PT  - JOURNAL ARTICLE
AU  - Fumagalli, Amos
AU  - Zarca, Aurélien
AU  - Neves, Maria
AU  - Caspar, Birgit
AU  - Hill, Stephen J.
AU  - Mayor, Federico
AU  - Smit, Martine J.
AU  - Marin, Philippe
TI  - CXCR4/ACKR3 Phosphorylation and Recruitment of Interacting Proteins: Key Mechanisms Regulating Their Functional Status
AID  - 10.1124/mol.118.115360
DP  - 2019 Dec 01
TA  - Molecular Pharmacology
PG  - 794--808
VI  - 96
IP  - 6
4099  - http://molpharm.aspetjournals.org/content/96/6/794.short
4100  - http://molpharm.aspetjournals.org/content/96/6/794.full
SO  - Mol Pharmacol2019 Dec 01; 96
AB  - 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.