Functional studies of a glucagon receptor isolated from frog Rana tigrina rugulosa: implications on the molecular evolution of glucagon receptors in vertebrates
| Autor: | Yang Wei, Svetlana Mojsov, Billy K. C. Chow, Elly Sau-Wai Ngan, Dicky L.Y. Tse, Xixuan Du, Lillian Shuk-Nga Chow |
|---|---|
| Jazyk: | angličtina |
| Předmět: |
Ranidae
Biochemistry 0302 clinical medicine Structural Biology Cricetinae Cyclic AMP Receptors Glucagon Receptor Zebrafish 0303 health sciences Recombinant Proteins COS Cells Vertebrates Pituitary Adenylate Cyclase-Activating Polypeptide Glucagon receptor family Frog Vasoactive Intestinal Peptide Amphibian medicine.medical_specialty endocrine system Molecular Sequence Data Biophysics 030209 endocrinology & metabolism CHO Cells Biology Binding Competitive Glucagon Glucagon receptor Evolution Molecular Inhibitory Concentration 50 03 medical and health sciences Secretin Species Specificity Internal medicine biology.animal Genetics medicine Animals Humans Amino Acid Sequence Protein Precursors Molecular Biology Glucagon-like peptide 1 Glucagon-like peptide 1 receptor 030304 developmental biology Messenger RNA Sequence Homology Amino Acid Venoms Neuropeptides Cell Biology biology.organism_classification Peptide Fragments Glucagon antagonist des-His1-[Nle9-Ala11-Ala16] Endocrinology Exenatide Peptides |
| Zdroj: | FEBS Letters. (3):499-504 |
| ISSN: | 0014-5793 |
| DOI: | 10.1016/S0014-5793(99)01112-6 |
| Popis: | In this report, the first amphibian glucagon receptor (GluR) cDNA was characterized from the liver of the frog Rana tigrina rugulosa. Functional expression of the frog GluR in CHO and COS-7 cells showed a high specificity of the receptor towards human glucagon with an EC(50) value of 0.8+/-0.5 nM. The binding of radioiodinated human glucagon to GluR was displaced in a dose-dependent manner only with human glucagon and its antagonist (des-His(1)-[Nle(9)-Ala(11)-Ala(16)]) with IC(50) values of 12.0+/-3. 0 and 7.8+/-1.0 nM, respectively. The frog GluR did not display any affinity towards fish and human GLP-1s, and towards glucagon peptides derived from two species of teleost fishes (goldfish, zebrafish). These fish glucagons contain substitutions in several key residues that were previously shown to be critical for the binding of human glucagon to its receptor. By RT-PCR, mRNA transcripts of frog GluR were located in the liver, brain, small intestine and colon. These results demonstrate a conservation of the functional characteristics of the GluRs in frog and mammalian species and provide a framework for a better understanding of the molecular evolution of the GluR and its physiological function in vertebrates. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|