title: Phosphorylation of G Protein-Coupled Receptors: From the Barcode Hypothesis to the Flute Model.
abstract: Seven transmembrane G protein-coupled receptors (GPCRs) are often phosphorylated at the C terminus and on intracellular loops in response to various extracellular stimuli. Phosphorylation of GPCRs by GPCR kinases and certain other kinases can promote the recruitment of arrestin molecules. The arrestins critically regulate GPCR functions not only by mediating receptor desensitization and internalization, but also by redirecting signaling to G protein-independent pathways via interactions with numerous downstream effector molecules. Accumulating evidence over the past decade has given rise to the phospho-barcode hypothesis, which states that ligand-specific phosphorylation patterns of a receptor direct its distinct functional outcomes. Our recent work using unnatural amino acid incorporation and fluorine-19 nuclear magnetic resonance (19F-NMR) spectroscopy led to the flute model, which provides preliminary insight into the receptor phospho-coding mechanism, by which receptor phosphorylation patterns are recognized by an array of phosphate-binding pockets on arrestin and are translated into distinct conformations. These selective conformations are recognized by various effector molecules downstream of arrestin. The phospho-barcoding mechanism enables arrestin to recognize a wide range of phosphorylation patterns of GPCRs, contributing to their diverse functions.
authors.affiliation: Key Laboratory Experimental Teratology of the Ministry of Education and Department of Biochemistry and Molecular Biology (Z.Y., Z.L., C.L., P.X., J.-P.S.), Department of Physiology (F.Y., X.Y.), Shandong University School of Medicine, Jinan, Shandong, People's Republic of China; School of Pharmacy, Binzhou Medical University, Yantai, Shandong, People's Republic of China (D.Z.); School of Medicine, Duke University, Durham, North Carolina (A.L., J.-P.S.).
authors.forename: Zhao
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Key Laboratory Experimental Teratology of the Ministry of Education and Department of Biochemistry and Molecular Biology (Z.Y., Z.L., C.L., P.X., J.-P.S.), Department of Physiology (F.Y., X.Y.), Shandong University School of Medicine, Jinan, Shandong, People's Republic of China; School of Pharmacy, Binzhou Medical University, Yantai, Shandong, People's Republic of China (D.Z.); School of Medicine, Duke University, Durham, North Carolina (A.L., J.-P.S.).
authors.forename: Fan
authors.initials: F
authors.lastname: Yang
authors.affiliation: Key Laboratory Experimental Teratology of the Ministry of Education and Department of Biochemistry and Molecular Biology (Z.Y., Z.L., C.L., P.X., J.-P.S.), Department of Physiology (F.Y., X.Y.), Shandong University School of Medicine, Jinan, Shandong, People's Republic of China; School of Pharmacy, Binzhou Medical University, Yantai, Shandong, People's Republic of China (D.Z.); School of Medicine, Duke University, Durham, North Carolina (A.L., J.-P.S.).
authors.forename: Daolai
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Key Laboratory Experimental Teratology of the Ministry of Education and Department of Biochemistry and Molecular Biology (Z.Y., Z.L., C.L., P.X., J.-P.S.), Department of Physiology (F.Y., X.Y.), Shandong University School of Medicine, Jinan, Shandong, People's Republic of China; School of Pharmacy, Binzhou Medical University, Yantai, Shandong, People's Republic of China (D.Z.); School of Medicine, Duke University, Durham, North Carolina (A.L., J.-P.S.).
authors.forename: Zhixin
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Key Laboratory Experimental Teratology of the Ministry of Education and Department of Biochemistry and Molecular Biology (Z.Y., Z.L., C.L., P.X., J.-P.S.), Department of Physiology (F.Y., X.Y.), Shandong University School of Medicine, Jinan, Shandong, People's Republic of China; School of Pharmacy, Binzhou Medical University, Yantai, Shandong, People's Republic of China (D.Z.); School of Medicine, Duke University, Durham, North Carolina (A.L., J.-P.S.).
authors.forename: Amy
authors.initials: A
authors.lastname: Lin
authors.affiliation: Key Laboratory Experimental Teratology of the Ministry of Education and Department of Biochemistry and Molecular Biology (Z.Y., Z.L., C.L., P.X., J.-P.S.), Department of Physiology (F.Y., X.Y.), Shandong University School of Medicine, Jinan, Shandong, People's Republic of China; School of Pharmacy, Binzhou Medical University, Yantai, Shandong, People's Republic of China (D.Z.); School of Medicine, Duke University, Durham, North Carolina (A.L., J.-P.S.).
authors.forename: Chuan
authors.initials: C
authors.lastname: Liu
authors.affiliation: Key Laboratory Experimental Teratology of the Ministry of Education and Department of Biochemistry and Molecular Biology (Z.Y., Z.L., C.L., P.X., J.-P.S.), Department of Physiology (F.Y., X.Y.), Shandong University School of Medicine, Jinan, Shandong, People's Republic of China; School of Pharmacy, Binzhou Medical University, Yantai, Shandong, People's Republic of China (D.Z.); School of Medicine, Duke University, Durham, North Carolina (A.L., J.-P.S.).
authors.forename: Peng
authors.initials: P
authors.lastname: Xiao
authors.affiliation: Key Laboratory Experimental Teratology of the Ministry of Education and Department of Biochemistry and Molecular Biology (Z.Y., Z.L., C.L., P.X., J.-P.S.), Department of Physiology (F.Y., X.Y.), Shandong University School of Medicine, Jinan, Shandong, People's Republic of China; School of Pharmacy, Binzhou Medical University, Yantai, Shandong, People's Republic of China (D.Z.); School of Medicine, Duke University, Durham, North Carolina (A.L., J.-P.S.).
authors.forename: Xiao
authors.initials: X
authors.lastname: Yu
authors.affiliation: Key Laboratory Experimental Teratology of the Ministry of Education and Department of Biochemistry and Molecular Biology (Z.Y., Z.L., C.L., P.X., J.-P.S.), Department of Physiology (F.Y., X.Y.), Shandong University School of Medicine, Jinan, Shandong, People's Republic of China; School of Pharmacy, Binzhou Medical University, Yantai, Shandong, People's Republic of China (D.Z.); School of Medicine, Duke University, Durham, North Carolina (A.L., J.-P.S.) sunjinpeng@sdu.edu.cn.
authors.forename: Jin-Peng
authors.initials: JP
authors.lastname: Sun
mesh_terms: D000818:Animals; D006801:Humans; D010766:Phosphorylation; D011487:Protein Conformation; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D000071559:beta-Arrestin 1 / Q000502:physiology
chemical_list: D043562:Receptors, G-Protein-Coupled; D000071559:beta-Arrestin 1