Parathyroid hormone 1 receptor: Difference between revisions

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{{Infobox_gene}}
{{Infobox_gene}}
'''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 [[parathyroid hormone receptor|receptor]] for parathyroid hormone ([[parathyroid hormone|PTH]]) and for parathyroid hormone-related protein ([[Parathyroid hormone-related protein|PTHrP]]), also called parathyroid hormone-like hormone (PTHLH).
'''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 [[parathyroid hormone receptor|receptor]] for parathyroid hormone ([[parathyroid hormone|PTH]]) and for parathyroid hormone-related protein ([[Parathyroid hormone-related protein|PTHrP]]), also called parathyroid hormone-like hormone (PTHLH).


== Function ==
== 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]].<ref name="pmid10564229">{{cite journal | vauthors = Mannstadt M, Jüppner H, Gardella TJ | title = Receptors for PTH and PTHrP: their biological importance and functional properties | journal = The American Journal of Physiology | volume = 277 | issue = 5 Pt 2 | pages = F665-75 | date = Nov 1999 | pmid = 10564229 | doi =  | url = http://ajprenal.physiology.org/cgi/content/abstract/277/5/F665 }}</ref><ref name="pmid8732687">{{cite journal | vauthors = Offermanns S, Iida-Klein A, Segre GV, Simon MI | title = G alpha q family members couple parathyroid hormone (PTH)/PTH-related peptide and calcitonin receptors to phospholipase C in COS-7 cells | journal = Molecular Endocrinology | volume = 10 | issue = 5 | pages = 566–74 | date = May 1996 | pmid = 8732687 | doi = 10.1210/me.10.5.566 }}</ref>
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]].<ref name="pmid10564229">{{cite journal | vauthors = Mannstadt M, Jüppner H, Gardella TJ | title = Receptors for PTH and PTHrP: their biological importance and functional properties | journal = The American Journal of Physiology | volume = 277 | issue = 5 Pt 2 | pages = F665-75 | date = Nov 1999 | pmid = 10564229 | doi =  | url = http://ajprenal.physiology.org/cgi/content/abstract/277/5/F665 }}</ref><ref name="pmid8732687">{{cite journal | vauthors = Offermanns S, Iida-Klein A, Segre GV, Simon MI | title = G alpha q family members couple parathyroid hormone (PTH)/PTH-related peptide and calcitonin receptors to phospholipase C in COS-7 cells | journal = Molecular Endocrinology | volume = 10 | issue = 5 | pages = 566–74 | date = May 1996 | pmid = 8732687 | doi = 10.1210/me.10.5.566 }}</ref> 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.
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==
==Mechanism==
It is a member of the [[secretin receptor family|secretin family]] of [[G protein-coupled receptor]]s. The activity of this receptor is mediated by [[Gs protein|G<sub>s</sub>]] [[G proteins]] which activate [[adenylyl cyclase]]. Besides, they also activate [[phosphatidylinositol]]-[[calcium]] [[second messenger]] system.
It is a member of the [[secretin receptor family|secretin family]] of [[G protein-coupled receptor]]s. The activity of this receptor is mediated by [[Gs protein|G<sub>s</sub>]] [[G proteins]], which activate [[adenylyl cyclase]]. Besides this, they also activate the [[phosphatidylinositol]]-[[calcium]] [[second messenger]] system.


==Pathology==
==Pathology==
Defects in this receptor are known to be the cause of [[Jansen's metaphyseal chondrodysplasia]] (JMC), [[chondrodysplasia Blomstrand]] type (BOCD), as well as [[enchondromatosis]] <ref name="entrez">{{cite web | title = Entrez Gene: PTH1R parathyroid hormone 1 receptor | url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=5745| accessdate = }}</ref> and primary failure of tooth eruption.
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]]<ref name="entrez">{{cite web | title = Entrez Gene: PTH1R parathyroid hormone 1 receptor | url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=5745| accessdate = }}</ref> and primary failure of tooth eruption.<ref name=pmid21404329>{{cite journal | vauthors = Yamaguchi T, Hosomichi K, Narita A, Shirota T, Tomoyasu Y, Maki K, Inoue I | title = Exome resequencing combined with linkage analysis identifies novel PTH1R variants in primary failure of tooth eruption in Japanese | journal = Journal of Bone and Mineral Research | volume = 26 | issue = 7 | pages = 1655–61 | date = Jul 2011 | pmid = 21404329 | doi = 10.1002/jbmr.385 }}</ref>
<ref name=pmid21404329>{{cite journal | vauthors = Yamaguchi T, Hosomichi K, Narita A, Shirota T, Tomoyasu Y, Maki K, Inoue I | title = Exome resequencing combined with linkage analysis identifies novel PTH1R variants in primary failure of tooth eruption in Japanese | journal = Journal of Bone and Mineral Research | volume = 26 | issue = 7 | pages = 1655–61 | date = Jul 2011 | pmid = 21404329 | doi = 10.1002/jbmr.385 }}</ref>


