Affiliation:
1. Laboratory for GPCR Biology, Department of Pharmacology and Chemical Biology, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania
Abstract
The canonical model for G protein-coupled receptors (GPCRs) activation assumes that stimulation of heterotrimeric G protein signaling upon ligand binding occurs solely at the cell surface and that duration of the stimulation is transient to prevent overstimulation. In this model, GPCR signaling is turned-off by receptor phosphorylation via GPCR kinases (GRKs) and subsequent recruitment of β-arrestins, resulting in receptor internalization into endosomes. Internalized receptors can then recycle back to the cell surface or be trafficked to lysosomes for degradation. However, over the last decade, this model has been extended by discovering that some internalized GPCRs continue to signal via G proteins from endosomes. This is the case for the parathyroid hormone (PTH) type 1 receptor (PTHR), which engages on sustained cAMP signaling from endosomes upon PTH stimulation. Accumulative evidence shows that the location of signaling has an impact on the physiological effects of GPCR signaling. This mini-review discusses recent insights into the mechanisms of PTHR endosomal signaling and its physiological impact.
Funder
HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases
Publisher
American Physiological Society
Cited by
7 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献