Abstract
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.
Original language | English |
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Pages (from-to) | 794-808 |
Number of pages | 15 |
Journal | Molecular pharmacology |
Volume | 96 |
Issue number | 6 |
DOIs | |
Publication status | Published - 1 Dec 2019 |
Funding
This research was funded by a European Union’s Horizon2020 MSCA Program [Grant agreement 641833 (ONCORNET)]; A.F. and P.M. are also supported by CNRS, INSERM, Université de Montpellier and Fondation pour la Recherche Médicale (FRM); F.M. laboratory is also supported by grants from Ministerio de Economía; Industria y Competitividad (MINECO) of Spain [Grant SAF2017-84125-R]; CIBERCV-Instituto de Salud Carlos III, Spain [Grant CB16/11/00278] to F.M., cofunded with European FEDER contribution); Comunidad de Madrid-B2017/BMD-3671-INFLAMUNE; and Fundación Ramón Areces. 1A.Z. and M.N. contributed equally to this work. https://doi.org/10.1124/mol.118.115360.
Funders | Funder number |
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CIBERCV-Instituto de Salud Carlos III | CB16/11/00278 |
European Union’s Horizon2020 MSCA | |
Industria y Competitividad | |
Ministerio de Economía | |
Fundación Ramón Areces | |
Horizon 2020 Framework Programme | 641833 |
Institut national de la santé et de la recherche médicale | |
Fondation pour la Recherche Médicale | |
Ministerio de Economía y Competitividad | SAF2017-84125-R |
Centre National de la Recherche Scientifique | |
Université de Montpellier | |
European Regional Development Fund | Madrid-B2017/BMD-3671-INFLAMUNE |