title: Posttranslation modification of G protein-coupled receptor in relationship to biased agonism.
abstract: Biased signaling has been reported with a series of G protein-coupled receptors (GPCRs), including β(2)-adrenergic receptor and μ-opioid receptor (OPRM1). The concept of biased signaling suggests that the agonists of one particular receptor may activate the downstream signaling pathways with different efficacies. Thus in an extreme case, agonists might activate different sets of signaling pathways, which provide a new route to develop drugs with increased efficacies and decreased side effects. Among the many factors, posttranslation modifications of receptor proteins have major roles in influencing the biased signaling. Take OPRM1, for example, the phosphorylation and palmitoylation of receptor can regulate the biased signaling induced by agonists. Thus, by modulating these posttranslation modifications, the biased signaling of GPCRs can be regulated. In addition, although it is not considered as posttranslation modification normally, the distribution of GPCRs on cell membrane, especially the distribution between lipid-raft and non-raft microdomains, also contributes to the biased signaling. Thus in this chapter, we described the methods used in our laboratory to study receptor phosphorylation, receptor palmitoylation, and membrane distribution of receptor by using OPRM1 as a model. A functional model was also provided on these posttranslational modifications at the last section of this chapter.
authors: Stem Cell and Cancer Biology Group, Key Laboratory of Regenerative Biology, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China. zhenhui2055@hotmail.com
authors: Hui
authors: H
authors: Zheng
authors: Horace H
authors: HH
authors: Loh
authors: Ping-Yee
authors: PY
authors: Law
mesh_terms: D000818:Animals; D019390:Arrestins / Q000235:genetics / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D005048:Etorphine / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D057809:HEK293 Cells; D006801:Humans; D054878:Lipoylation / Q000187:drug effects; D021962:Membrane Microdomains / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D009020:Morphine / Q000494:pharmacology; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D061251:Primary Cell Culture; D011499:Protein Processing, Post-Translational / Q000187:drug effects*; D051381:Rats; D017450:Receptors, Opioid, mu / Q000819:agonists* / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D000071557:beta-Arrestins
chemical_list: D019390:Arrestins; C485764:OPRM1 protein, human; D017450:Receptors, Opioid, mu; D000071557:beta-Arrestins; D005048:Etorphine; D009020:Morphine; D000242:Cyclic AMP
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