ArticleCancer science2009
Ligand-independent higher-order multimerization of CXCR4, a G-protein-coupled chemokine receptor involved in targeted metastasis.
Article in Cancer science, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed.
- CXCR4 mediated recognition of HIV envelope spike and inhibition by CXCL12.Nature communications · 2025Article
- Structural insights into CXCR4 modulation and oligomerization.Nature structural & molecular biology · 2025Article
- A homotrimeric GPCR architecture of the human cytomegalovirus revealed by cryo-EM.Cell discovery · 2024Article
- The β2-adrenergic receptor associates with CXCR4 multimers in human cancer cells.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Dynamic Dimerization of Chemokine Receptors and Potential Inhibitory Role of Their Truncated Isoforms Revealed through Combinatorial Prediction.International journal of molecular sciences · 2023Article
- Strategies for Site-Specific Labeling of Receptor Proteins on the Surfaces of Living Cells by Using Genetically Encoded Peptide Tags.Chembiochem : a European journal of chemical biology · 2021Review
- Precision engineering of targeted nanocarriers.Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology · 2018Review
- Closely related, yet unique: Distinct homo- and heterodimerization patterns of G protein coupled chemokine receptors and their fine-tuning by cholesterol.PLoS computational biology · 2018Article
- Potential Role of Chemokines in Fracture Repair.Frontiers in endocrinology · 2017Review
- RP S19 C-terminal peptide trimer acts as a C5a receptor antagonist.Biochemistry and biophysics reports · 2016Article
- Diversity and Inter-Connections in the CXCR4 Chemokine Receptor/Ligand Family: Molecular Perspectives.Frontiers in immunology · 2015Review
- Optogenetic control of chemokine receptor signal and T-cell migration.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- The role of tyrosine sulfation in the dimerization of the CXCR4:SDF-1 complex.Protein science : a publication of the Protein Society · 2013Article
- Identification and profiling of CXCR3-CXCR4 chemokine receptor heteromer complexes.British journal of pharmacology · 2013Article
- Arrest Functions of the MIF Ligand/Receptor Axes in Atherogenesis.Frontiers in immunology · 2013Article
- Chemokine receptor oligomerization and allostery.Progress in molecular biology and translational science · 2013Review
- Drug discovery research targeting the CXC chemokine receptor 4 (CXCR4).Journal of medicinal chemistry · 2012Review
- The level of CD147 expression correlates with cyclophilin-induced signalling and chemotaxis.BMC research notes · 2011Article
- Improvement of lentiviral vector-mediated gene transduction by genetic engineering of the structural protein Pr55 Gag.Gene therapy · 2010Article
- Hetero-oligomerization of CCR2, CCR5, and CXCR4 and the protean effects of "selective" antagonists.The Journal of biological chemistry · 2009Article
Corrections and comments
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Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
CXCR4, a G-protein-coupled receptor of CXCL12/stromal cell-derived factor-1alpha, mediates a wide range of physiological and pathological processes, including the targeted metastasis of cancer cells. CXCR4 has been shown to homo-oligomerize in several experimental systems. However, it remains unclear with which domains CXCR4 interacts homotypically, and whether it dimerizes or forms a higher-order complex. To address these issues, we used bioluminescent resonance energy transfer and bimolecular fluorescence complementation analyses to measure the homotypic interactions of CXCR4 in living cells. Both assays indicated that CXCR4 interacts homotypically, which is consistent with previous studies. By studying CXCR4 mutants lacking various domains, we found that multiple transmembrane domains probably serve as potential molecular interaction surfaces for oligomerization. The relative contribution of the amino- or carboxy-termini to oligomerization was small. To differentiate between a dimer and a multimer consisting of more than two molecules, bioluminescent resonance energy transfer-bimolecular fluorescence complementation analysis was conducted. It revealed that CXCR4 engages in higher-order oligomerization in a ligand-independent fashion. This is the first report providing direct experimental evidence for the higher-order multimerization of CXCR4 in vivo. We hypothesize that CXCR4 distributes to the cell surface as a multimer, in order to effectively sense, with increased avidity, the chemotaxis-inducing ligand in the microenvironment. Studying the structure and function of the oligomeric state of CXCR4 may lead us to develop novel CXCR4 inhibitors that disassemble the molecular cluster of CXCR4.
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