Context-Dependent Signaling of CXC Chemokine Receptor 4 and Atypical Chemokine Receptor 3 - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Molecular Pharmacology Année : 2019

Context-Dependent Signaling of CXC Chemokine Receptor 4 and Atypical Chemokine Receptor 3

Joyce Heuninck
  • Fonction : Auteur
Cristina Perpiñá Viciano
  • Fonction : Auteur
Ali Işbilir
  • Fonction : Auteur
Birgit Caspar
  • Fonction : Auteur
Davide Capoferri
  • Fonction : Auteur
Stephen Briddon
  • Fonction : Auteur
Thierry Durroux
Stephen Hill
  • Fonction : Auteur
Jean-Philippe Pin
Carsten Hoffmann
  • Fonction : Auteur

Résumé

G protein-coupled receptors (GPCRs) are regulated by complex molecular mechanisms, both in physiologic and pathologic conditions, and their signaling can be intricate. Many factors influence their signaling behavior, including the type of ligand that activates the GPCR, the presence of interacting partners, the kinetics involved, or their location. The two CXC-type chemokine receptors, CXC chemokine receptor 4 (CXCR4) and atypical chemokine receptor 3 (ACKR3), both members of the GPCR superfamily, are important and established therapeutic targets in relation to cancer, human immunodeficiency virus infection, and inflammatory diseases. Therefore, it is crucial to understand how the signaling of these receptors works to be able to specifically target them. In this review, we discuss how the signaling pathways activated by CXCR4 and ACKR3 can vary in different situations. G protein signaling of CXCR4 depends on the cellular context, and discrepancies exist depending on the cell lines used. ACKR3, as an atypical chemokine receptor, is generally reported to not activate G proteins but can broaden its signaling spectrum upon heteromerization with other receptors, such as CXCR4, endothelial growth factor receptor, or the a 1-adrenergic receptor (a 1-AR). Also, CXCR4 forms heteromers with CC chemokine receptor (CCR) 2, CCR5, the Na 1 / H 1 exchanger regulatory factor 1, CXCR3, a 1-AR, and the opioid receptors, which results in differential signaling from that of the monomeric subunits. In addition, CXCR4 is present on membrane rafts but can go into the nucleus during cancer progression, probably acquiring different signaling properties. In this review, we also provide an overview of the currently known critical amino acids involved in CXCR4 and ACKR3 signaling.
Fichier principal
Vignette du fichier
778.full.pdf (1.16 Mo) Télécharger le fichier
Origine : Fichiers éditeurs autorisés sur une archive ouverte

Dates et versions

hal-02389610 , version 1 (23-11-2020)

Identifiants

Citer

Joyce Heuninck, Cristina Perpiñá Viciano, Ali Işbilir, Birgit Caspar, Davide Capoferri, et al.. Context-Dependent Signaling of CXC Chemokine Receptor 4 and Atypical Chemokine Receptor 3. Molecular Pharmacology, 2019, 96 (6), pp.778-793. ⟨10.1124/mol.118.115477⟩. ⟨hal-02389610⟩
99 Consultations
71 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More