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
Parathyroid hormone-related protein (PTHrP) is a proteinaceous hormone and a member of the parathyroid hormone family secreted by mesenchymal stem cells. It is occasionally secreted by cancer cells (for example, breast cancer, certain types of ...
), 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
Phospholipase C (PLC) is a class of membrane-associated enzymes that cleave phospholipids just before the phosphate group (see figure). It is most commonly taken to be synonymous with the human forms of this enzyme, which play an important role ...
.
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
Second messengers are intracellular signaling molecules released by the cell in response to exposure to extracellular signaling molecules—the first messengers. (Intercellular signals, a non-local form or cell signaling, encompassing both first me ...
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 and primary failure of tooth eruption.
Interactions
Parathyroid hormone 1 receptor has been shown to
interact with
Sodium-hydrogen exchange regulatory cofactor 2 and
Sodium-hydrogen antiporter 3 regulator 1.
[
]
Model organisms
Model organism
A model organism (often shortened to model) is a non-human species that is extensively studied to understand particular biological phenomena, with the expectation that discoveries made in the model organism will provide insight into the workin ...
s 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.
See also
* Parathyroid hormone receptor
There are two known parathyroid hormone receptors in mammals termed PTH1R and PTH2R. These receptors bind parathyroid hormone and are members of the GPCR family of transmembrane proteins.
* parathyroid hormone 1 receptor (PTH1R) is the clas ...
References
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External links
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{{NLM content
G protein-coupled receptors