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The C‐terminal domain of the human EP 4 receptor confers agonist‐induced receptor desensitization in a receptor hybrid with the rat EP 3β receptor
Author(s) -
Neuschäfer-Rube Frank,
Hänecke Kristina,
Püschel Gerhard P
Publication year - 1997
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(97)01105-8
Subject(s) - heterotrimeric g protein , receptor , homologous desensitization , agonist , g protein coupled receptor , g protein , desensitization (medicine) , 5 ht5a receptor , transmembrane domain , biology , intracellular , biophysics , microbiology and biotechnology , chemistry , biochemistry
Prostaglandin E 2 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 3β R is coupled to G i , whereas EP 4 R is coupled to G s . EP 4 R, in contrast to EP 3β R, 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 3β R and either the C‐terminal domain or the third intracellular loop of human EP 4 R were used to study the contribution of the respective receptor domains to G protein coupling and desensitization. Neither the EP 4 R C‐terminal domain nor the EP 4 R third intracellular loop alone was sufficient to change the coupling specificity of the rEP 3 hEP 4 receptor hybrids from G i to G s or to confer additional G s coupling. However, the EP 4 R 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.