ArticleCell communication and signaling : CCS2025
GPR15LG binds CXCR4 and synergistically modulates CXCL12-induced cell signaling and migration.
Article in Cell communication and signaling : CCS, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed.
- International Union of Basic and Clinical Pharmacology. CXXII. Applying an objective evaluation to the status of class A orphan G protein-coupled receptors.Pharmacological reviews · 2026Review
- hucMSCs alleviate LPS-induced endothelial glycocalyx damage by secreting Cxcl12 to activate CXCR4.Stem cell research & therapy · 2026Article
- Decoding Neuroinflammatory Pathways: The Role of the CXCL12-CXCR4/CXCR7 Axis in ALS-Related Cognitive Impairment.Molecular neurobiology · 2026Review
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Authors and funding
24 authors.
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Abstract
backgroundGPR15LG, a chemokine-like ligand for the G-protein coupled receptor 15 (GPR15), is abundantly expressed in the gastrointestinal mucosa and inflamed skin. Emerging evidence suggests its involvement in inflammatory disorders and cancers. C-X-C chemokine receptor type 4 (CXCR4) plays a critical role in immune cell trafficking and cancer metastasis. Recent evidence suggests a connection between GPR15LG and CXCR4 signaling, which has not been investigated so far.
methodsWe investigated the effects of GPR15LG on CXCR4 signaling and downstream functions. Binding assays and computational modeling were performed to assess the interaction between GPR15LG and CXCR4. Functional assays, including wound healing and cell migration assays, were conducted across various cell types, including CD4⁺ T cells and cancer cells, to evaluate the impact of GPR15LG on CXCL12-mediated CXCR4 signaling.
resultsThe results demonstrate that GPR15LG binds to the orthosteric site of CXCR4, modulating downstream signaling in a context-dependent manner. Specifically, GPR15LG enhances CXCL12-mediated CXCR4 signaling synergistically, promoting wound healing and cell migration across various cell types, including CD4 + T cells and cancer cells.
conclusionsThese findings underscore the role of GPR15LG in inflammation and metastasis, offering potential therapeutic avenues for CXCR4-mediated diseases.
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