Expression cloning of a common receptor for parathyroid hormone and parathyroid hormone-related peptide from rat osteoblast-like cells: a single receptor stimulates intracellular accumulation of both cAMP and inositol trisphosphates and increases intracellular free calcium.
Parathyroid hormone (PTH), a major regulator of mineral ion metabolism, and PTH-related peptide (PTHrP), which causes hypercalcemia in some cancer patients, stimulate multiple signals (cAMP, inositol phosphates, and calcium) probably by activating common receptors in bone and kidney. Using expression cloning, we have isolated a cDNA clone encoding rat bone PTH/PTHrP receptor from rat osteosarcoma (ROS 17/2.8) cells. The rat bone PTH/PTHrP receptor is 78% identical to the opossum kidney receptor; this identity indicates striking conservation of this receptor across distant mammalian species. Additionally, the rat bone PTH/PTHrP receptor has significant homology to the secretin and calcitonin receptors but not to any other G protein-linked receptor. When expressed in COS cells, a single cDNA clone, expressing either rat bone or opossum kidney PTH/PTHrP receptor, mediates PTH and PTHrP stimulation of both adenylate cyclase and phospholipase C. These properties could explain the diversity of PTH action without the need to postulate other receptor subtypes.
Abou-Samra
A B
AB
Endocrine Unit, Massachusetts General Hospital/Harvard Medical School, Boston 02114.
Jüppner
H
H
Force
T
T
Freeman
M W
MW
Kong
X F
XF
Schipani
E
E
Urena
P
P
Richards
J
J
Bonventre
J V
JV
Potts
J T
JT
D000595:Amino Acid Sequence; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D003001:Cloning, Molecular; D000242:Cyclic AMP / Q000378:metabolism*; D004789:Enzyme Activation; D066298:In Vitro Techniques; D007295:Inositol Phosphates / Q000378:metabolism*; D008969:Molecular Sequence Data; D010006:Osteoblasts / Q000502:physiology; D010281:Parathyroid Hormone / Q000502:physiology*; D044162:Parathyroid Hormone-Related Protein; D011506:Proteins / Q000378:metabolism*; D051381:Rats; D011956:Receptors, Cell Surface / Q000502:physiology*; D018016:Receptors, Parathyroid Hormone; D016415:Sequence Alignment; D015398:Signal Transduction; D014161:Transduction, Genetic; D010738:Type C Phospholipases / Q000502:physiology
D007295:Inositol Phosphates; D010281:Parathyroid Hormone; D044162:Parathyroid Hormone-Related Protein; D011506:Proteins; D011956:Receptors, Cell Surface; D018016:Receptors, Parathyroid Hormone; D000242:Cyclic AMP; D010738:Type C Phospholipases; D002118:Calcium