Role for the C-terminus in agonist-induced μ opioid receptor phosphorylation and desensitization

Hong Bing Deng, Yunkai Yu, Youngshil Pak, Brian F. O'Dowd, Susan R. George, Christopher K. Surratt, George R. Uhl, Jia Bei Wang

Research output: Contribution to journalArticle

Abstract

Determining which domains and amino acid residues of the μ opioid receptor are phosphorylated is critical for understanding the mechanism of μ opioid receptor phosphorylation. The role of the C-terminus of the receptor was investigated by examining the C-terminally truncated or point-mutated μ opioid receptors in receptor phosphorylation and desensitization. Both wild- type and mutated receptors were stably expressed in Chinese hamster ovary (CHO) cells. The receptor expression was confirmed by receptor radioligand binding and immunoblottting. After exposure to 5 μM of DAMGO, phosphorylation of the C-terminally truncated receptor and the mutant receptor T394A was reduced to 40 and 10% of that of the wild-type receptor, respectively. Mutation effects on agonist-induced desensitization were studied using adenylyl cyclase inhibition assays. The C-terminally truncated receptor and mutant receptor T394A both showed complete loss of DAMGO-induced desensitization, while the mutant T/S7A receptor only lost part of its ability to desensitize. Taken together, these results suggest that the C- terminus of the μ opioid receptor participates in receptor phosphorylation and desensitization with threonine 394, a crucial residue for both features. DAMGO-induced μ opioid receptor phosphorylation and desensitization are associated and appear to involve both the μ opioid receptor C-terminus and other domains of the receptor.

Original languageEnglish (US)
Pages (from-to)5492-5499
Number of pages8
JournalBiochemistry®
Volume39
Issue number18
DOIs
Publication statusPublished - May 9 2000

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ASJC Scopus subject areas

  • Biochemistry

Cite this

Deng, H. B., Yu, Y., Pak, Y., O'Dowd, B. F., George, S. R., Surratt, C. K., ... Wang, J. B. (2000). Role for the C-terminus in agonist-induced μ opioid receptor phosphorylation and desensitization. Biochemistry®, 39(18), 5492-5499. https://doi.org/10.1021/bi991938b