Parathyroid hormone 1 receptor explained

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 protein, which activates 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

Further reading

External links

Notes and References

  1. Mannstadt M, Jüppner H, Gardella TJ . Receptors for PTH and PTHrP: their biological importance and functional properties . The American Journal of Physiology . 277 . 5 Pt 2 . F665-75 . Nov 1999 . 10564229 . 10.1152/ajprenal.1999.277.5.F665. 2007-12-17 . https://web.archive.org/web/20090213101535/http://ajprenal.physiology.org/cgi/content/abstract/277/5/F665 . 2009-02-13 . dead .
  2. Offermanns S, Iida-Klein A, Segre GV, Simon MI . 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 . 10.1210/mend.10.5.8732687 . 8732687 . free .
  3. Web site: Entrez Gene: PTH1R parathyroid hormone 1 receptor .
  4. Yamaguchi T, Hosomichi K, Narita A, Shirota T, Tomoyasu Y, Maki K, Inoue I . 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 . 21404329 . 10.1002/jbmr.385 . 23855913 . free .
  5. Mahon MJ, Donowitz M, Yun CC, Segre GV . Na(+)/H(+) exchanger regulatory factor 2 directs parathyroid hormone 1 receptor signalling . Nature . 417 . 6891 . 858–61 . Jun 2002 . 12075354 . 10.1038/nature00816 . 2002Natur.417..858M . 4379134 .