The bovine renal parathyroid hormone (PTH) receptor has equal affinity for two different amino acid sequences: the receptor binding domains of PTH and PTH-related protein are located within the 14-34 region.
Previous studies examining the interaction of PTH and PTH-related protein (PTHrP) with target tissue have for the most part emphasized the similarity between the two hormones in binding to and activating receptors. This observation that two peptides with limited homology have equal affinities for the same receptor is unusual. In this report we investigated two aspects of PTH/PTHrP-receptor interactions. First, the nonhomologous 14-34 regions of PTH and PTHrP were synthesized and evaluated. Second, hybrid peptides containing the 7-18 fragment of one hormone combined with the 19-34 region of the other hormone were studied to determine whether interactions between these two regions are required for receptor recognition. All four peptides were examined in bovine renal cortical membrane and rat osteosarcoma (ROS 17/2.8) cell PTH-binding and PTH-stimulated adenylate cyclase assays. The results indicate that the receptor-binding domains of PTH and PTHrP lie outside of the 1-13 region, the region containing sequence homology shared by the two hormones, and that two peptides of different amino acid sequence bind with equal affinity to the bovine renal PTH receptor. However, in the absence of the N-terminal region, the rat bone PTH receptor displays a preference for the C-terminal (19-34 sequence) region of PTHrP.
Caulfield
M P
MP
Department of Biological Research and Molecular Biology, Merck, Sharp, and Dohme Research Laboratories, West Point, Pennsylvania 19486.
McKee
R L
RL
Goldman
M E
ME
Duong
L T
LT
Fisher
J E
JE
Gay
C T
CT
DeHaven
P A
PA
Levy
J J
JJ
Roubini
E
E
Nutt
R F
RF
D000262:Adenylyl Cyclases / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002417:Cattle; D000242:Cyclic AMP / Q000096:biosynthesis; D007668:Kidney / Q000378:metabolism*; D008969:Molecular Sequence Data; D012516:Osteosarcoma; D010281:Parathyroid Hormone / Q000378:metabolism* / Q000494:pharmacology; D044162:Parathyroid Hormone-Related Protein; D010446:Peptide Fragments / Q000378:metabolism / Q000494:pharmacology; D011506:Proteins / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D011956:Receptors, Cell Surface / Q000378:metabolism*; D018016:Receptors, Parathyroid Hormone; D014407:Tumor Cells, Cultured
D010281:Parathyroid Hormone; D044162:Parathyroid Hormone-Related Protein; D010446:Peptide Fragments; D011506:Proteins; D011956:Receptors, Cell Surface; D018016:Receptors, Parathyroid Hormone; C064773:parathyroid hormone (14-34)amide, Tyr(34)-; C064820:parathyroid hormone-related protein (14-34) amide; D000242:Cyclic AMP; D000262:Adenylyl Cyclases