Two C-terminal amino acids, Ser334 and Ser335, are required for homologous desensitization and agonist-induced phosphorylation of opioid receptor-like 1 receptors

Hung Li Wang, Yo Li Kuo, Chia Yu Hsu, Pei Chen Huang, Allen H. Li, An Hsun Chou, Tu Hsueh Yeh, Ying Ling Chen

研究成果: 雜誌貢獻文章

5 引文 斯高帕斯(Scopus)

摘要

Various cellular signaling pathways induced by nociceptin activation of ORL1 (opioid receptor-like 1 receptor) develop homologous desensitization. Multiple lines of evidence suggest that agonist-induced phosphorylation of serine (Ser)/threonine (Thr) residues at intracellular carboxyl tail leads to homologous desensitization of G protein-coupled receptors. In the present study, we investigated the functional role played by C-terminal Ser/Thr residues in agonist-induced desensitization and phosphorylation of ORL1. In HEK 293 cells expressing wild-type ORL1 and ORL1(CΔ21), which lacks C-terminal 21 amino acids, nociceptin inhibition of adenylate cyclase activity exhibited homologous desensitization after 1 h pretreatment of nociceptin. In contrast, ORL1(CΔ34), which differs with ORL1(CΔ21) by lacking C-terminal Ser334, Ser335 and Ser343 residues, failed to develop agonist-induced desensitization. Point mutant (S343A) ORL1 underwent homologous desensitization after nociceptin pretreatment. Substituting Ser 334 or Ser335 with alanine greatly impaired nociceptin-induced ORL1 desensitization. In HEK 293 cells expressing double mutant (S334A/S335A) ORL1, nociceptin pretreatment failed to significantly affect the efficacy and potency by which nociceptin inhibits forskolin-stimulated cAMP formation. Mutation of Ser334 and Ser 335 also greatly reduced nociceptin-induced ORL1 phosphorylation. These results suggest that two C-terminal serine residues, Ser334 and Ser335, are required for homologous desensitization and agonist-induced phosphorylation of ORL1.
原文英語
頁(從 - 到)670-678
頁數9
期刊Cellular Signalling
18
發行號5
DOIs
出版狀態已發佈 - 五月 1 2006

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ASJC Scopus subject areas

  • Cell Biology

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