The C‐terminal domain of the human EP4 receptor confers agonist‐induced receptor desensitization in a receptor hybrid with the rat EP3β receptor

FEBS Letters

Hänecke, Kristina¹  Neuschäfer-Rube, Frank¹  Püschel, Gerhard P¹ 

[1] Institut für Biochemie und Molekulare Zellbiologie, Humboldtallee 23, 37073 Göttingen, Germany

关键词: Prostaglandin receptor;    Chimeric receptor;    Receptor desensitization;    G protein-coupled receptor kinase;    G protein coupling;    CHO cells;    Chinese hamster ovary cells;    DMEM;    Dulbecco's modified Eagle medium;    EPR;    E-prostaglandin receptor;    FCS;    fetal calf serum;    Gx;    heterotrimeric Gx protein;    GPCR;    G protein-coupled receptor;    GRK;    G protein-coupled receptor kinase;    HAM-F12;    nutrient mixture Ham's F-12;    IBMX;    3-isobutyl-1-methylxanthine;    MBS;    modified bovine serum;    MEM;    minimal essential medium;    MES;    4-morpholine-ethanesulfonic acid;    PCR;    polymerase chain reaction;    PTX;    pertussis toxin;    PG;    prostaglandin;   

DOI  :  10.1016/S0014-5793(97)01105-8

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Prostaglandin E₂ receptors (EPR), which belong to the family of heterotrimeric G protein-coupled ectoreceptors with seven transmembrane domains, can be classified into four subtypes according to their ligand binding and G protein coupling specificity. Of these, EP_3βR is coupled to G_i, whereas EP₄R is coupled to G_s. EP₄R, in contrast to EP_3βR, shows agonist-induced desensitization. The C-terminal domain and the third intracellular loop of these receptors have been implicated in G protein coupling specificity and desensitization. Here, receptor hybrids consisting of the main portion of rat EP_3βR and either the C-terminal domain or the third intracellular loop of human EP₄R were used to study the contribution of the respective receptor domains to G protein coupling and desensitization. Neither the EP₄R C-terminal domain nor the EP₄R third intracellular loop alone was sufficient to change the coupling specificity of the rEP₃hEP₄ receptor hybrids from G_i to G_s or to confer additional G_s coupling. However, the EP₄R C-terminal domain but not the third intracellular loop was necessary and sufficient to mediate rapid agonist-induced, second messenger-independent desensitization in the G_i-coupled hybrid receptors.

【 授权许可】

Unknown