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Functional properties of a synthetic chicken parathyroid hormone-related protein 1-36 fragment.

Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research (1994-07-01)
D T Schermer, M S Bradley, T H Bambino, R A Nissenson, G J Strewler
ABSTRACT

The biologic activities of human parathyroid hormone-related protein [hPTHrP(1-34] and bovine PTH [bPTH(1-34)] are remarkably similar despite marked sequence divergence in their primary binding domain, residues 25-34. Chicken PTHrP (cPTHrP) is identical to hPTHrP through residue 21. However, in the 25-34 region, cPTHrP displays three fewer basic residues than hPTHrP and contains five residues not present in any other member of the PTH/PTHrP family. To assess the biologic consequences of these structural differences, we compared the activities of synthetic [36Tyr]cPTHrP(1-36)NH2 and hPTHrP(1-34)NH2 with those of bPTH(1-34) in avian systems (chicken renal plasma membranes and 19 day chick embryonic bone cells) and mammalian systems [canine renal plasma membranes and rat osteosarcoma cells (UMR-106-H5)]. In both avian and mammalian systems the binding affinity of [36Tyr]cPTHrP(1-36)NH2 (0.8-3.4 nM) was approximately one-half that of hPTHrP(1-34)NH2 (0.4-1.1 nM). The potencies of [36Tyr]cPTHrP(1-36)NH2 and hPTHrP(1-34)NH2 for activation of adenylate cyclase were similar in canine renal membranes (5.2 and 6.7 nM) and chick bone cells (1.0 nM). In UMR-106 cells and chicken renal membranes the potency of [36Tyr[cPTHrP(1-36)NH2 for activation of adenylate cyclase was about one-half that of [36Tyr]hPTHrP(1-36)NH2. Binding of 125I-[36Tyr]cPTHrP(1-36)NH2 to chick bone cells and chicken renal membranes was completely displaced by bPTH(1-34) and hPTHrP(1-34)NH2: thus there was no evidence for a distinct chicken PTHrP receptor. In general, [36Tyr]cPTHrP(1-36)NH2 and hPTHrP(1-34)NH2 activated adenylate cyclase similarly despite their sequence differences in the 25-32 region.(ABSTRACT TRUNCATED AT 250 WORDS)

MATERIALS
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Brand
Product Description

Sigma-Aldrich
Parathyroid Hormone Fragment 1-34 bovine, ≥97% (HPLC), powder