ArticlePloS one2017
The DRF motif of CXCR6 as chemokine receptor adaptation to adhesion.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 33 citations in OpenAlex.
- Glycolysis-driven cancer-associated fibroblasts shape T-Cell exclusion via the CXCL16-CXCR6 Axis: a metabolic-chemokine mechanism in tumor immunity.Journal of translational medicine · 2026Review
- Nasal CD4+ tissue-resident memory T cells provide cross-protective immunity to influenza.The Journal of experimental medicine · 2026Article
- Modulation of Chemokine Activity for Enhanced Angiogenesis and Tissue Regeneration in Chronic Wounds.International journal of molecular sciences · 2026Review
- Inflammatory, clinical and sociodemographic factors associated with depressive disorder during pregnancy in Brazilian women.Scientific reports · 2026Article
- Evolutionary diversity of CXCL16-CXCR6: Convergent substitutions and recurrent gene loss in sauropsids.Immunogenetics · 2024Article
- Review
- C-C motif chemokine ligand 2 regulates prostaglandin synthesis and embryo attachment of the bovine endometrium during implantation.Cell and tissue research · 2024Article
- Review
- T cell receptor signaling strength establishes the chemotactic properties of effector CD8Nature communications · 2023Article
- Molecular and cellular mechanisms of inflammation in atherosclerosis.Frontiers in cardiovascular medicine · 2023Review
- Cryo-EM structure of G-protein-coupled receptor GPR17 in complex with inhibitory G protein.MedComm · 2022Article
- CXCR6-based immunotherapy in autoimmune, cancer and inflammatory infliction.Acta pharmaceutica Sinica. B · 2022Article
- Review
- CXCR6 expressing T cells: Functions and role in the control of tumors.Frontiers in immunology · 2022Review
- Article
- TM2D genes regulate Notch signaling and neuronal function in Drosophila.PLoS genetics · 2021Article
- CXCR6 by increasing retention of memory CD8Journal for immunotherapy of cancer · 2021Article
- Dendritic cells maintain anti-tumor immunity by positioning CD8 skin-resident memory T cells.Life science alliance · 2021Article
- Article
- Behavior of Chemokine Receptor 6 (CXCR6) in Complex with CXCL16 Soluble form Chemokine by Molecular Dynamic Simulations: General Protein‒Ligand Interaction Model and 3D-QSAR Studies of Synthetic Antagonists.Life (Basel, Switzerland) · 2021Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The CXC-chemokine receptor 6 (CXCR6) is a class A GTP-binding protein-coupled receptor (GPCRs) that mediates adhesion of leukocytes by interacting with the transmembrane cell surface-expressed chemokine ligand 16 (CXCL16), and also regulates leukocyte migration by interacting with the soluble shed variant of CXCL16. In contrast to virtually all other chemokine receptors with chemotactic activity, CXCR6 carries a DRF motif instead of the typical DRY motif as a key element in receptor activation and G protein coupling. In this work, modeling analyses revealed that the phenylalanine F3.51 in CXCR6 might have impact on intramolecular interactions including hydrogen bonds by this possibly changing receptor function. Initial investigations with embryonic kidney HEK293 cells and further studies with monocytic THP-1 cells showed that mutation of DRF into DRY does not influence ligand binding, receptor internalization, receptor recycling, and protein kinase B (AKT) signaling. Adhesion was slightly decreased in a time-dependent manner. However, CXCL16-induced calcium signaling and migration were increased. Vice versa, when the DRY motif of the related receptor CX3CR1 was mutated into DRF the migratory response towards CX3CL1 was diminished, indicating that the presence of a DRF motif generally impairs chemotaxis in chemokine receptors. Transmembrane and soluble CXCL16 play divergent roles in homeostasis, inflammation, and cancer, which can be beneficial or detrimental. Therefore, the DRF motif of CXCR6 may display a receptor adaptation allowing adhesion and cell retention by transmembrane CXCL16 but reducing the chemotactic response to soluble CXCL16. This adaptation may avoid permanent or uncontrolled recruitment of inflammatory cells as well as cancer metastasis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.