This Article Full Text Full Text (PDF) All Versions of this Article: 145/7/3273    most recent Author Manuscript (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Chow, B. K. C. Articles by Mojsov, S. Search for Related Content PubMed PubMed Citation Articles by Chow, B. K. C. Articles by Mojsov, S.

Identification and Characterization of a Glucagon Receptor from the Goldfish Carassius auratus: Implications for the Evolution of the Ligand Specificity of Glucagon Receptors in Vertebrates

Department of Zoology (B.K.C.C., R.L.C.H., C.-M.Y.), University of Hong Kong, Hong Kong; Department of Biology (T.W.M.), University of Ottawa, Ottawa, Ontario, Canada K1N 6N5; Weill Medical College of Cornell University (P.J.C.) and The Rockefeller University (M.M., S.M.), New York, New York 10021-6399

Address all correspondence and requests for reprints to: Svetlana Mojsov, The Rockefeller University, 1230 York Avenue, New York, New York 10021-6399. E-mail: mojsov{at}mail.rockefeller.edu.

The structural basis of ligand selectivity of G protein-coupled receptors for metabolic hormones has been an area of intense investigation, and yet it remains unresolved. One approach to delineating the mechanism of ligand-receptor interactions is to compare the ligand specificities of receptors expressed in species that emerged at different times within vertebrate evolution. In this paper we describe the isolation, functional, and phylogenetic characterization of the glucagon receptor from the goldfish Carassius auratus (Teleostei, order Cypriniformes), and compare its ligand specificity with that of the homologous rat receptor. Goldfish (gf) glucagon stimulated glucose production in a dose-dependent manner from isolated goldfish hepatocytes, resulting in 5-fold increase at 1 µM. The goldfish glucagon receptor (gfGlucR) shares 56, 51, 50, and 52% amino acid identities with frog Rana tigrina regulosa, mouse, rat, and human glucagon receptors, respectively. In competitive binding experiments, the recombinant gfGlucR displays high affinity toward goldfish, zebrafish, and human glucagons (IC₅₀ = 0.6, 9, and 13 nM, respectively) but not toward goldfish glucagon-like peptide-1 or human glucagon-like peptide-1 (7–36) amide. Whereas both goldfish and human glucagons stimulated dose-dependent increases in intracellular cAMP through the recombinant gfGlucR, the recombinant rat GlucR interacted only with human glucagon, analogous to the specificity of the previously characterized glucagon receptor from the frog R. tigrina regulosa. Our results demonstrate that the binding pocket of gfGlucR can accommodate a broad range of glucagon structures and that in the frogs and mammals, there is a structural switch to a more restrictive conformation of glucagon receptors.

This article has been cited by other articles:

				D. M. Irwin and K. Wong Evolution of New Hormone Function: Loss and Gain of a Receptor J. Hered., May 1, 2005; 96(3): 205 - 211. [Abstract] [Full Text] [PDF]