TY - JOUR T1 - CXCR4/ACKR3 phosphorylation and recruitment of interacting proteins: key mechanisms regulating their functional status JF - Molecular Pharmacology JO - Mol Pharmacol DO - 10.1124/mol.118.115360 SP - mol.118.115360 AU - Amos Fumagalli AU - Aurelien Zarca AU - Maria Neves AU - Birgit Caspar AU - Stephen J Hill AU - Federico Mayor AU - Martine J Smit AU - Philippe Marin Y1 - 2019/01/01 UR - http://molpharm.aspetjournals.org/content/early/2019/03/05/mol.118.115360.abstract N2 - 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. ER -