RT Journal Article
SR Electronic
T1 CXCR4/ACKR3 phosphorylation and recruitment of interacting proteins: key mechanisms regulating their functional status
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP mol.118.115360
DO 10.1124/mol.118.115360
A1 Amos Fumagalli
A1 Aurelien Zarca
A1 Maria Neves
A1 Birgit Caspar
A1 Stephen J Hill
A1 Federico Mayor
A1 Martine J Smit
A1 Philippe Marin
YR 2019
UL http://molpharm.aspetjournals.org/content/early/2019/03/05/mol.118.115360.abstract
AB The C-X-C chemokine receptor type 4 (CXCR4) and the atypical chemokine receptor 3 (ACKR3/CXCR7) are class A G protein-coupled receptors (GPCRs). Accumulating evidence indicates that GPCR sub-cellular localization, trafficking, transduction properties and, ultimately, their pathophysiological functions are regulated by both interacting proteins and post-translational modifications. This has encouraged the development of novel techniques to characterize the GPCR interactome and to identify residues subjected to post-translational modifications, with a special focus on phosphorylation. This review first describes state-of-the-art methods for the identification of GPCR-interacting proteins and GPCR phosphorylated sites. In addition, we provide an overview of the current knowledge of CXCR4 and ACKR3 post-translational modifications and an exhaustive list of previously identified CXCR4 or ACKR3 interacting proteins. We then describe studies highlighting the importance of the reciprocal influence of CXCR4/ACKR3 interactomes and phosphorylation state. We also discuss their impact on the functional status of each receptor. These studies suggest that deeper knowledge of the CXCR4/ACKR3 interactomes along with their phosphorylation and ubiquitination status would shed new lights on their regulation and pathophysiological functions.