Affinage

ACKR3

Atypical chemokine receptor 3 · UniProt P25106

Length
362 aa
Mass
41.5 kDa
Annotated
2026-04-28
100 papers in source corpus 30 papers cited in narrative 28 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ACKR3 (CXCR7) is an atypical chemokine receptor that functions primarily as a ligand scavenger and biased signaling receptor, regulating the bioavailability of chemokines (CXCL12, CXCL11), adrenomedullin-family peptides, and opioid peptides for their cognate classical receptors (PMID:16107333, PMID:25203207, PMID:32561830). ACKR3 does not couple to G proteins but signals through β-arrestin recruitment—driven by GRK2/3/5/6-mediated C-tail phosphorylation—to activate ERK1/2 and AKT pathways, and undergoes constitutive dynamin-dependent internalization and recycling that underpins its scavenging function (PMID:37558722, PMID:22300987, PMID:33799570). It forms constitutive heterodimers with CXCR4, modulating CXCR4-dependent Gαi signaling and calcium responses, and regulates plasma CXCL12 levels through endothelial scavenging to shape leukocyte migration, cortical interneuron positioning, oligodendrocyte maturation, and cardiac valve development (PMID:19380869, PMID:24116850, PMID:30726732, PMID:21246655). In platelets, ACKR3 agonism shifts lipid metabolism toward antithrombotic mediators (12-HETrE) that engage a cAMP/PKA inhibitory pathway, suppressing platelet activation and thrombosis (PMID:35383158, PMID:34905596).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 2005 High

    The orphan receptor RDC1 was identified as a second high-affinity CXCL12 receptor (renamed CXCR7), resolving whether CXCR4 was the sole receptor for this chemokine and opening the question of how two receptors partition CXCL12 signaling.

    Evidence Radioligand binding, chemotaxis, and internalization assays in CXCR4-negative T cells

    PMID:16107333

    Open questions at the time
    • Whether CXCR7 signals through canonical G-protein pathways was untested
    • Physiological role in vivo unknown
  2. 2009 High

    CXCR7 was shown to heterodimerize constitutively with CXCR4 and to attenuate CXCR4-Gαi coupling and calcium signaling, establishing that CXCR7 modulates CXCL12 responses indirectly through receptor–receptor interactions rather than canonical G-protein signaling.

    Evidence BRET/FRET dimerization assays, G-protein activation and calcium flux assays in co-expressing cells and primary T cells

    PMID:19380869

    Open questions at the time
    • Signaling pathway downstream of CXCR7 itself unresolved
    • Scavenging capacity versus CXCR4 not directly compared
  3. 2009 Medium

    Quantitative comparison showed CXCR7 accumulates more cell-associated CXCL12 than CXCR4, supporting a predominant scavenger function.

    Evidence Bioluminescent CXCL12-Gaussia luciferase uptake assay

    PMID:19594447

    Open questions at the time
    • Single assay system without in vivo validation
    • Internalization kinetics and recycling not characterized
  4. 2011 Medium

    Genetic deletion revealed CXCR7 is required for semilunar cardiac valve development, with loss-of-function causing valve stenosis and elevated BMP signaling, establishing the first in vivo developmental requirement.

    Evidence Germline and Tie2-Cre endocardial-specific Cxcr7 knockout mice with phospho-Smad1/5/8 immunostaining

    PMID:21246655

    Open questions at the time
    • BMP pathway link is correlative—direct molecular mechanism connecting CXCR7 to Smad1/5/8 undefined
    • Ligand mediating valve phenotype unidentified
  5. 2012 High

    The C-terminal tail was defined as the molecular determinant controlling CXCR7 constitutive internalization, β-arrestin-2 recruitment, ERK activation, ubiquitination-dependent trafficking, and chemokine scavenging, establishing β-arrestin-biased signaling as the principal transduction mechanism.

