Herman D. Lim
Systematic assessment of chemokine signaling at chemokine receptors ccr4, ccr7 and ccr10
Lim, Herman D.; Robert Lane, J.; Canals, Meritxell; Stone, Martin J.
Authors
ROB LANE ROB.LANE@NOTTINGHAM.AC.UK
Associate Professor
MERITXELL CANALS M.CANALS@NOTTINGHAM.AC.UK
Professor of Cellular Pharmacology
Martin J. Stone
Abstract
Chemokines interact with chemokine receptors in a promiscuous network, such that each receptor can be activated by multiple chemokines. Moreover, different chemokines have been reported to preferentially activate different signalling pathways via the same receptor, a phenomenon known as biased agonism. The human CC chemokine receptors (CCRs) CCR4, CCR7 and CCR10 play important roles in T cell trafficking and have been reported to display biased agonism. To systematically characterize these effects, we analysed G protein-and β-arrestin-mediated signal transduction resulting from stimulation of these receptors by each of their cognate chemokine ligands within the same cellular background. Although the chemokines did not elicit ligand-biased agonism, the three receptors exhibited different arrays of signaling outcomes. Stimulation of CCR4 by either CC chemokine ligand 17 (CCL17) or CCL22 induced β-arrestin recruitment but not G protein-mediated signaling, suggesting that CCR4 has the potential to act as a scavenger receptor. At CCR7, both CCL19 and CCL21 stimulated G protein signaling and β-arrestin recruitment, with CCL19 consistently displaying higher potency. At CCR10, CCL27 and CCL28(4-108) stimulated both G protein signaling and β-arrestin recruitment, whereas CCL28(1-108) was inactive, suggesting that CCL28(4-108) is the biologically relevant form of this chemokine. These comparisons emphasize the intrinsic abilities of different receptors to couple with different downstream signaling pathways. Comparison of these results with previous studies indicates that differential agonism at these receptors may be highly dependent on the cellular context.
Citation
Lim, H. D., Robert Lane, J., Canals, M., & Stone, M. J. (2021). Systematic assessment of chemokine signaling at chemokine receptors ccr4, ccr7 and ccr10. International Journal of Molecular Sciences, 22(8), Article 4232. https://doi.org/10.3390/ijms22084232
Journal Article Type | Article |
---|---|
Acceptance Date | Apr 15, 2021 |
Online Publication Date | Apr 19, 2021 |
Publication Date | Apr 19, 2021 |
Deposit Date | Nov 19, 2021 |
Publicly Available Date | Nov 19, 2021 |
Journal | International Journal of Molecular Sciences |
Print ISSN | 1661-6596 |
Electronic ISSN | 1422-0067 |
Publisher | MDPI |
Peer Reviewed | Peer Reviewed |
Volume | 22 |
Issue | 8 |
Article Number | 4232 |
DOI | https://doi.org/10.3390/ijms22084232 |
Keywords | Inorganic Chemistry; Organic Chemistry; Physical and Theoretical Chemistry; Computer Science Applications; Spectroscopy; Molecular Biology; General Medicine; Catalysis |
Public URL | https://nottingham-repository.worktribe.com/output/6738693 |
Publisher URL | https://www.mdpi.com/1422-0067/22/8/4232/htm |
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Systematic Assessment of Chemokine Signaling at Chemokine Receptors CCR4, CCR7 and CCR10
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Publisher Licence URL
https://creativecommons.org/licenses/by/4.0/
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