TY - JOUR T1 - CXCR4/ACKR3 Phosphorylation and Recruitment of Interacting Proteins: Key Mechanisms Regulating Their Functional Status JF - Molecular Pharmacology JO - Mol Pharmacol SP - 794 LP - 808 DO - 10.1124/mol.118.115360 VL - 96 IS - 6 AU - Amos Fumagalli AU - Aurélien Zarca AU - Maria Neves AU - Birgit Caspar AU - Stephen J. Hill AU - Federico Mayor, Jr. AU - Martine J. Smit AU - Philippe Marin Y1 - 2019/12/01 UR - http://molpharm.aspetjournals.org/content/96/6/794.abstract N2 - The C-X-C motif 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 subcellular 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 states. 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 light on their regulation and pathophysiological functions. ER -