The role of 14-3-3 proteins in calcium-sensing receptor cell signalling and expression

[Truncated abstract] The calcium-sensing receptor (CaR), belonging to class C of G protein-coupled receptors (GPCRs), is highly expressed in tissues that govern the CaR’s primary role in regulating calcium homeostasis. However, the CaR is expressed in many tissues outside those regulating calcium homeostasis thus reflecting the many different roles that this receptor is now known to play in cell biology, including cell proliferation and the regulation of actin cytoskeleton arrangement, which are regulated through a number of different cell signalling pathways. In recent years, it has become clear that accessory proteins that bind to the CaR, particularly its intracellular tail, can influence the expression of the CaR and/or the activation of its cell signalling pathways. Several accessory proteins that bind to the CaR tail have already been documented and it is hypothesised that there are likely to be more that could influence CaR biology. To this end, our laboratory performed a yeast two-hybrid (Y2H) screen of a haematopoietic cell line cDNA library using the CaR tail as bait. This library was chosen as the CaR is known to be expressed in haematopoietic cells and offered the chance to detect novel interactions with the CaR not detectable in previously screened parathyroid and kidney libraries. Over 100 potential interacting clones were recovered from this screen of which 41 were examined further in this thesis.