The calcium-sensing receptor (CaSR) is a G-protein coupled receptor (GPCR) that belongs to family (or class) C. Class C GPCRs are typified by large extracellular domains of around 450–600 amino acids. At the extreme N-terminus, just to the C-side of the signal peptide, is a large bilobed, nutrient-binding Venus Flytrap (VFT) domain of around 450–550 residues. The CaSR and other class C VFT domains are structurally related to bacterial nutrient-binding, periplasmic binding proteins,10 which act as sensors for the recruitment and activation of nutrient transporters. The CaSR activates various protein kinases including conventional isoforms of PKC, downstream of PI-PLC and Ca2+i mobilization, as well as mitogen-activated protein (MAP) kinases including ERK1/2, p38, and JNK and two key protein kinase regulators of cell fate, Akt and GSK-3. 
The CaSR also couples to Rho kinase under the control of the monomeric G protein, Rho A35 and in the activation of the transcriptional modulator, Serum Response Factor (SRF). CaSR agonists and positive modulators induce pronounced stimulus-biased signaling with application to the understanding of diverse ligand-dependent physiological functions including L-amino acid-induced gut hormone release and Ca2+o-induced control of calcium homeostasis. These insights may also pave the way to the development


1.Conigrave AD,et al. Best Pract Res Clin Endocrinol Metab. 2013 Jun;27(3):315-31.