THE HUMAN GLUCAGON RECEPTOR ENCODING GENE - STRUCTURE, CDNA SEQUENCE AND CHROMOSOMAL LOCALIZATION

Characterization of the human glucagon-receptor-encoding gene (GGR) sh ould provide a greater understanding of blood glucose regulation and m ay reveal a genetic basis for the pathogenesis of diabetes. A cDNA enc oding a complete functional human glucagon receptor (GGR) was isolated from a liver cDNA library by a combination of polymerase chain reacti on and colony hybridization. The cDNA encodes a receptor protein with 80% identity to rat GGR that binds [I-125]glucagon and transduces a si gnal leading to increases in the concentration of intracellular cyclic adenosine 3',5'-monophosphate. Southern blot analysis of human DNA re veals a hybridization pattern consistent with a single GGR locus. In s itu hybridization to metaphase chromosome preparations maps the GGR lo cus to chromosome 17q25. Analysis of the genomic sequence shows that t he coding region spans over 5.5 kb and is interrupted by 12 introns.