Determination of GPCR Phosphorylation Status: Establishing a Phosphorylation Barcode

Current Protocols in Pharmacology
Rudi PrihandokoAdrian J Butcher

Abstract

G protein-coupled receptors (GPCRs) are rapidly phosphorylated following agonist occupation in a process that mediates receptor uncoupling from its cognate G protein, a process referred to as desensitization. In addition, this process provides a mechanism by which receptors can engage with arrestin adaptor molecules and couple to downstream signaling pathways. The importance of this regulatory process has been highlighted recently by the understanding that ligands can direct receptor signaling along one pathway in preference to another, the phenomenon of signaling bias that is partly mediated by the phosphorylation status or phosphorylation barcode of the receptor. Methods to determine the phosphorylation status of a GPCR in vitro and in vivo are necessary to understand not only the physiological mechanisms involved in GPCR signaling, but also to fully examine the signaling properties of GPCR ligands. This unit describes detailed methods for determining the overall phosphorylation pattern on a receptor (the phosphorylation barcode), as well as mass spectrometry approaches that can define the precise sites that become phosphorylated. These techniques, coupled with the generation and characterization of receptor phosphorylation-s...Continue Reading

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Citations

Mar 28, 2019·Pharmacological Reviews·Terry Kenakin
Apr 24, 2020·Organic & Biomolecular Chemistry·Mamidi SamarasimhareddyAssaf Friedler
Feb 22, 2017·Frontiers in Endocrinology·Davids FridmanisJanis Klovins
Jun 7, 2018·Nature Structural & Molecular Biology·Christopher J Draper-Joyce, Arthur Christopoulos
Jul 31, 2019·Applied Microbiology and Biotechnology·Jie WangHaiying Hang
Jan 10, 2021·Biochimica Et Biophysica Acta. Proteins and Proteomics·Yaejin YunHyung Ho Lee
Jan 29, 2021·The FEBS Journal·Mark SoaveStephen J Hill

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