog, M. M. Mason, and A. J. Jesaitis Identification of Putative Sites of Interaction between the Human Formyl Peptide Receptor and G Protein J. Biol. Chem., September 24, 1999; 274(39): 27934 - 27942. [Abstract] [Full Text] [PDF]

				F. Fanelli, P. Barbier, D. Zanchetta, P. G. de Benedetti, and B. Chini Activation Mechanism of Human Oxytocin Receptor: A Combined Study of Experimental and Computer-Simulated Mutagenesis Mol. Pharmacol., July 1, 1999; 56(1): 214 - 225. [Abstract] [Full Text]

				J. C. Rice, J. S. Spence, J. Megyesi, R. M. Goldblum, and R. L. Safirstein Expression of the polymeric immunoglobulin receptor and excretion of secretory IgA in the postischemic kidney Am J Physiol Renal Physiol, May 1, 1999; 276(5): F666 - F673. [Abstract] [Full Text] [PDF]

				R. Vezza, A. Habib, and G. A. FitzGerald Differential Signaling by the Thromboxane Receptor Isoforms via the Novel GTP-binding Protein, Gh J. Biol. Chem., April 30, 1999; 274(18): 12774 - 12779. [Abstract] [Full Text] [PDF]

				I. Erlenbach and J. Wess Molecular Basis of V2 Vasopressin Receptor/Gs Coupling Selectivity J. Biol. Chem., October 9, 1998; 273(41): 26549 - 26558. [Abstract] [Full Text] [PDF]

				M. Waldhoer, E. Bofill-Cardona, G. Milligan, M. Freissmuth, and C. Nanoff Differential Uncoupling of A1 Adenosine and D2 Dopamine Receptors by Suramin and Didemethylated Suramin (NF037) Mol. Pharmacol., May 1, 1998; 53(5): 808 - 818. [Abstract] [Full Text]

				J. C. Rice, J. S. Spence, J. Megyesi, R. L. Safirstein, and R. M. Goldblum Regulation of the polymeric immunoglobulin receptor by water intake and vasopressin in the rat kidney Am J Physiol Renal Physiol, May 1, 1998; 274(5): F966 - F977. [Abstract] [Full Text] [PDF]

				G. Innamorati, H. M. Sadeghi, N. T. Tran, and M. Birnbaumer A serine cluster prevents recycling of the V2 vasopressin receptor PNAS, March 3, 1998; 95(5): 2222 - 2226. [Abstract] [Full Text] [PDF]

				S. A. Carlson, T. K. Chatterjee, K. P. Murphy, and R. A. Fisher Mutation of a Putative Amphipathic alpha -Helix in the Third Intracellular Domain of the Platelet-Activating Factor Receptor Disrupts Receptor/G Protein Coupling and Signaling Mol. Pharmacol., March 1, 1998; 53(3): 451 - 458. [Abstract] [Full Text]

				M. Thibonnier, J. A. Preston, N. Dulin, P. L. Wilkins, L. N. Berti-Mattera, and R. Mattera The Human V3 Pituitary Vasopressin Receptor: Ligand Binding Profile and Density-Dependent Signaling Pathways Endocrinology, October 1, 1997; 138(10): 4109 - 4122. [Abstract] [Full Text] [PDF]

				M. Glass and C. C. Felder Concurrent Stimulation of Cannabinoid CB1 and Dopamine D2 Receptors Augments cAMP Accumulation in Striatal Neurons: Evidence for a Gs Linkage to the CB1 Receptor J. Neurosci., July 15, 1997; 17(14): 5327 - 5333. [Abstract] [Full Text] [PDF]

				H. M. Sadeghi, G. Innamorati, and M. Birnbaumer An X-Linked NDI Mutation Reveals a Requirement for Cell Surface V2R Expression Mol. Endocrinol., June 1, 1997; 11(6): 706 - 713. [Abstract] [Full Text]

				G. Innamorati, H. Sadeghi, A. N. Eberle, and M. Birnbaumer Phosphorylation of the V2 Vasopressin Receptor J. Biol. Chem., January 24, 1997; 272(4): 2486 - 2492. [Abstract] [Full Text] [PDF]

				M. E. Olah and M. E. Olah Identification of A2a Adenosine Receptor Domains Involved in Selective Coupling to GS. ANALYSIS OF CHIMERIC A1/A2a ADENOSINE RECEPTORS J. Biol. Chem., January 3, 1997; 272(1): 337 - 344. [Abstract] [Full Text] [PDF]

				R. Postina, E. Kojro, and F. Fahrenholz Separate Agonist and Peptide Antagonist Binding Sites of the Oxytocin Receptor Defined by Their Transfer into the V2 Vasopressin Receptor J. Biol. Chem., December 6, 1996; 271(49): 31593 - 31601. [Abstract] [Full Text] [PDF]

				M. Kudo, Y. Osuga, B. K. Kobilka, and A. J.W. Hsueh Transmembrane Regions V and VI of the Human Luteinizing Hormone Receptor Are Required for Constitutive Activation by a Mutation in the Third Intracellular Loop J. Biol. Chem., September 13, 1996; 271(37): 22470 - 22478. [Abstract] [Full Text] [PDF]

				T. Yamashita, A. Terakita, and Y. Shichida Distinct Roles of the Second and Third Cytoplasmic Loops of Bovine Rhodopsin in G Protein Activation J. Biol. Chem., October 27, 2000; 275(44): 34272 - 34279. [Abstract] [Full Text] [PDF]

				G. Innamorati, C. Le Gouill, M. Balamotis, and M. Birnbaumer The Long and the Short Cycle. ALTERNATIVE INTRACELLULAR ROUTES FOR TRAFFICKING OF G-PROTEIN-COUPLED RECEPTORS J. Biol. Chem., April 13, 2001; 276(16): 13096 - 13103. [Abstract] [Full Text] [PDF]

				R. D. Price, D. M. Weiner, M. S. S. Chang, and E. Sanders-Bush RNA Editing of the Human Serotonin 5-HT2C Receptor Alters Receptor-mediated Activation of G13 Protein J. Biol. Chem., November 21, 2001; 276(48): 44663 - 44668. [Abstract] [Full Text] [PDF]