Phorbol‐ester‐induced phosphorylation of the β2‐adrenergic receptor decreases its coupling to Gs

FEBS Letters

Guilbault, Nathalie¹  Bouvier, Michel¹  Bonin, Hélène¹ 

[1] Department of Biochemistry and Le Groupe de Recherche sur le Système Nerveux Autonome, University of Montreal, Montreal, Canada H3C 4J7

关键词: β2-Adrenergic receptor;    Phosphorylation;    Protein kinase C;    Adenylyl cyclase;    Desensitization;    Phorbol-ester;    Receptor uncoupling;    AR;    adrenergic receptor;    PMA;    4β-phorbol 12β-myristate 13α-acetate;    PKC;    protein kinase C;    Gs;    stimulatory guanine-nucleotide-binding protein;    G1;    inhibitory guanine-nucleotide tide-binding protein;    P1;    phospho-inositides;    [125I]CYP;    [125I]cyonopindolol;    CHW;    Chinese hamster fibroblats;    DMEM;    Dulbecco's minimum Eagle's medium;   

DOI  :  10.1016/0014-5793(91)80159-Z

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Phorbol-esters have been shown to modulated the β-adrenergie-stimulated adenylyl cyclase in a number of cell lines. Here, using site directed mutagenesis, we investigate the role of the β-adrenergic receptor phosphorylation by protein kinase C in this regulatory process. Mutation of the serine-261, -262, -344 and -345 of the β₂-adrenergic receptor prevented the phorbol-ester-induced phosphorylation of the receptor. This mutation also abolished the phorbol-ester-induced decrease in high-affinity agonist binding and potency of the β₂adrenergic receptor. We suggest that protein kinase C mediated phosphorylation of the receptor promotes its functional uncoupling.

【 授权许可】

Unknown