    Evidence C-tail deletion/point mutants, ubiquitination assays, dynamin inhibition, β-arrestin depletion, ERK phosphorylation, and CXCL12 scavenging assays

    PMID:22300987 PMID:22457824

    Open questions at the time
    • Specific phosphorylation sites and responsible kinases not yet mapped
    • Whether β-arrestin is essential or dispensable for internalization unclear
  6. 2014 High

    Genetic epistasis demonstrated that CXCR7 scavenges adrenomedullin in addition to CXCL12, establishing it as a multi-ligand decoy receptor controlling cardiac and lymphatic vascular development through ligand removal rather than signal transduction.

    Evidence Cxcr7−/− and Cxcr7−/−;Adm+/− double-knockout rescue in mice with cardiac/lymphatic phenotyping

    PMID:25203207

    Open questions at the time
    • Structural basis for adrenomedullin binding versus CXCL12 binding unknown
    • Whether adrenomedullin scavenging occurs in adult tissues untested
  7. 2014 High

    CXCR7 was placed in neural circuit development: endothelial CXCR7 controls plasma CXCL12 gradients for leukocyte migration, while neuronal CXCR7 directs cortical interneuron laminar positioning under Lhx6 transcriptional control, broadening its physiological scope beyond vascular biology.

    Evidence CXCR7 knockout mice with plasma CXCL12 ELISA, CXCR7-lacZ reporter immunohistochemistry; ChIP for Lhx6 at CXCR7 enhancer, MGE transplantation rescue in Lhx6−/− mice

    PMID:24116850 PMID:24742460

    Open questions at the time
    • Whether scavenging or signaling mediates interneuron guidance not dissected
    • Other transcriptional regulators of CXCR7 in neurons unknown
  8. 2014 Medium

    CXCR7 was found to interact with EGFR via β-arrestin-2 scaffolding, enhancing EGFR phosphorylation and ERK signaling in breast cancer, revealing a crosstalk mechanism with receptor tyrosine kinases.

    Evidence Proximity ligation assay for CXCR7-EGFR, siRNA knockdown of CXCR7 and β-arrestin-2, phospho-EGFR/ERK Western blots

    PMID:25168820

    Open questions at the time
    • Direct versus indirect interaction not resolved
    • Whether EGFR crosstalk occurs in non-cancer contexts unknown
  9. 2016 Medium

    HHV-8 vCCL2 was identified as a high-affinity viral partial agonist of ACKR3 that triggers β-arrestin recruitment and receptor internalization, demonstrating viral exploitation of the scavenging pathway.

    Evidence β-arrestin recruitment, receptor surface quantification, endosomal trafficking, and signaling assays

    PMID:27238288

    Open questions at the time
    • In vivo relevance during HHV-8 infection not tested
    • Structural basis for partial agonism unknown
  10. 2019 High

    Phosphorylation-deficient ACKR3 knock-in mice dissociated phosphorylation from β-arrestin dependence in vivo: C-tail phosphorylation is essential for CXCL12 scavenging and interneuron migration, whereas β-arrestin is dispensable, clarifying the minimal signal required for physiological scavenging.

    Evidence Phospho-deficient and β-arrestin-KO knock-in mice with in vivo interneuron migration, CXCL12 levels, and CXCR4 degradation assays

    PMID:30726732

    Open questions at the time
    • Identity of the kinase(s) responsible for in vivo phosphorylation not resolved in this study
    • Alternative internalization pathways not characterized
  11. 2020 High

    ACKR3 was established as a broad-spectrum opioid peptide scavenger, extending its ligand repertoire beyond chemokines and peptide hormones and positioning it as a regulator of endogenous opioid tone.

    Evidence Radioligand binding, β-arrestin recruitment, in vitro scavenging assays, ex vivo rat brain pharmacology with ACKR3-selective competitor LIH383

    PMID:32561830

    Open questions at the time
    • In vivo behavioral consequences of ACKR3 opioid scavenging not shown
    • Whether opioid scavenging involves distinct internalization trafficking from chemokine scavenging unknown
  12. 2021 Medium

    Fine-mapping of the ACKR3 C-tail identified T352/S355 as the critical phosphorylation cluster for β-arrestin-1 recruitment, with GRK2/3 as the responsible kinases, and demonstrated that ACKR3 can internalize via β-arrestin-independent pathways.