== Interactions ==
== Interactions ==
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{{refbegin | 2}}
{{refbegin | 2}}
* {{cite journal | vauthors = Pioszak AA, Harikumar KG, Parker NR, Miller LJ, Xu HE | title = Dimeric arrangement of the parathyroid hormone receptor and a structural mechanism for ligand-induced dissociation | journal = The Journal of Biological Chemistry | volume = 285 | issue = 16 | pages = 12435–44 | date = Apr 2010 | pmid = 20172855 | doi = 10.1074/jbc.M109.093138 | pmc=2852981}}
* {{cite journal | vauthors = Pioszak AA, Harikumar KG, Parker NR, Miller LJ, Xu HE | title = Dimeric arrangement of the parathyroid hormone receptor and a structural mechanism for ligand-induced dissociation | journal = The Journal of Biological Chemistry | volume = 285 | issue = 16 | pages = 12435–44 | date = Apr 2010 | pmid = 20172855 | doi = 10.1074/jbc.M109.093138 | pmc=2852981}}
* {{cite journal | vauthors = Bonaventure J, Silve C | title = [Hereditary skeletal dysplasias and FGFR3 and PTHR1 signaling pathways] | journal = Médecine Sciences | volume = 21 | issue = 11 | pages = 954–61 | date = Nov 2005 | pmid = 16274647 | doi = 10.1051/medsci/20052111954 }}
* {{cite journal | vauthors = Bonaventure J, Silve C | title = [Hereditary skeletal dysplasias and FGFR3 and PTHR1 signaling pathways] | journal = Médecine Sciences | volume = 21 | issue = 11 | pages = 954–61 | date = Nov 2005 | pmid = 16274647 | doi = 10.1051/medsci/20052111954 | url = http://www.erudit.org/fr/revues/ms/2005-v21-n11-ms1020/011961ar.pdf }}
* {{cite journal | vauthors = Dawson SJ, White LA | title = Treatment of Haemophilus aphrophilus endocarditis with ciprofloxacin | journal = The Journal of Infection | volume = 24 | issue = 3 | pages = 317–20 | date = May 1992 | pmid = 1602151 | doi = 10.1016/S0163-4453(05)80037-4 }}
* {{cite journal | vauthors = Dawson SJ, White LA | title = Treatment of Haemophilus aphrophilus endocarditis with ciprofloxacin | journal = The Journal of Infection | volume = 24 | issue = 3 | pages = 317–20 | date = May 1992 | pmid = 1602151 | doi = 10.1016/S0163-4453(05)80037-4 }}
* {{cite journal | vauthors = Schipani E, Kruse K, Jüppner H | title = A constitutively active mutant PTH-PTHrP receptor in Jansen-type metaphyseal chondrodysplasia | journal = Science | volume = 268 | issue = 5207 | pages = 98–100 | date = Apr 1995 | pmid = 7701349 | doi = 10.1126/science.7701349 }}
* {{cite journal | vauthors = Schipani E, Kruse K, Jüppner H | title = A constitutively active mutant PTH-PTHrP receptor in Jansen-type metaphyseal chondrodysplasia | journal = Science | volume = 268 | issue = 5207 | pages = 98–100 | date = Apr 1995 | pmid = 7701349 | doi = 10.1126/science.7701349 }}
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{{NLM content}}
{{NLM content}}


[[Category:G protein coupled receptors]]
[[Category:G protein-coupled receptors]]

Latest revision as of 14:26, 4 November 2018

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SpeciesHumanMouse
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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]

Model organisms

Model organisms have been used in the study of PTH1R function. A conditional knockout mouse line called Pth1rtm1a(EUCOMM)Hmgu was generated at the Wellcome Trust Sanger Institute.[6] Male and female animals underwent a standardized phenotypic screen[7] to determine the effects of deletion.[8][9][10][11] Additional screens performed: - In-depth immunological phenotyping[12]


See also

References

  1. ↑ Mannstadt M, Jüppner H, Gardella TJ (Nov 1999). "Receptors for PTH and PTHrP: their biological importance and functional properties". The American Journal of Physiology. 277 (5 Pt 2): F665–75. PMID 10564229.
  2. ↑ Offermanns S, Iida-Klein A, Segre GV, Simon MI (May 1996). "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. 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 (Jul 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. 26 (7): 1655–61. doi:10.1002/jbmr.385. PMID 21404329.
  5. ↑ 5.0 5.1 Mahon MJ, Donowitz M, Yun CC, Segre GV (Jun 2002). "Na(+)/H(+ ) exchanger regulatory factor 2 directs parathyroid hormone 1 receptor signalling". Nature. 417 (6891): 858–61. doi:10.1038/nature00816. PMID 12075354.
  6. ↑ Gerdin AK (2010). "The Sanger Mouse Genetics Programme: high throughput characterisation of knockout mice". Acta Ophthalmologica. 88: 925–7. doi:10.1111/j.1755-3768.2010.4142.x.
  7. ↑ 7.0 7.1 "International Mouse Phenotyping Consortium".
  8. ↑ Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF, Bradley A (Jun 2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature. 474 (7351): 337–42. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.
  9. ↑ Dolgin E (Jun 2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
  10. ↑ Collins FS, Rossant J, Wurst W (Jan 2007). "A mouse for all reasons". Cell. 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247.
  11. ↑ White JK, Gerdin AK, Karp NA, Ryder E, Buljan M, Bussell JN, Salisbury J, Clare S, Ingham NJ, Podrini C, Houghton R, Estabel J, Bottomley JR, Melvin DG, Sunter D, Adams NC, Tannahill D, Logan DW, Macarthur DG, Flint J, Mahajan VB, Tsang SH, Smyth I, Watt FM, Skarnes WC, Dougan G, Adams DJ, Ramirez-Solis R, Bradley A, Steel KP (Jul 2013). "Genome-wide generation and systematic phenotyping of knockout mice reveals new roles for many genes". Cell. 154 (2): 452–64. doi:10.1016/j.cell.2013.06.022. PMC 3717207. PMID 23870131.
  12. ↑ 12.0 12.1 "Infection and Immunity Immunophenotyping (3i) Consortium".

Further reading

External links

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

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