Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
13
pubmed:dateCreated
1995-5-10
pubmed:abstractText
The binding of glucagon to its hepatic receptor triggers a G-protein-mediated signal that ultimately leads to an increase in hepatic glucose production (gluconeogenesis) and glycogen breakdown (glycogenolysis). In order to elucidate the structural domain(s) of the human glucagon receptor (hGR) involved in the selective binding of glucagon, a series of chimeras was constructed in which various domains of the hGR were replaced by homologous regions from the receptor for the glucoincretin hormone, glucagon-like peptide I (GLP-IR). hGR and GLP-IR are quite similar (47% amino acid identify) yet have readily distinguishable ligand binding characteristics; glucagon binds to the recombinant hGR expressed in COS-7 cells with a Kd that is 1000-fold lower than the Kd for glucagon binding to GLP-IR. In the present study, chimeric receptors were transiently expressed in COS-7 cells and analyzed for glucagon binding. Expression of each receptor chimera was confirmed by immunofluorescence staining using a hGR-specific monoclonal antibody. This report identifies several non-contiguous domains of the hGR that are important for high affinity glucagon binding. Most notable are the membrane-proximal half of the amino-terminal extension, the first extracellular loop, and the third, fourth, and sixth transmembrane domains.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
31
pubmed:volume
270
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
7474-8
pubmed:dateRevised
2005-11-17
pubmed:meshHeading
pubmed-meshheading:7706293-Amino Acid Sequence, pubmed-meshheading:7706293-Animals, pubmed-meshheading:7706293-Cell Line, pubmed-meshheading:7706293-Cercopithecus aethiops, pubmed-meshheading:7706293-Cloning, Molecular, pubmed-meshheading:7706293-Fluorescent Antibody Technique, pubmed-meshheading:7706293-Glucagon, pubmed-meshheading:7706293-Humans, pubmed-meshheading:7706293-Kidney, pubmed-meshheading:7706293-Ligands, pubmed-meshheading:7706293-Liver, pubmed-meshheading:7706293-Molecular Sequence Data, pubmed-meshheading:7706293-Polymerase Chain Reaction, pubmed-meshheading:7706293-Protein Structure, Secondary, pubmed-meshheading:7706293-Receptors, Glucagon, pubmed-meshheading:7706293-Recombinant Fusion Proteins, pubmed-meshheading:7706293-Substrate Specificity, pubmed-meshheading:7706293-Transfection
pubmed:year
1995
pubmed:articleTitle
Glucagon.glucagon-like peptide I receptor chimeras reveal domains that determine specificity of glucagon binding.
pubmed:affiliation
Institute for Metabolic Disorders, Miles, Inc., West Haven, Connecticut 06516, USA.
pubmed:publicationType
Journal Article