    Evidence BRET/FRET sensors, phosphosite mutagenesis, GRK co-expression/knockdown in HEK293T cells

    PMID:33799570

    Open questions at the time
    • In vivo relevance of individual phosphosites not tested
    • Identity of β-arrestin-independent internalization pathway not determined
  13. 2022 High

    Platelet-specific ACKR3 deletion revealed a novel antithrombotic axis: ACKR3 agonism shifts platelet lipid metabolism toward 12-HETrE (from DGLA), which cooperates with prostacyclin receptor/Gαs to activate cAMP/PKA-dependent platelet inhibition, connecting ACKR3 to hemostasis.

    Evidence Megakaryocyte/platelet-specific Ackr3 conditional knockout mice, in vivo thrombosis and ischemia-reperfusion models, targeted lipidomics

    PMID:34905596 PMID:35383158

    Open questions at the time
    • How ACKR3 engagement alters lipid enzyme activity is unknown
    • Whether platelet ACKR3 also scavenges chemokines in the hemostatic context not addressed
  14. 2023 High

    Comprehensive transducer profiling confirmed ACKR3 is fully uncoupled from all G proteins while engaging β-arrestin predominantly via GRK5/6, and showed that CXCL12-activated ACKR3 and CXCR4 induce distinct β-arrestin conformations, explaining divergent downstream signaling from the same ligand.

    Evidence Full transducer-coupling panel, β-arrestin conformation BRET sensors, GRK isoform-specific assays, phosphosite mutagenesis in HEK293 cells

    PMID:37558722

    Open questions at the time
    • Structural basis of distinct β-arrestin conformations not solved
    • Downstream effectors of ACKR3-specific β-arrestin conformation unidentified

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis for ACKR3's multi-ligand promiscuity (chemokines, adrenomedullin, opioids), the identity and regulation of β-arrestin-independent internalization pathways, the mechanism by which ACKR3 reprograms platelet lipid metabolism, and whether ACKR3 opioid scavenging modulates pain or addiction behaviors in vivo.
  • No high-resolution structure of ACKR3 with a non-chemokine ligand
  • β-arrestin-independent internalization pathway identity unknown
  • In vivo behavioral role of opioid scavenging untested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0038024 cargo receptor activity 6 GO:0060089 molecular transducer activity 3 GO:0098772 molecular function regulator activity 3
Localization
GO:0005768 endosome 4 GO:0005886 plasma membrane 4 GO:0031410 cytoplasmic vesicle 2
Pathway
R-HSA-162582 Signal Transduction 6 R-HSA-1266738 Developmental Biology 4 R-HSA-168256 Immune System 2 R-HSA-109582 Hemostasis 1
Partners
ARRB1ARRB2CXCR4EGFRGRK2GRK3GRK5GRK6
Complex memberships
CXCR4/ACKR3 heterodimer

