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Molecular basis of parathyroid hormone receptor signaling and trafficking: a family B GPCR paradigm.
- 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.
- Subjects :
- Animals
Cell Membrane metabolism
Cyclic AMP metabolism
GTP-Binding Proteins metabolism
Humans
Models, Biological
Parathyroid Hormone chemistry
Parathyroid Hormone metabolism
Parathyroid Hormone-Related Protein metabolism
Protein Structure, Tertiary
Receptor, Parathyroid Hormone, Type 1 chemistry
Receptor, Parathyroid Hormone, Type 1 metabolism
Structure-Activity Relationship
Receptor, Parathyroid Hormone, Type 1 physiology
Signal Transduction
Subjects
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