ArticleThe Journal of biological chemistry2009
Hetero-oligomerization of CCR2, CCR5, and CXCR4 and the protean effects of "selective" antagonists.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 96 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
96 citing papers in PubMed, 160 citations in OpenAlex.
- Cellular context and ligand class shape CXCR4-CCR5 heteromerization in live cells.Research square · 2026Article
- Pharmacological modulation of CXCL12/CXCR4/ACKR3 for brain disorders - an overview.Cell communication and signaling : CCS · 2026Review
- GPCR Heterodimers: Implications for Biased Signaling.Handbook of experimental pharmacology · 2026Review
- Targeting of specific CCR5-G protein complexes underlies biased signaling by HIV-1 envelope glycoproteins.Cell communication and signaling : CCS · 2025Article
- Regulation of CXCR4 function by S1PCell communication and signaling : CCS · 2025Article
- Structural insights into CXCR4 modulation and oligomerization.Nature structural & molecular biology · 2025Article
- CCR2 cooperativity promotes hematopoietic stem cell homing to the bone marrow.Science advances · 2024Article
- Dynamic Dimerization of Chemokine Receptors and Potential Inhibitory Role of Their Truncated Isoforms Revealed through Combinatorial Prediction.International journal of molecular sciences · 2023Article
- LPA1-mediated inhibition of CXCR4 attenuates CXCL12-induced signaling and cell migration.Cell communication and signaling : CCS · 2023Article
- Cytomegalovirus and Cardiovascular Disease: A Hypothetical Role for Viral G-Protein-Coupled Receptors in Hypertension.American journal of hypertension · 2023Review
- G protein activation via chemokine (C-X-C motif) receptor 4 and αFEBS letters · 2023Article
- Multiple mechanisms of self-association of chemokine receptors CXCR4 and CCR5 demonstrated by deep mutagenesis.bioRxiv : the preprint server for biology · 2023Article
- Review
- C-C chemokine receptor 5 and acute graft-versus-host disease.Immunity, inflammation and disease · 2022Review
- Article
- ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production.Frontiers in immunology · 2022Article
- The marriage of chemokines and galectins as functional heterodimers.Cellular and molecular life sciences : CMLS · 2021Review
- Co-receptor signaling in the pathogenesis of neuroHIV.Retrovirology · 2021Review
- Class A G protein-coupled receptors assemble into functional higher-order hetero-oligomers.FEBS letters · 2021Article
- Article
36 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
Chemokine receptors constitute an attractive family of drug targets in the frame of inflammatory diseases. However, targeting specific chemokine receptors may be complicated by their ability to form dimers or higher order oligomers. Using a combination of luminescence complementation and bioluminescence resonance energy transfer assays, we demonstrate for the first time the existence of hetero-oligomeric complexes composed of at least three chemokine receptors (CCR2, CCR5, and CXCR4). We show in T cells and monocytes that negative binding cooperativity takes place between the binding pockets of these receptors, demonstrating their functional interaction in leukocytes. We also show that specific antagonists of one receptor (TAK-779 or AMD3100) lead to functional cross-inhibition of the others. Finally, using the air pouch model in mice, we show that the CCR2 and CCR5 antagonist TAK-779 inhibits cell recruitment promoted by the CXCR4 agonist SDF-1 alpha, demonstrating that cross-inhibition by antagonists also occurs in vivo. Thus, antagonists of the therapeutically important chemokine receptors regulate the functional properties of other receptors to which they do not bind directly with important implications for the use of these agents in vivo.
Indexed as
Identifiers
What OpenQuestion holds
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.