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(Received for publication, June 25, 1996, and in revised form, August 28, 1996)
From the Endocrine Unit and Arthritis Unit, Department of Medicine
and Children's Service, Massachusetts General Hospital and Harvard
Medical School, Boston, Massachusetts 02114
Calcitonin (CT) and parathyroid hormone (PTH),
whose receptors belong to the same family of G protein-coupled
receptors, share no amino acid sequence homology and selectively
activate either CT or PTH receptors. We now show, however, that
reciprocal hybrid ligands (CT/PTH and PTH/CT), which do not activate
the ``wild-type'' receptors, activate PTH/CT and CT/PTH receptor
chimeras, respectively. Our findings indicate that PTH and CT share a
similar architecture with at least two functional, receptor-specific
domains. These domains are sufficiently independent to permit synthetic
hybrid ligands to efficiently activate appropriate receptor chimeras.
Therefore, both ligands follow, despite their very different primary
sequences, a common pattern of ligand-receptor interaction.
Volume 271, Number 43,
Issue of October 25, 1996
pp. 26469-26472
©1996 by The American Society for Biochemistry and Molecular Biology, Inc.
COMMUNICATION:
EVIDENCE FOR A COMMON PATTERN OF LIGAND-RECEPTOR
INTERACTION
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