期刊
CELLULAR AND MOLECULAR LIFE SCIENCES
卷 68, 期 1, 页码 1-13出版社
SPRINGER BASEL AG
DOI: 10.1007/s00018-010-0465-9
关键词
G protein-coupled receptor; Parathyroid hormone; Cyclic AMP; G proteins; Internalization; Signaling selectivity; Signaling endosomes
资金
- National Institutes of Health [DK087688, DK69998, DK11794]
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [R01DK054171, R01DK069998, R01DK087688, P01DK011794] Funding Source: NIH RePORTER
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.
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