Biology:Parathyroid hormone 1 receptor
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Short description: Protein-coding gene in the species Homo sapiens
 Generic protein structure example |
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
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
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 this, they also activate the phosphatidylinositol-calcium second messenger system.
Pathology
Defects in this receptor are known to be the cause of Jansen's metaphyseal chondrodysplasia (JMC) and chondrodysplasia Blomstrand type (BOCD) as well as enchondromatosis[3] and primary failure of tooth eruption.[4]
Interactions
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
References
- ↑ "Receptors for PTH and PTHrP: their biological importance and functional properties". The American Journal of Physiology 277 (5 Pt 2): F665-75. Nov 1999. doi:10.1152/ajprenal.1999.277.5.F665. PMID 10564229. http://ajprenal.physiology.org/cgi/content/abstract/277/5/F665. Retrieved 2007-12-17.
- ↑ "G alpha q family members couple parathyroid hormone (PTH)/PTH-related peptide and calcitonin receptors to phospholipase C in COS-7 cells". Molecular Endocrinology 10 (5): 566–74. May 1996. doi:10.1210/mend.10.5.8732687. PMID 8732687.
- ↑ "Entrez Gene: PTH1R parathyroid hormone 1 receptor". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=5745.
- ↑ "Exome resequencing combined with linkage analysis identifies novel PTH1R variants in primary failure of tooth eruption in Japanese". Journal of Bone and Mineral Research 26 (7): 1655–61. Jul 2011. doi:10.1002/jbmr.385. PMID 21404329.
- ↑ 5.0 5.1 "Na(+)/H(+ ) exchanger regulatory factor 2 directs parathyroid hormone 1 receptor signalling". Nature 417 (6891): 858–61. Jun 2002. doi:10.1038/nature00816. PMID 12075354. Bibcode: 2002Natur.417..858M.
Further reading
- "Dimeric arrangement of the parathyroid hormone receptor and a structural mechanism for ligand-induced dissociation". The Journal of Biological Chemistry 285 (16): 12435–44. Apr 2010. doi:10.1074/jbc.M109.093138. PMID 20172855.
- "[Hereditary skeletal dysplasias and FGFR3 and PTHR1 signaling pathways"]. Médecine/Sciences 21 (11): 954–61. Nov 2005. doi:10.1051/medsci/20052111954. PMID 16274647. http://www.erudit.org/fr/revues/ms/2005-v21-n11-ms1020/011961ar.pdf.
- "Treatment of Haemophilus aphrophilus endocarditis with ciprofloxacin". The Journal of Infection 24 (3): 317–20. May 1992. doi:10.1016/S0163-4453(05)80037-4. PMID 1602151.
- "A constitutively active mutant PTH-PTHrP receptor in Jansen-type metaphyseal chondrodysplasia". Science 268 (5207): 98–100. Apr 1995. doi:10.1126/science.7701349. PMID 7701349. Bibcode: 1995Sci...268...98S.
- "Pseudohypoparathyroidism type Ib is not caused by mutations in the coding exons of the human parathyroid hormone (PTH)/PTH-related peptide receptor gene". The Journal of Clinical Endocrinology and Metabolism 80 (5): 1611–21. May 1995. doi:10.1210/jcem.80.5.7745008. PMID 7745008.
- "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. Mar 1994. doi:10.1006/geno.1994.1122. PMID 8020952.
- "Molecular cloning of the gene encoding the mouse parathyroid hormone/parathyroid hormone-related peptide receptor". Proceedings of the National Academy of Sciences of the United States of America 91 (11): 5051–5. May 1994. doi:10.1073/pnas.91.11.5051. PMID 8197183. Bibcode: 1994PNAS...91.5051M.
- "Identical complementary deoxyribonucleic acids encode a human renal and bone parathyroid hormone (PTH)/PTH-related peptide receptor". Endocrinology 132 (5): 2157–65. May 1993. doi:10.1210/endo.132.5.8386612. PMID 8386612.
- "Cloning and functional expression of a human parathyroid hormone receptor". European Journal of Pharmacology 246 (2): 149–55. Jul 1993. doi:10.1016/0922-4106(93)90092-N. PMID 8397094.
- "Constitutively activated receptors for parathyroid hormone and parathyroid hormone-related peptide in Jansen's metaphyseal chondrodysplasia". The New England Journal of Medicine 335 (10): 708–14. Sep 1996. doi:10.1056/NEJM199609053351004. PMID 8703170.
- "Direct mapping of an agonist-binding domain within the parathyroid hormone/parathyroid hormone-related protein receptor by photoaffinity crosslinking". Proceedings of the National Academy of Sciences of the United States of America 94 (8): 3644–9. Apr 1997. doi:10.1073/pnas.94.8.3644. PMID 9108031. Bibcode: 1997PNAS...94.3644Z.
- "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". Molecular Endocrinology 11 (7): 851–8. Jun 1997. doi:10.1210/mend.11.7.9934. PMID 9178745.
- "Absence of functional receptors for parathyroid hormone and parathyroid hormone-related peptide in Blomstrand chondrodysplasia". The Journal of Clinical Investigation 102 (1): 34–40. Jul 1998. doi:10.1172/JCI2918. PMID 9649554.
- "Binding domain of human parathyroid hormone receptor: from conformation to function". Biochemistry 37 (37): 12737–43. Sep 1998. doi:10.1021/bi981265h. PMID 9737850.
- "A homozygous inactivating mutation in the parathyroid hormone/parathyroid hormone-related peptide receptor causing Blomstrand chondrodysplasia". The Journal of Clinical Endocrinology and Metabolism 83 (9): 3365–8. Sep 1998. doi:10.1210/jcem.83.9.5243. PMID 9745456.
- "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". Molecular Endocrinology 12 (11): 1673–83. Nov 1998. doi:10.1210/mend.12.11.0198. PMID 9817594.
- "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. Feb 1999. doi:10.1210/endo.140.2.6573. PMID 9927325.
- "A novel parathyroid hormone (PTH)/PTH-related peptide receptor mutation in Jansen's metaphyseal chondrodysplasia". The Journal of Clinical Endocrinology and Metabolism 84 (9): 3052–7. Sep 1999. doi:10.1210/jcem.84.9.6000. PMID 10487664.
- "A frame-shift mutation in the type I parathyroid hormone (PTH)/PTH-related peptide receptor causing Blomstrand lethal osteochondrodysplasia". The Journal of Clinical Endocrinology and Metabolism 84 (10): 3713–20. Oct 1999. doi:10.1210/jcem.84.10.6033. PMID 10523019.
- "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. Mar 2000. doi:10.1016/S8756-3282(99)00264-1. PMID 10709993.
- "Temperature-sensitive differential affinity of TRAIL for its receptors. DR5 is the highest affinity receptor". The Journal of Biological Chemistry 275 (30): 23319–25. Jul 2000. doi:10.1074/jbc.M910438199. PMID 10770955.
External links
- "Parathyroid Hormone Receptors: PTH1". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. http://www.iuphar-db.org/GPCR/ChapterMenuForward?chapterID=1334.
- Receptor,+Parathyroid+Hormone,+Type+1 at the US National Library of Medicine Medical Subject Headings (MeSH)
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
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