ZFIN ID: ZDB-PUB-990824-48
A G protein-coupled receptor from zebrafish is activated by human parathyroid hormone and not by human or teleost parathyroid hormone-related peptide. Implications for the evolutionary conservation of calcium-regulating peptide hormones
Rubin, D.A., Hellman, P., Zon, L.I., Lobb, C.J., Bergwitz, C., and Juppner, H.
Date: 1999
Source: The Journal of biological chemistry   274(33): 23035-23042 (Journal)
Registered Authors: Rubin, David, Zon, Leonard I.
Keywords: none
MeSH Terms:
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Biological Evolution*
  • Blotting, Southern
  • Cloning, Molecular
  • DNA Probes
  • DNA, Complementary
  • GTP-Binding Proteins/metabolism*
  • Humans
  • Ictaluridae
  • Molecular Sequence Data
  • Parathyroid Hormone/genetics
  • Parathyroid Hormone/metabolism*
  • Parathyroid Hormone-Related Protein
  • Proteins/genetics
  • Proteins/metabolism*
  • RNA Splicing
  • Rats
  • Receptor, Parathyroid Hormone, Type 2
  • Receptors, Parathyroid Hormone/metabolism*
  • Sequence Homology, Amino Acid
  • Zebrafish
PubMed: 10438471 Full text @ J. Biol. Chem.
Genomic and cDNA clones encoding portions of a putative catfish parathyroid hormone (PTH) 2 receptor (PTH2R) led to the isolation of a cDNA encoding a full-length zebrafish PTH2R (zPTH2R). The zPTH2R shared 63 and 60% amino acid sequence identity with human and rat PTH2Rs, respectively, 47-52% identity with mammalian and frog PTH/PTHrP receptors (PTH1R), and less than 37% with other members of this family of G protein-coupled receptors. COS-7 cells expressing zPTH2R(43), a 5' splice variant that lacked 17 amino acids in the amino-terminal extracellular domain, showed cAMP accumulation when challenged with [Tyr(34)]hPTH(1-34)-amide (hPTH) (EC(50), 1.64 +/- 0. 95 nM) and [Ile(5),Trp(23),Tyr(36)]hPTHrP-(1-36)-amide ([Ile(5), Trp(23)]hPTHrP) (EC(50), 46.8 +/- 12.1 nM) but not when stimulated with [Tyr(36)]hPTHrP-(1-36)-amide (hPTHrP), [Trp(23), Tyr(36)]hPTHrP-(1-36)-amide ([Trp(23)]hPTHrP), or [Ala(29),Glu(30), Ala(34),Glu(35),Tyr(36)]fugufish PTHrP-(1-36)amide (fuguPTHrP). FuguPTHrP also failed to activate the human PTH2R but had similar efficiency and efficacy as hPTH and hPTHrP when tested with cells expressing the human PTH1R. Agonist-dependent activation of zPTH2R was less efficient than that of zPTH2R(43), and both receptor variants showed no cAMP accumulation when stimulated with either secretin, growth hormone-releasing hormone, or calcitonin. The zPTH2R thus has ligand specificity similar to that of the human homolog, which raises the possibility that a PTH-like molecule exists in zebrafish, species which lack parathyroid glands.