Back to Search Start Over

Molecular basis of parathyroid hormone receptor signaling and trafficking: a family B GPCR paradigm.

Authors :
Vilardaga JP
Romero G
Friedman PA
Gardella TJ
Source :
Cellular and molecular life sciences : CMLS [Cell Mol Life Sci] 2011 Jan; Vol. 68 (1), pp. 1-13. Date of Electronic Publication: 2010 Aug 12.
Publication Year :
2011

Abstract

The parathyroid hormone (PTH) receptor type 1 (PTHR), a G protein-coupled receptor (GPCR), transmits signals to two hormone systems-PTH, endocrine and homeostatic, and PTH-related peptide (PTHrP), paracrine-to regulate different biological processes. PTHR responds to these hormonal stimuli by activating heterotrimeric G proteins, such as G(S) that stimulates cAMP production. It was thought that the PTHR, as for all other GPCRs, is only active and signals through G proteins on the cell membrane, and internalizes into a cell to be desensitized and eventually degraded or recycled. Recent studies with cultured cell and animal models reveal a new pathway that involves sustained cAMP signaling from intracellular domains. Not only do these studies challenge the paradigm that cAMP production triggered by activated GPCRs originates exclusively at the cell membrane but they also advance a comprehensive model to account for the functional differences between PTH and PTHrP acting through the same receptor.

Details

Language :
English
ISSN :
1420-9071
Volume :
68
Issue :
1
Database :
MEDLINE
Journal :
Cellular and molecular life sciences : CMLS
Publication Type :
Academic Journal
Accession number :
20703892
Full Text :
https://doi.org/10.1007/s00018-010-0465-9