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.
Schneider
H
H
Sandoz Pharma AG, Basel, Switzerland.
Feyen
J H
JH
Seuwen
K
K
D000262:Adenylyl Cyclases / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006801:Humans; D010281:Parathyroid Hormone / Q000378:metabolism*; D010716:Phosphatidylinositols / Q000378:metabolism; D018016:Receptors, Parathyroid Hormone / Q000235:genetics / Q000378:metabolism*; D017384:Sequence Deletion; D015398:Signal Transduction; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D010738:Type C Phospholipases / Q000378:metabolism
D010281:Parathyroid Hormone; D010716:Phosphatidylinositols; D018016:Receptors, Parathyroid Hormone; D010738:Type C Phospholipases; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases