RT Journal Article
SR Electronic
T1 Phosphorylation of G Protein-Coupled Receptors: From the Barcode Hypothesis to the Flute Model
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 201
OP 210
DO 10.1124/mol.116.107839
VO 92
IS 3
A1 Zhao Yang
A1 Fan Yang
A1 Daolai Zhang
A1 Zhixin Liu
A1 Amy Lin
A1 Chuan Liu
A1 Peng Xiao
A1 Xiao Yu
A1 Jin-Peng Sun
YR 2017
UL http://molpharm.aspetjournals.org/content/92/3/201.abstract
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.