Evidence

Reading pass · 28 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2005 CXCL12/SDF-1 binds to and signals through RDC1 (renamed CXCR7/ACKR3) with high affinity (apparent KD ~0.4 nM), promoting receptor internalization and chemotactic signals in CXCR4-negative cells expressing RDC1, establishing RDC1 as a bona fide CXCL12 receptor in T lymphocytes. Radioligand binding assay, chemotaxis assay with anti-RDC1 antibody blockade, receptor internalization assay in CXCR4-negative cells The Journal of biological chemistry High 16107333
2009 CXCR7 forms constitutive heterodimers with CXCR4 (as efficiently as homodimers), does not itself trigger Gαi-protein-dependent signaling despite constitutive interaction with Gαi proteins, and impairs CXCR4-promoted Gαi-protein activation and calcium responses when co-expressed, identifying CXCR4/CXCR7 heterodimers as distinct functional units that modulate CXCL12 signaling. BRET/FRET energy transfer assays for protein–protein interactions, G protein signaling assays, calcium flux assays, primary T cell co-expression studies Blood High 19380869
2012 CXCR7 is constitutively ubiquitinated, and this ubiquitination is required for correct trafficking from and to the plasma membrane; CXCL12 treatment causes reversible de-ubiquitination. Internalization depends on both β-arrestin and Ser/Thr residues at the C-terminus, and C-terminal Lys residues are essential for surface delivery. Mutagenesis of C-terminal Ser/Thr and Lys residues, ubiquitination assays, internalization/recycling assays, β-arrestin depletion PloS one High 22457824
2012 The C-terminal intracellular tail of CXCR7 controls receptor localization (wild-type receptor localizes predominantly to intracellular vesicles), constitutive internalization, ligand-dependent β-arrestin-2 recruitment, chemokine scavenging, and CXCL12-stimulated ERK1/2 activation; dynamin-dependent internalization facilitates β-arrestin-2 association and ERK1/2 signaling. Carboxy-terminus deletion mutants, firefly luciferase complementation for β-arrestin-2 recruitment, dynamin inhibition, ERK1/2 phosphorylation assays, CXCL12 scavenging assays The international journal of biochemistry & cell biology High 22300987
2014 CXCR7 acts as a decoy/scavenger receptor for adrenomedullin (AM), controlling AM bioavailability and downstream GPCR-mediated cardiac and lymphatic vascular development; Cxcr7−/− mice show gain-of-function cardiac and lymphatic phenotypes rescued by genetic depletion of the adrenomedullin ligand. Genetic mouse knockout (Cxcr7−/−), adrenomedullin ligand double-knockout rescue epistasis, cardiac/lymphatic phenotyping Developmental cell High 25203207
2019 ACKR3 phosphorylation (but not β-arrestin) is essential for its function as a CXCL12 scavenger controlling interneuron migration; phosphorylation-deficient ACKR3 mice exhibit major interneuron migration defects accompanied by excess CXCL12, lysosomal CXCR4 degradation, and loss of CXCR4 responsiveness, demonstrating that ACKR3 sequesters CXCL12 to prevent over-activation and subsequent loss of CXCR4. Phosphorylation-deficient and β-arrestin-deficient knock-in mice, in vivo interneuron migration assays, CXCL12 level measurements, CXCR4 degradation assays Cell reports High 30726732
2020 ACKR3/CXCR7 is a broad-spectrum scavenger receptor for opioid peptides (especially enkephalins and dynorphins), functioning as a negative regulator of opioid peptide availability for classical opioid receptors; an ACKR3-selective competitor peptide (LIH383) potentiates opioid peptide activity toward classical receptors in rat brain. Radioligand binding, β-arrestin recruitment assays, in vitro scavenging assays, rat brain ex vivo pharmacology with LIH383 competitor peptide Nature communications High 32561830
2014 Endothelial CXCR7 regulates circulating CXCL12 levels; genetic deletion or pharmacological inhibition of CXCR7 causes pronounced increases in plasma CXCL12 and impairs leukocyte migration toward local CXCL12 sources; CXCR7 protein is expressed primarily on venule endothelium and arteriole smooth muscle cells in humans and mice. CXCR7 genetic knockout mice, pharmacological inhibition, ELISA for plasma CXCL12, competitive binding assay, flow cytometry, immunohistochemistry with CXCR7+/lacZ reporter mice Immunology High 24116850
2019 CXCR7 activates MAPK/ERK signaling through β-arrestin 2-dependent, ligand-independent mechanisms in prostate cancer, driving enzalutamide resistance; AR directly represses CXCR7 by binding an enhancer 110 kb downstream of the gene. Transcriptome analysis, ChIP assay for AR binding, β-arrestin 2 depletion, ERK phosphorylation assays, in vitro and in vivo CRPC growth assays, patient specimen analysis Cancer research High 30952632
2009 CXCR7 increases cell-associated CXCL12 to a significantly greater extent than CXCR4, consistent with a scavenging/internalization function; CXCL12 fused to Gaussia luciferase activates CXCR4-dependent signaling comparably to unfused CXCL12. Bioluminescent CXCL12-Gaussia luciferase fusion protein binding assay, multiwell plate chemokine uptake quantification, CXCR4 signaling assays BioTechniques Medium 19594447
2011 CXCR7 is required for semilunar cardiac valve development; Cxcr7 germline deletion causes aortic and pulmonary valve stenosis with increased mesenchymal cell proliferation and elevated phospho-Smad1/5/8 (BMP signaling); Tie2-Cre conditional knockout recapitulates the phenotype, implicating endocardial cell CXCR7 function. Germline and Tie2-Cre conditional knockout mice, histological phenotyping, phospho-Smad1/5/8 immunostaining Developmental dynamics Medium 21246655
2013 CXCR7 participates in CXCL12-induced cycling and survival of human CD34+ hematopoietic stem/progenitor cells via β-arrestin 2-dependent Akt activation; β-arrestin 2 translocates to the nucleus after CXCL12 treatment in a manner requiring both CXCR7 and CXCR4, and β-arrestin silencing reduces Akt activation. CXCR7 blocking antibody, β-arrestin 2 colocalization/nuclear translocation imaging, siRNA silencing of β-arrestins, Akt phosphorylation assays, colony formation and cell cycle assays in primary human CD34+ cells Blood Medium 24277075
2014 Lhx6 transcription factor directly binds an intronic CXCR7 enhancer in vivo, and CXCR7 regulates laminar positioning of MGE-derived cortical interneurons in neonatal cortex, as shown by MGE complementation/transplantation rescue assays. ChIP for Lhx6 binding at CXCR7 enhancer, in vivo MGE complementation/transplantation assay, interneuron lamination phenotyping in Lhx6−/− mice Neuron Medium 24742460
2014 Dickkopf-3 (Dkk3) physically binds CXCR7 with high affinity (Kd ~14 nmol/L) and triggers ERK1/2, PI3K/AKT, Rac1, and RhoA signaling to drive vascular progenitor cell migration; CXCR7 blocking antibodies impair stem/progenitor cell recruitment into tissue-engineered vessel grafts. Co-immunoprecipitation, saturation binding assay, overexpression/knockdown functional migration assays, in vivo tissue-engineered vessel graft model with CXCR7 antibody blockade Circulation research Medium 29980568
2016 HHV-8-encoded vCCL2/vMIP-II is a high-affinity ligand for ACKR3, acting as a partial agonist that induces β-arrestin recruitment, reduces surface ACKR3 levels, delivers receptor to endosomes, and reduces vCCL2-triggered MAP kinase and PI3K/Akt signaling through other chemokine receptors. β-arrestin recruitment assay, receptor surface level measurement by flow cytometry, endosomal trafficking imaging, MAP kinase and PI3K/Akt signaling assays Biochemical pharmacology Medium 27238288
2021 A single cluster of phosphorylated residues on the ACKR3 C-tail (particularly T352 and S355) determines β-arrestin1 recruitment; GRK2 and GRK3 phosphorylate ACKR3 and are key for β-arrestin recruitment and receptor internalization; ACKR3 can internalize independently of β-arrestins via alternative pathways; upon activation ACKR3 internalizes and recycles to the cell membrane. BRET/FRET-based sensors in HEK293T cells, phosphorylation site mutagenesis, GRK co-expression/knockdown, receptor internalization and trafficking assays Cells Medium 33799570
