Molecular cloning and characterization of a parathyroid hormone/parathyroid hormone-related peptide receptor: a member of an ancient family of G protein-coupled receptors.
The parathyroid hormone (PTH)/parathyroid hormone-related peptide (PTHrP) receptor belongs to a newly discovered family of G protein-coupled receptors. Members of this family, which have been isolated from mammals, include the receptors for PTH/PTHrP, calcitonin, secretin, growth hormone-releasing hormone, vasoactive intestinal polypeptide (types 1 and 2), gastric-inhibitory polypeptide, glucagon-like peptide 1, glucagon, corticotropin-releasing factor, and the pituitary adenylate cyclase-activating peptide. Very recently, a receptor with remarkable homology to these mammalian receptors was isolated from the insect Manduca sexta, which indicates considerable conservation of these related proteins during evolution. Thus far the cognate ligands for these receptors are 27- to 46-amino-acid residues in length. Members of this novel receptor family are characterized by seven membrane-spanning domains and at least two conserved sites for N-linked glycosylation. Furthermore, 48-amino-acid residues, including eight extracellular cysteines, are identical in all receptors, and many other residues are highly conserved. The PTH/PTHrP receptor is expressed in a large variety of fetal and adult tissues, binds two ligands (PTH and PTHrP) with high affinity, and activates at least two second-messenger systems (adenylate cyclase and phospholipase C).
Jüppner
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Endocrine Unit, Massachusetts General Hospital, Boston 02114.
D000595:Amino Acid Sequence; D000818:Animals; D003001:Cloning, Molecular; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D010281:Parathyroid Hormone / Q000502:physiology; D044162:Parathyroid Hormone-Related Protein; D011506:Proteins / Q000378:metabolism* / Q000502:physiology; D044168:Receptor, Parathyroid Hormone, Type 1; D018016:Receptors, Parathyroid Hormone / Q000737:chemistry / Q000502:physiology*
C470121:PTHLH protein, human; D010281:Parathyroid Hormone; D044162:Parathyroid Hormone-Related Protein; D011506:Proteins; D044168:Receptor, Parathyroid Hormone, Type 1; D018016:Receptors, Parathyroid Hormone; D019204:GTP-Binding Proteins