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Molecular mapping of epitopes involved in ligand activation of the human receptor for the neuropeptide, VIP, based on hybrids with the human secretin receptor

Olde, Björn LU ; Sabirsh, Alan LU and Owman, Christer LU (1998) In Journal of Molecular Neuroscience 11(2). p.127-134
Abstract
Receptors for the neurotransmitter and neuroendocrine peptides, vasoactive intesinal peptide (VIP) and secretin, both belong to the Type B subfamily of G-protein-coupled receptors. This group is evolutionally as well as structurally distinct from the much larger Type A, or rhodopsin-type, subfamily. We have mapped the ligand-activating epitopes of the human VIP1 receptor by the use of hybrid receptor constructs with the human secretin receptor. Twelve chimeras were synthesized the successively replacing portions of the former receptor with corresponding portions of the latter receptor, or by interchanging the first extracellular loops. Each of the different chimeric receptor DNAs were then expressed in murine reporter cells, and their... (More)
Receptors for the neurotransmitter and neuroendocrine peptides, vasoactive intesinal peptide (VIP) and secretin, both belong to the Type B subfamily of G-protein-coupled receptors. This group is evolutionally as well as structurally distinct from the much larger Type A, or rhodopsin-type, subfamily. We have mapped the ligand-activating epitopes of the human VIP1 receptor by the use of hybrid receptor constructs with the human secretin receptor. Twelve chimeras were synthesized the successively replacing portions of the former receptor with corresponding portions of the latter receptor, or by interchanging the first extracellular loops. Each of the different chimeric receptor DNAs were then expressed in murine reporter cells, and their ability to activate cAMP production was investigated on stimulation with the respective natural peptide ligands. We stimulated the reporter cells with secretion or VIP following transient expression of the receptor chimeras. The experiments indicated that there are two molecular domains of importance for the recognition and activation of these peptides, namely, the inner portion of the extracellular tail and the first extracellular loop of the two receptors. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Molecular Neuroscience
volume
11
issue
2
pages
127 - 134
publisher
Humana Press
external identifiers
  • pmid:10096039
  • scopus:0032469805
ISSN
0895-8696
DOI
10.1385/JMN:11:2:127
language
English
LU publication?
yes
id
f91b613d-e83b-4fc0-8bc4-7cb0b1d23cbb (old id 1113445)
date added to LUP
2008-07-15 10:10:45
date last changed
2017-01-01 07:26:28
@article{f91b613d-e83b-4fc0-8bc4-7cb0b1d23cbb,
  abstract     = {Receptors for the neurotransmitter and neuroendocrine peptides, vasoactive intesinal peptide (VIP) and secretin, both belong to the Type B subfamily of G-protein-coupled receptors. This group is evolutionally as well as structurally distinct from the much larger Type A, or rhodopsin-type, subfamily. We have mapped the ligand-activating epitopes of the human VIP1 receptor by the use of hybrid receptor constructs with the human secretin receptor. Twelve chimeras were synthesized the successively replacing portions of the former receptor with corresponding portions of the latter receptor, or by interchanging the first extracellular loops. Each of the different chimeric receptor DNAs were then expressed in murine reporter cells, and their ability to activate cAMP production was investigated on stimulation with the respective natural peptide ligands. We stimulated the reporter cells with secretion or VIP following transient expression of the receptor chimeras. The experiments indicated that there are two molecular domains of importance for the recognition and activation of these peptides, namely, the inner portion of the extracellular tail and the first extracellular loop of the two receptors.},
  author       = {Olde, Björn and Sabirsh, Alan and Owman, Christer},
  issn         = {0895-8696},
  language     = {eng},
  number       = {2},
  pages        = {127--134},
  publisher    = {Humana Press},
  series       = {Journal of Molecular Neuroscience},
  title        = {Molecular mapping of epitopes involved in ligand activation of the human receptor for the neuropeptide, VIP, based on hybrids with the human secretin receptor},
  url          = {http://dx.doi.org/10.1385/JMN:11:2:127},
  volume       = {11},
  year         = {1998},
}