Regulation of Cellular Signal Transduction Pathways by the Extracellular Calcium-Sensing Receptor

The extracellular calcium-sensing receptor (CaR) is a class III G-protein coupled receptor that coordinates cellular responses to changes in extracellular free Ca2+ or amino acid concentrations as well as ionic strength and pH. It regulates signalling cascades via recruiting and controlling the activities of various heterotrimeric G-proteins, including Gq/11, Gi/0, and G12/13, even Gs in some "unusual" circumstances, thereby inducing changes in the metabolism of membrane lipids, the phosphorylation state of protein kinases and their targets, the activation state of monomeric G-proteins and the levels of intracellular second messengers including cAMP, Ca2+ ions, fatty acids and other small molecules. According to its site(s) of expression and available signalling pathways, the CaR modulates cell proliferation and survival, differentiation, peptide hormone secretion, ion and water transport and various other processes. In this article we consider the complex intracellular mechanisms by which the CaR elicits its cellular functions. We also consider some of the better understood CaR-regulated cell functions and the nature of the signalling mechanisms that support them.