Regulation of G Protein-Coupled Receptor Kinases by Phospholipids

K.T.      Homan; A.      Glukhova; J.J.G.      Tesmer

Abstract

G protein coupled-receptor (GPCR) kinases (GRKs) initiate the deactivation of GPCRs by phosphorylating their cytoplasmic loops and C-terminal tails. They are regulated not only by allosteric interactions with activated GPCRs, but also by the membrane environment itself. Herein we describe how the various GRKs are recruited to lipid bilayers and, where evident, how specific anionic phospholipids help regulate their activity. Using crystal structures representing each of the three vertebrate GRK subfamilies, we map the lipid binding sites in order to better understand how these enzymes are oriented at the cell surface. This analysis suggests that GRKs bind lipid and active GPCRs in a coordinated manner.

Keywords: G protein-coupled receptor, kinase, phosphorylation, phospholipid, heterotrimeric G proteins, rhodopsin, β adrenergic receptor, phosphatidylinositol-4, 5-bisphosphate, crystallography, palmitoylation, prenylation

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Current Medicinal Chemistry

Title:Regulation of G Protein-Coupled Receptor Kinases by Phospholipids

Volume: 20 Issue: 1

Author(s): K.T. Homan, A. Glukhova and J.J.G. Tesmer

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Abstract: G protein coupled-receptor (GPCR) kinases (GRKs) initiate the deactivation of GPCRs by phosphorylating their cytoplasmic loops and C-terminal tails. They are regulated not only by allosteric interactions with activated GPCRs, but also by the membrane environment itself. Herein we describe how the various GRKs are recruited to lipid bilayers and, where evident, how specific anionic phospholipids help regulate their activity. Using crystal structures representing each of the three vertebrate GRK subfamilies, we map the lipid binding sites in order to better understand how these enzymes are oriented at the cell surface. This analysis suggests that GRKs bind lipid and active GPCRs in a coordinated manner.

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Homan K.T., Glukhova A. and Tesmer J.J.G., Regulation of G Protein-Coupled Receptor Kinases by Phospholipids, Current Medicinal Chemistry 2013; 20 (1) . https://dx.doi.org/10.2174/0929867311302010005

DOI https://dx.doi.org/10.2174/0929867311302010005	Print ISSN 0929-8673
Publisher Name Bentham Science Publisher	Online ISSN 1875-533X

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