PUBLICATION
Identification and Characterization of Two Parathyroid Hormone-Like Molecules in Zebrafish
- Authors
- Gensure, R.C., Ponugoti, B., Gunes, Y., Papasani, M.R., Lanske, B., Bastepe, M., Rubin, D.A., and Jüppner, H.
- ID
- ZDB-PUB-040113-4
- Date
- 2004
- Source
- Endocrinology 145(4): 1634-1639 (Journal)
- Registered Authors
- Rubin, David
- Keywords
- none
- MeSH Terms
-
- Amino Acid Sequence
- Animals
- DNA, Complementary
- Evolution, Molecular
- Fishes/genetics
- Genome
- Humans
- Molecular Sequence Data
- Parathyroid Hormone/genetics*
- Parathyroid Hormone/metabolism*
- Peptide Fragments/genetics*
- Peptide Fragments/metabolism*
- Phylogeny
- Receptor, Parathyroid Hormone, Type 1/metabolism
- Receptors, Parathyroid Hormone/metabolism
- Zebrafish/genetics*
- Zebrafish/metabolism*
- PubMed
- 14684608 Full text @ Endocrinology
Citation
Gensure, R.C., Ponugoti, B., Gunes, Y., Papasani, M.R., Lanske, B., Bastepe, M., Rubin, D.A., and Jüppner, H. (2004) Identification and Characterization of Two Parathyroid Hormone-Like Molecules in Zebrafish. Endocrinology. 145(4):1634-1639.
Abstract
Zebrafish (Danio rerio) have receptors homologous to the human PTH/PTHrP receptor (PTH1R) and PTH-2 receptor (PTH2R), and an additional receptor (PTH3R) with high homology to the PTH1R. To find natural ligands for zPTH1R and zPTH3R, we searched the zebrafish genomic database and discovered two distinct regions that, when translated (zPTH1 and zPTH2), showed high homology to human PTH (hPTH). Isolation of cDNAs and determination of the intron/exon boundaries revealed genomic structures which were simliar to known PTHs. Peptides consisting of the first 34 amino acids after the pre- and pro-sequences of the zebrafish PTHs were synthesized and were shown to be fully active at the human PTH1R. zPTH2(1-34) was, however, 30-fold less potent at the zebrafish PTH1R than hPTH(1-34), hPTHrP(1-36) and zPTH1(1-34). When tested with zPTH3R, zPTH1(1-34) and hPTHrP(1-36) showed similar potencies, while the potency of zPTH2(1-34) was moderately (3-fold) reduced. To determine if other fishes have multiple PTHs, we searched the genomic database of the Japanese pufferfish and identified zPTH1 and zPTH2 homologs. Phylogenetic analysis showed that PTHs from zebrafish and pufferfish are more closely related to each other than to known mammalian PTH homologs or to PTHrP and TIP39. This is consistent with evolution of two telost PTH-like peptides occurring after the evolutionary divergence between fishes and mammals. Overall, the PTH system appears more complex in fishes than in mammals, providing evidence of continued evolution in non-tetrapod species. The availability of multiple forms of fish PTH and their receptors provide additional tools for PTH ligand/receptor structure-function studies.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping