Parathyroid hormone 1 receptor

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Parathyroid hormone 1 receptor
PDB 1bl1 EBI.jpg
Rendering of 1BL1
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols PTH1R ; PFE; PTHR; PTHR1
External IDs OMIM168468 MGI97801 HomoloGene267 IUPHAR: PTH1 ChEMBL: 1793 GeneCards: PTH1R Gene
RNA expression pattern
PBB GE PTHR1 205911 at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 5745 19228
Ensembl ENSG00000160801 ENSMUSG00000032492
UniProt Q03431 P41593
RefSeq (mRNA) NM_000316 NM_001083935
RefSeq (protein) NP_000307 NP_001077404
Location (UCSC) Chr 3:
46.92 – 46.95 Mb
Chr 9:
110.72 – 110.74 Mb
PubMed search [1] [2]

Parathyroid hormone/parathyroid hormone-related peptide receptor also known as parathyroid hormone 1 receptor (PTH1R) is a protein that in humans is encoded by the PTH1R gene. PTH1R functions as a receptor for parathyroid hormone (PTH) and for parathyroid hormone-related protein (PTHrP), also called parathyroid hormone-like hormone (PTHLH).

Function[edit]

This "classical" PTH receptor is expressed in high levels in bone and kidney and regulates calcium ion homeostasis through activation of adenylate cyclase and phospholipase C.[1][2] In bone, it is expressed on the surface of osteoblasts. When the receptor is activated through PTH binding, osteoblasts express RANKL (Receptor Activator of Nuclear Factor kB Ligand), which binds to RANK (Receptor Activator of Nuclear Factor kB) on osteoclasts. This turns on osteoclasts to ultimately increase the resorption rate.

Mechanism[edit]

It is a member of the secretin family of G protein-coupled receptors. The activity of this receptor is mediated by Gs G proteins which activate adenylyl cyclase. Besides, they also activate phosphatidylinositol-calcium second messenger system.

Pathology[edit]

Defects in this receptor are known to be the cause of Jansen's metaphyseal chondrodysplasia (JMC), chondrodysplasia Blomstrand type (BOCD), as well as enchondromatosis [3] and primary failure of tooth eruption. [4]

Interactions[edit]

Parathyroid hormone 1 receptor has been shown to interact with Sodium-hydrogen exchange regulatory cofactor 2[5] and Sodium-hydrogen antiporter 3 regulator 1.[5]

See also[edit]

References[edit]

  1. ^ Mannstadt M, Jüppner H, Gardella TJ (1999). "Receptors for PTH and PTHrP: their biological importance and functional properties". Am. J. Physiol. 277 (5 Pt 2): F665–75. PMID 10564229. 
  2. ^ Offermanns S, Iida-Klein A, Segre GV, Simon MI (1996). "G alpha q family members couple parathyroid hormone (PTH)/PTH-related peptide and calcitonin receptors to phospholipase C in COS-7 cells". Mol. Endocrinol. 10 (5): 566–74. doi:10.1210/me.10.5.566. PMID 8732687. 
  3. ^ "Entrez Gene: PTH1R parathyroid hormone 1 receptor". 
  4. ^ Yamaguchi, T; Hosomichi, K; Narita, A; Shirota, T; Tomoyasu, Y; Maki, K; Inoue, I (Mar 14, 2011). "Exome resequencing combined with linkage analysis identifies novel PTH1R variants in primary failure of tooth eruption in Japanese.". Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 26 (7): 1655–61. doi:10.1002/jbmr.385. PMID 21404329. 
  5. ^ a b Mahon, Matthew J; Donowitz Mark; Yun C Chris; Segre Gino V (Jun 2002). "Na(+)/H(+ ) exchanger regulatory factor 2 directs parathyroid hormone 1 receptor signalling". Nature (England) 417 (6891): 858–61. doi:10.1038/nature00816. ISSN 0028-0836. PMID 12075354. 

Further reading[edit]

  • Pioszak A, Harikumar K, Parker, N "et al." (2010). "Dimeric arrangement of the parathyroid hormone receptor and a structural mechanism for ligand-induced dissociation.". J. Biol Chem. 285 (16): 12435–44. doi:10.1074/jbc.M109.093138. PMID 20172855. 
  • Bonaventure J, Silve C (2006). "[Hereditary skeletal dysplasias and FGFR3 and PTHR1 signaling pathways]". Med Sci (Paris) 21 (11): 954–61. doi:10.1051/medsci/20052111954. PMID 16274647. 
  • Dawson SJ, White LA (1992). "Treatment of Haemophilus aphrophilus endocarditis with ciprofloxacin.". J. Infect. 24 (3): 317–20. doi:10.1016/S0163-4453(05)80037-4. PMID 1602151. 
  • Schipani E, Kruse K, Jüppner H (1995). "A constitutively active mutant PTH-PTHrP receptor in Jansen-type metaphyseal chondrodysplasia.". Science 268 (5207): 98–100. doi:10.1126/science.7701349. PMID 7701349. 
  • Schipani E, Weinstein LS, Bergwitz C, et al. (1995). "Pseudohypoparathyroidism type Ib is not caused by mutations in the coding exons of the human parathyroid hormone (PTH)/PTH-related peptide receptor gene.". J. Clin. Endocrinol. Metab. 80 (5): 1611–21. doi:10.1210/jc.80.5.1611. PMID 7745008. 
  • Pausova Z, Bourdon J, Clayton D, et al. (1994). "Cloning of a parathyroid hormone/parathyroid hormone-related peptide receptor (PTHR) cDNA from a rat osteosarcoma (UMR 106) cell line: chromosomal assignment of the gene in the human, mouse, and rat genomes.". Genomics 20 (1): 20–6. doi:10.1006/geno.1994.1122. PMID 8020952. 
  • McCuaig KA, Clarke JC, White JH (1994). "Molecular cloning of the gene encoding the mouse parathyroid hormone/parathyroid hormone-related peptide receptor.". Proc. Natl. Acad. Sci. U.S.A. 91 (11): 5051–5. doi:10.1073/pnas.91.11.5051. PMID 8197183. 
  • Schipani E, Karga H, Karaplis AC, et al. (1993). "Identical complementary deoxyribonucleic acids encode a human renal and bone parathyroid hormone (PTH)/PTH-related peptide receptor.". Endocrinology 132 (5): 2157–65. doi:10.1210/en.132.5.2157. PMID 8386612. 
  • Schneider H, Feyen JH, Seuwen K, Movva NR (1993). "Cloning and functional expression of a human parathyroid hormone receptor.". Eur. J. Pharmacol. 246 (2): 149–55. doi:10.1016/0922-4106(93)90092-N. PMID 8397094. 
  • Schipani E, Langman CB, Parfitt AM, et al. (1996). "Constitutively activated receptors for parathyroid hormone and parathyroid hormone-related peptide in Jansen's metaphyseal chondrodysplasia.". N. Engl. J. Med. 335 (10): 708–14. doi:10.1056/NEJM199609053351004. PMID 8703170. 
  • Zhou AT, Bessalle R, Bisello A, et al. (1997). "Direct mapping of an agonist-binding domain within the parathyroid hormone/parathyroid hormone-related protein receptor by photoaffinity crosslinking.". Proc. Natl. Acad. Sci. U.S.A. 94 (8): 3644–9. doi:10.1073/pnas.94.8.3644. PMID 9108031. 
  • Schipani E, Jensen GS, Pincus J, et al. (1997). "Constitutive activation of the cyclic adenosine 3',5'-monophosphate signaling pathway by parathyroid hormone (PTH)/PTH-related peptide receptors mutated at the two loci for Jansen's metaphyseal chondrodysplasia.". Mol. Endocrinol. 11 (7): 851–8. doi:10.1210/me.11.7.851. PMID 9178745. 
  • Jobert AS, Zhang P, Couvineau A, et al. (1998). "Absence of functional receptors for parathyroid hormone and parathyroid hormone-related peptide in Blomstrand chondrodysplasia.". J. Clin. Invest. 102 (1): 34–40. doi:10.1172/JCI2918. PMID 9649554. 
  • Pellegrini M, Bisello A, Rosenblatt M, et al. (1998). "Binding domain of human parathyroid hormone receptor: from conformation to function.". Biochemistry 37 (37): 12737–43. doi:10.1021/bi981265h. PMID 9737850. 
  • Zhang P, Jobert AS, Couvineau A, Silve C (1998). "A homozygous inactivating mutation in the parathyroid hormone/parathyroid hormone-related peptide receptor causing Blomstrand chondrodysplasia.". J. Clin. Endocrinol. Metab. 83 (9): 3365–8. doi:10.1210/jc.83.9.3373. PMID 9745456. 
  • Adams AE, Bisello A, Chorev M, et al. (1999). "Arginine 186 in the extracellular N-terminal region of the human parathyroid hormone 1 receptor is essential for contact with position 13 of the hormone.". Mol. Endocrinol. 12 (11): 1673–83. doi:10.1210/me.12.11.1673. PMID 9817594. 
  • Matsuzaki K, Katayama K, Takahashi Y, et al. (1999). "Human osteoclast-like cells are formed from peripheral blood mononuclear cells in a coculture with SaOS-2 cells transfected with the parathyroid hormone (PTH)/PTH-related protein receptor gene.". Endocrinology 140 (2): 925–32. doi:10.1210/en.140.2.925. PMID 9927325. 
  • Schipani E, Langman C, Hunzelman J, et al. (1999). "A novel parathyroid hormone (PTH)/PTH-related peptide receptor mutation in Jansen's metaphyseal chondrodysplasia.". J. Clin. Endocrinol. Metab. 84 (9): 3052–7. doi:10.1210/jc.84.9.3052. PMID 10487664. 
  • Karperien M, van der Harten HJ, van Schooten R, et al. (1999). "A frame-shift mutation in the type I parathyroid hormone (PTH)/PTH-related peptide receptor causing Blomstrand lethal osteochondrodysplasia.". J. Clin. Endocrinol. Metab. 84 (10): 3713–20. doi:10.1210/jc.84.10.3713. PMID 10523019. 
  • Watson PH, Fraher LJ, Natale BV, et al. (2000). "Nuclear localization of the type 1 parathyroid hormone/parathyroid hormone-related peptide receptor in MC3T3-E1 cells: association with serum-induced cell proliferation.". Bone 26 (3): 221–5. doi:10.1016/S8756-3282(99)00264-1. PMID 10709993. 
  • Truneh A, Sharma S, Silverman C, et al. (2000). "Temperature-sensitive differential affinity of TRAIL for its receptors. DR5 is the highest affinity receptor.". J. Biol. Chem. 275 (30): 23319–25. doi:10.1074/jbc.M910438199. PMID 10770955. 

External links[edit]

This article incorporates text from the United States National Library of Medicine, which is in the public domain.