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

FEBS Letters

Seuwen, Klaus¹  Schneider, Helmut¹  Feyen, Jean H.M.¹ 

[1] Preclinical Research, Sandoz Pharma AG, CH-4002 Basel, Switzerland

关键词: Parathyroid hormone;    Receptor;    G protein;    Adenylyl cyclase;    Phosphoinositide;    AC;    adenylyl cyclase;    Gs and Gi;    stimulatory and inhibitory G protein of adenylyl cyclase;    respectively;    Gq;    stimulatory G protein of PI-PLC;    IP;    inositol phosphate;    PI;    phosphoinositide;    PI-PLC;    phosphoinositide-specific phospholipase C;    PTH;    parathyroid hormone;    hPTH;    human parathyroid hormone;    cPTHrP;    chicken parathyroid hormone-related protein;    PTX;    pertussis toxin;    HEPES;    4-(2-hydroxyethyl)-piperazineethanesulfonic acid;    IBMX;    isobutylmethylxanthine;    TCA;    trichloroacetic acid;    293 cells;    human embryonic kidney 293 cell line;   

DOI  :  10.1016/0014-5793(94)00878-7

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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 G_i 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 G_s

【 授权许可】

Unknown