ArticleThe Journal of biological chemistry2011
CXCR7/CXCR4 heterodimer constitutively recruits beta-arrestin to enhance cell migration.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 201 papers.
What it found
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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.
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Who cites it
201 citing papers in PubMed, 331 citations in OpenAlex.
- Induction of C-X-C chemokine receptor type 7 (CXCR7) switches stromal cell-derived factor-1 (SDF-1) signaling and phagocytic activity in macrophages linked to atherosclerosis.The Journal of biological chemistry · 2013Trial
- Stromal-Derived Factor-1 (SDF-1/CXCL12) and Skin Wound Healing Research at the Intersection Between Regenerative Biology and Medicine.International journal of molecular sciences · 2026Review
- The CXCL12-CXCR4 axis in colorectal cancer: immune regulation, metastatic progression, and therapeutic implications.Frontiers in immunology · 2026Review
- GPCR Heterodimers: Implications for Biased Signaling.Handbook of experimental pharmacology · 2026Review
- TR-FRET between engineered nanobodies reveals the existence of endogenous CXCR4 oligomers.Communications biology · 2025Article
- Human and viral chemokines differentially modulate G protein signaling, β-arrestin recruitment and chemotaxis mediated by the viral G protein-coupled receptor ORF74.Cell communication and signaling : CCS · 2025Article
- Ligand-Induced Biased Activation of GPCRs: Recent Advances and New Directions from In Silico Approaches.Molecules (Basel, Switzerland) · 2025Review
- ACKR3 agonism induces heterodimerization with chemokine receptor CXCR4 and attenuates platelet function.European journal of clinical investigation · 2025Article
- CXCL12 restricts tumor growth by suppressing the Ras, ERK1/2, c-Myc, and the immune checkpoint PD-L1 pathways.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- The cell adhesion molecule CD44 acts as a modulator of 5-HT7 receptor functions.Cell communication and signaling : CCS · 2024Article
- Atypical chemokine receptors in the immune system.Nature reviews. Immunology · 2024Review
- Article
- 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
- Crosstalk between purinergic receptor P2YCellular and molecular life sciences : CMLS · 2024Article
- CXCL12 impact on glioblastoma cells behaviors under dynamic culture conditions: Insights for developing new therapeutic approaches.PloS one · 2024Article
- Atypical Chemokine Receptor 3 "Senses" CXC Chemokine Receptor 4 Activation Through GPCR Kinase Phosphorylation.Molecular pharmacology · 2023Article
- LPA1-mediated inhibition of CXCR4 attenuates CXCL12-induced signaling and cell migration.Cell communication and signaling : CCS · 2023Article
- CXCR7 promotes the migration of fibroblasts derived from patients with acquired laryngotracheal stenosis by NF-κB signaling.Translational pediatrics · 2023Article
- Could Plasma CXCL12 Predict Ventricular Dysfunction in Patients with Severe Myocardial Infarction?The International journal of angiology : official publication of the International College of Angiology, Inc · 2023Article
- C-X-C chemokine receptor type 7 antibody enhances neural plasticity after ischemic stroke.Neural regeneration research · 2023Article
141 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
G protein-coupled receptor hetero-oligomerization is emerging as an important regulator of ligand-dependent transmembrane signaling, but precisely how receptor heteromers affect receptor pharmacology remains largely unknown. In this study, we have attempted to identify the functional significance of the heteromeric complex between CXCR4 and CXCR7 chemokine receptors. We demonstrate that co-expression of CXCR7 with CXCR4 results in constitutive recruitment of β-arrestin to the CXCR4·CXCR7 complex and simultaneous impairment of G(i)-mediated signaling. CXCR7/CXCR4 co-expression also results in potentiation of CXCL12 (SDF-1)-mediated downstream β-arrestin-dependent cell signaling pathways, including ERK1/2, p38 MAPK, and SAPK as judged from the results of experiments using siRNA knockdown to deplete β-arrestin. Interestingly, CXCR7/CXCR4 co-expression enhances cell migration in response to CXCL12 stimulation. Again, inhibition of β-arrestin using either siRNA knockdown or a dominant negative mutant abrogates the enhanced CXCL12-dependent migration of CXCR4/CXCR7-expressing cells. These results show how CXCR7, which cannot signal directly through G protein-linked pathways, can nevertheless affect cellular signaling networks by forming a heteromeric complex with CXCR4. The CXCR4·CXCR7 heterodimer complex recruits β-arrestin, resulting in preferential activation of β-arrestin-linked signaling pathways over canonical G protein pathways. CXCL12-dependent signaling of CXCR4 and its role in cellular physiology, including cancer metastasis, should be evaluated in the context of potential functional hetero-oligomerization with CXCR7.
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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.