Document Detail


Identification of binding domains of the growth hormone-releasing hormone receptor by analysis of mutant and chimeric receptor proteins.
MedLine Citation:
PMID:  9605937     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The hypothalamic peptide GH-releasing hormone (GHRH) stimulates the release of GH from the pituitary through binding and activation of the GHRH receptor, which belongs to the family of G protein-coupled receptors. The objective of this study was to identify regions of the receptor critical for interaction with the ligand by expressing and analyzing truncated and chimeric epitope-tagged GHRH receptors. Two truncated receptors, GHRHdeltaN, in which part of the N-terminal domain between the putative signal sequence and the first transmembrane domain was deleted, and GHRHdeltaC, which was truncated downstream of the first intracellular loop, were generated. Both the receptors were deficient in ligand binding, indicating that neither the N-terminal extracellular domain (N terminus) nor the membrane-spanning domains with the associated extracellular loops (C terminus) are alone sufficient for interaction with GHRH. In subsequent studies, chimeric proteins between the receptors for GHRH and vasoactive intestinal peptide (VIP) or secretin were generated, using the predicted start of the first transmembrane domain as the junction for the exchange of the N terminus between receptors. The chimeras having the N terminus of the GHRH receptor and the C terminus of either the VIP or secretin receptor (GNVC and GNSC) did not bind GHRH or activate adenylate cyclase after GHRH treatment. The reciprocal chimeras having the N terminus of either the VIP or secretin receptors and the C terminus of the GHRH receptor (VNGC and SNGC) bound GHRH and stimulated cAMP accumulation after GHRH treatment. These results suggest that although the N-terminal extracellular domain is essential for ligand binding, the transmembrane domains and associated extracellular loop regions of the GHRH receptor provide critical information necessary for specific interaction with GHRH.
Authors:
V I DeAlmeida; K E Mayo
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Molecular endocrinology (Baltimore, Md.)     Volume:  12     ISSN:  0888-8809     ISO Abbreviation:  Mol. Endocrinol.     Publication Date:  1998 May 
Date Detail:
Created Date:  1998-09-23     Completed Date:  1998-09-23     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  8801431     Medline TA:  Mol Endocrinol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  750-65     Citation Subset:  IM    
Affiliation:
Department of Biochemistry, Molecular Biology and Cell Biology, Northwestern University, Evanston, Illinois 60208, USA.
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MeSH Terms
Descriptor/Qualifier:
Antigens, Viral / genetics
Binding Sites / genetics
Epitopes / genetics
Hela Cells
Hemagglutinin Glycoproteins, Influenza Virus / genetics
Humans
Ligands
Models, Molecular
Mutagenesis, Site-Directed*
Protein Binding / genetics
Protein Structure, Tertiary
Receptors, G-Protein-Coupled
Receptors, Gastrointestinal Hormone / analysis,  biosynthesis,  genetics
Receptors, Neuropeptide / analysis,  genetics*,  metabolism*
Receptors, Pituitary Hormone-Regulating Hormone / analysis,  genetics*,  metabolism*
Receptors, Vasoactive Intestinal Peptide / analysis,  biosynthesis,  genetics
Recombinant Fusion Proteins / analysis,  biosynthesis,  metabolism*
Secretin / metabolism
Grant Support
ID/Acronym/Agency:
DK-48071/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Antigens, Viral; 0/Epitopes; 0/Hemagglutinin Glycoproteins, Influenza Virus; 0/Ligands; 0/Receptors, G-Protein-Coupled; 0/Receptors, Gastrointestinal Hormone; 0/Receptors, Neuropeptide; 0/Receptors, Pituitary Hormone-Regulating Hormone; 0/Receptors, Vasoactive Intestinal Peptide; 0/Recombinant Fusion Proteins; 0/secretin receptor; 0/somatotropin releasing hormone receptor; 1393-25-5/Secretin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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