Full activation of chimeric receptors by hybrids between parathyroid hormone and calcitonin. Evidence for a common pattern of ligand-receptor interaction.
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.
Department of Medicine and Children's Service, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA.
C
C
Bergwitz
T J
TJ
Gardella
M R
MR
Flannery
J T
JT
Potts
H M
HM
Kronenberg
S R
SR
Goldring
H
H
Jüppner
D000818:Animals; D019556:COS Cells; D002116:Calcitonin / Q000378:metabolism*; D010281:Parathyroid Hormone / Q000378:metabolism*; D051381:Rats; D018003:Receptors, Calcitonin / Q000378:metabolism*; D018016:Receptors, Parathyroid Hormone / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism
D010281:Parathyroid Hormone; D018003:Receptors, Calcitonin; D018016:Receptors, Parathyroid Hormone; D011993:Recombinant Fusion Proteins; D002116:Calcitonin