PUBLICATION
Newly-identified receptors for PHI and GHRH-like peptide in zebrafish help to elucidate the mammalian secretin superfamily
- Authors
- Wu, S., Roch, G., Cervini, L., Rivier, J., and Sherwood, N.
- ID
- ZDB-PUB-080902-28
- Date
- 2008
- Source
- Journal of molecular endocrinology 41(5): 343-366 (Journal)
- Registered Authors
- Sherwood, Nancy M.
- Keywords
- none
- MeSH Terms
-
- Amino Acid Sequence
- Animals
- Base Sequence
- Growth Hormone-Releasing Hormone/genetics
- Growth Hormone-Releasing Hormone/metabolism*
- Humans
- Molecular Sequence Data
- Peptide PHI/genetics
- Peptide PHI/metabolism*
- Peptides/genetics
- Peptides/metabolism
- Phylogeny
- Receptors, Cell Surface/classification
- Receptors, Cell Surface/genetics
- Receptors, Cell Surface/metabolism*
- Secretin/classification
- Secretin/genetics
- Secretin/metabolism*
- Sequence Alignment
- Tissue Distribution
- Zebrafish/genetics
- Zebrafish/metabolism*
- Zebrafish Proteins/classification
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- PubMed
- 18757498 Full text @ J. Mol. Endocrinol.
Citation
Wu, S., Roch, G., Cervini, L., Rivier, J., and Sherwood, N. (2008) Newly-identified receptors for PHI and GHRH-like peptide in zebrafish help to elucidate the mammalian secretin superfamily. Journal of molecular endocrinology. 41(5):343-366.
Abstract
A group of ten hormones in humans are structurally related and known as the secretin superfamily. These hormones bind to G-protein-coupled receptors that activate the cAMP pathway and are clustered as the secretin or B family. We used molecular techniques to clone two full length receptor cDNAs in zebrafish, which were analyzed for amino acid sequence and ligand-binding motifs, phylogenetic position, synteny, tissue expression, functional response, and signaling pathway. Evidence is provided that the two cDNAs are the peptide histidine-isoleucine (PHI) receptor and PRP receptor, which is known as growth hormone-releasing hormone-like peptide (GHRH-LP) receptor in non-mammals. Further we cloned a zebrafish cDNA encoding the peptides PHI and vasoactive intestinal peptide (VIP). The PHI-R cDNA, transfected into COS7 cells, responded to zebrafish PHI in a sensitive and dose-dependent manner (EC50 = 1.8 X 10-9M) but not to PACAP and VIP. The GHRH-LP receptor responded to both zebrafish GHRH-LP1 and GHRH with a 3.5 fold greater response to the former. For comparison, two zebrafish receptors (PAC1 & VPAC1) and two human receptors (VPAC2 & GHRH) were tested with human and/or zebrafish peptides. Unexpectedly, zebrafish VIP activated its PAC1 receptor suggesting that in evolution, PAC1 is not always a specific receptor for PACAP. We conclude that zebrafish, like goldfish, have a specific receptor for PHI and GHRH-LP. Our evidence that zebrafish PHI is more potent than human PHM in activating the human VPAC2 receptor (EC50 = 7.4 X 10-9M) supports our suggestion that the VPAC2R and PHI-R shared a common ancestral receptor.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping