| First Author | Pi M | Year | 2005 |
| Journal | Mol Endocrinol | Volume | 19 |
| Issue | 4 | Pages | 1078-87 |
| PubMed ID | 15637145 | Mgi Jnum | J:97178 |
| Mgi Id | MGI:3574705 | Doi | 10.1210/me.2004-0450 |
| Citation | Pi M, et al. (2005) Beta-arrestin- and G protein receptor kinase-mediated calcium-sensing receptor desensitization. Mol Endocrinol 19(4):1078-87 |
| abstractText | Extracellular calcium rapidly controls PTH secretion through binding to the G protein-coupled calcium-sensing receptor (CASR) expressed in parathyroid glands. Very little is known about the regulatory proteins involved in desensitization of CASR. G protein receptor kinases (GRK) and beta-arrestins are important regulators of agonist-dependent desensitization of G protein-coupled receptors. In the present study, we investigated their role in mediating agonist-dependent desensitization of CASR. In heterologous cell culture models, we found that the transfection of GRK4 inhibits CASR signaling by enhancing receptor phosphorylation and beta-arrestin translocation to the CASR. In contrast, we found that overexpression of GRK2 desensitizes CASR by classical mechanisms as well as through phosphorylation-independent mechanisms involving disruption of Galphaq signaling. In addition, we observed lower circulating PTH levels and an attenuated increase in serum PTH after hypocalcemic stimulation in beta-arrestin2 null mice, suggesting a functional role of beta-arrestin2-dependent desensitization pathways in regulating CASR function in vivo. We conclude that GRKs and beta-arrestins play key roles in regulating CASR responsiveness in parathyroid glands. |
