A C-terminally truncated human parathyroid hormone receptor is functional and activates multiple G proteins.

We have investigated the role of the C-terminal cytoplasmic domain of the human PTH receptor in effector coupling. Following transient expression in COS-1 cells, coupling to both AC and PI-PLC was observed with the full-length receptor. Progressive C-terminal truncations did not dissociate activation of the two signalling systems. In stably transfected 293 cells, however, the full-length receptor as well as the majority of truncated constructs stimulated AC exclusively but failed to activate PI-PLC. Activation of both signalling systems was again observed following stable expression of a severely truncated receptor (R483) in 293 cells. In this case, pertussis toxin was also found to potentiate the cAMP response to hPTH-(1-38) significantly, indicating functional coupling of R483 to Gi proteins. Our results suggest that a core region of the human PTH receptor (first, second, third intracellular loop) can interact promiscuously with different G proteins and that the C-terminus of the full-length receptor directs the receptor towards an interaction with Gs.