RGD Reference Report - The parathyroid hormone receptorsome and the potential for therapeutic intervention. - Rat Genome Database

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The parathyroid hormone receptorsome and the potential for therapeutic intervention.

Authors: Mahon, MJ 
Citation: Mahon MJ Curr Drug Targets. 2012 Jan;13(1):116-28.
RGD ID: 7207465
Pubmed: PMID:21777186   (View Abstract at PubMed)

The parathyroid hormone 1 receptor (PTH1R) is activated by parathyroid hormone (PTH) and parathyroid hormone related protein (PTHrP), hormones that mediate mineral ion homeostasis and tissue development, respectively. These diverse actions mediated by one receptor are likely due to the formation of cell-specific receptorsome complexes with cytosolic constituents. Through the second and third intracellular loops, the PTH1R couples to several G protein subclasses, including Gs, Gq/11, Gi/o and G12/13, resulting in the activation of many pathways. The PTH1R carboxy-terminal tail directs interactions with a plethora of binding partners. The WD1 and WD7 repeats of the G protein beta subunit directly bind to a novel interaction domain located near the amino-terminal end of the PTH1R carboxy-terminal tail. This Gbetagamma binding site likely contributes to the promiscuous G protein coupling displayed by the PTH1R. Partially overlapping this site is an EF-hand binding domain that directs interactions with calpain, a calcium-activated protease, and calmodulin, a ubiquitous calcium sensor. A lysine-arginine-lysine motif located on the juxtamembrane region of the carboxy-terminal tail mediates interactions with ezrin, an actin-membrane cross-linking protein. The C-terminus of the PTH1R binds to the sodium-hydrogen regulatory factors (NHERFs) via a PDZ domain-mediated interaction, an association that influences signaling and membrane anchoring. Through direct interactions with ezrin and NHERF-1, a PTH1R receptorsome complex exists on apical membranes of the proximal tubule, an assembly that directs PTH-mediated regulation of phosphate transport. Targeting the PTH1R receptorsome will likely enhance therapies directed towards the treatment of osteoporosis and enhancing the hematopoietic stem cell niche.



Molecular Pathway Annotations    Click to see Annotation Detail View

RGD Manual Annotations


  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
PTH1RHumanG protein mediated signaling pathway via Galphaq family  TAS  RGD 
Pth1rRatG protein mediated signaling pathway via Galphaq family  ISOPTH1R (Homo sapiens) RGD 
Pth1rMouseG protein mediated signaling pathway via Galphaq family  ISOPTH1R (Homo sapiens) RGD 
PTH1RHumanG protein mediated signaling pathway via Galphas family  TAS  RGD 
Pth1rRatG protein mediated signaling pathway via Galphas family  ISOPTH1R (Homo sapiens) RGD 
Pth1rMouseG protein mediated signaling pathway via Galphas family  ISOPTH1R (Homo sapiens) RGD 
EZRHumanparathyroid hormone signaling pathway   TAS  RGD 
EzrRatparathyroid hormone signaling pathway   ISOEZR (Homo sapiens) RGD 
EzrMouseparathyroid hormone signaling pathway   ISOEZR (Homo sapiens) RGD 
NHERF1Humanparathyroid hormone signaling pathway   TAS  RGD 
NHERF2Humanparathyroid hormone signaling pathway   TAS  RGD 
Nherf1Ratparathyroid hormone signaling pathway   ISONHERF1 (Homo sapiens) RGD 
Nherf1Mouseparathyroid hormone signaling pathway   ISONHERF1 (Homo sapiens) RGD 
Nherf2Ratparathyroid hormone signaling pathway   ISONHERF2 (Homo sapiens) RGD 
Nherf2Mouseparathyroid hormone signaling pathway   ISONHERF2 (Homo sapiens) RGD 
PTHHumanparathyroid hormone signaling pathway   TAS  RGD 
PTH1RHumanparathyroid hormone signaling pathway   TAS  RGD 
PthRatparathyroid hormone signaling pathway   ISOPTH (Homo sapiens) RGD 
PthMouseparathyroid hormone signaling pathway   ISOPTH (Homo sapiens) RGD 
Pth1rRatparathyroid hormone signaling pathway   ISOPTH1R (Homo sapiens) RGD 
Pth1rMouseparathyroid hormone signaling pathway   ISOPTH1R (Homo sapiens) RGD 
Objects Annotated

Genes (Rattus norvegicus)
Ezr  (ezrin)
Nherf1  (NHERF family PDZ scaffold protein 1)
Nherf2  (NHERF family PDZ scaffold protein 2)
Pth  (parathyroid hormone)
Pth1r  (parathyroid hormone 1 receptor)

Genes (Mus musculus)
Ezr  (ezrin)
Nherf1  (NHERF family PDZ scaffold protein 1)
Nherf2  (NHERF family PDZ scaffold protein 2)
Pth  (parathyroid hormone)
Pth1r  (parathyroid hormone 1 receptor)

Genes (Homo sapiens)
EZR  (ezrin)
NHERF1  (NHERF family PDZ scaffold protein 1)
NHERF2  (NHERF family PDZ scaffold protein 2)
PTH  (parathyroid hormone)
PTH1R  (parathyroid hormone 1 receptor)


Additional Information