PT  - JOURNAL ARTICLE
AU  - Zhao Yang
AU  - Fan Yang
AU  - Daolai Zhang
AU  - Zhixin Liu
AU  - Amy Lin
AU  - Chuan Liu
AU  - Peng Xiao
AU  - Xiao Yu
AU  - Jin-Peng Sun
TI  - Phosphorylation of G Protein-Coupled Receptors: From the Barcode Hypothesis to the Flute Model
AID  - 10.1124/mol.116.107839
DP  - 2017 Sep 01
TA  - Molecular Pharmacology
PG  - 201--210
VI  - 92
IP  - 3
4099  - http://molpharm.aspetjournals.org/content/92/3/201.short
4100  - http://molpharm.aspetjournals.org/content/92/3/201.full
SO  - Mol Pharmacol2017 Sep 01; 92
AB  - 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.