2023 CXCR7 lacks G-protein coupling while maintaining robust β-arrestin recruitment (predominantly via GRK5/6); CXCR7 and CXCR4 induce distinct β-arrestin conformations when activated by the same agonist CXCL12; CXCR7, unlike CXCR4, fails to activate ERK1/2 MAP kinase; a single phosphorylation site on CXCR7 is key for β-arrestin recruitment and endosomal localization. Comprehensive transducer-coupling characterization, βarr conformation BRET sensors, GRK isoform-specific assays, phosphorylation site mutagenesis, ERK1/2 assays Nature communications High 37558722
2022 Megakaryocyte/platelet-specific deletion of ACKR3 enhances platelet activation and thrombosis in vitro and in vivo; ACKR3 ligation with specific agonists inhibits platelet activation, thrombus formation, and attenuates tissue injury in ischemic myocardium and brain; ACKR3 agonism favors antithrombotic lipids (DGLA, 12-HETrE) over prothrombotic lipids, and 12-HETrE coordinates with Gαs-coupled prostacyclin receptor to trigger cAMP/PKA-mediated platelet inhibition. Platelet-specific Ackr3 conditional knockout mice, in vitro platelet activation assays, in vivo thrombosis and ischemia-reperfusion models, targeted and untargeted lipidomics (micro-UHPLC-ESI-MS/MS) Nature communications / Blood High 34905596 35383158
2022 Arterial endothelial ACKR3 promotes atherosclerosis by mediating immune cell adhesion to vascular endothelium through MAPK (ERK1/2) and NF-κB p65 pathways; smooth muscle cell or hematopoietic ACKR3 deficiency does not impact atherosclerosis. Apoe−/− mice with endothelial- or smooth muscle cell-specific Ackr3 deletion, atherosclerosis quantification, adhesion molecule expression, ERK1/2 and NF-κB p65 phosphorylation assays, ACKR3 silencing in human coronary artery endothelial cells Basic research in cardiology Medium 35674847
2021 PAMP-12 (proadrenomedullin N-terminal 20 peptide processed form) is a high-potency agonist for ACKR3, inducing β-arrestin recruitment and efficient receptor internalization without activating G protein or ERK signaling, identifying ACKR3 as a regulator of PAMP-12 availability for its primary receptor MrgX2. β-arrestin recruitment assay, G protein signaling assay, ERK assay, receptor internalization assay, comparison with ADM and CGRP family members with/without RAMPs ACS pharmacology & translational science Medium 33860204
2019 CXCR7 activates MAPK-ERK signaling via β-arrestin (not G-protein) to drive acquired resistance to EGFR TKIs in NSCLC; depletion of CXCR7 inhibits the MAPK pathway, attenuates EGFR TKI resistance, and induces mesenchymal-to-epithelial transition. CXCR7 depletion by siRNA/shRNA, ERK phosphorylation assays, EGFR TKI resistance models in vitro, patient specimen CXCR7 expression analysis Cancer research Medium 31273063
2018 MIF (macrophage migration inhibitory factor) is identified as a ligand for CXCR7, activating AKT signaling and inducing cell-cycle gene expression; AR directly represses CXCR7 expression (shown by CRISPR/Cas9 editing); the MIF/CXCR7/AKT pathway drives CRPC growth independent of CXCL12/CXCR4. CRISPR/Cas9-mediated AR binding site deletion, ligand binding assay for MIF-CXCR7, AKT phosphorylation assays, gene expression profiling, in vivo xenograft studies Molecular cancer research Medium 30224544
2016 CXCR7 transactivates EGFR in a β-arrestin-2-independent (G-protein-independent) manner; β-arrestin-2 acts as a negative regulator (tumor suppressor) of CXCR7/Src/EGFR-mediated mitogenic signaling; β-arrestin-2 depletion increases Src phosphorylation, EGFR Tyr-1110 phosphorylation, ERK1/2 activation, and nuclear EGFR translocation. β-arrestin-2 shRNA knockdown, cDNA knock-in, proximity ligation assay for CXCR7-EGFR colocalization, phosphorylation assays (Src, EGFR, ERK1/2, Akt), nuclear EGFR translocation imaging Molecular cancer research Medium 26921391
2014 CXCR7 interacts with EGFR in breast cancer cells, and β-arrestin-2 acts as a scaffold to enhance CXCR7-dependent activation of EGFR after EGF stimulation; CXCR7 depletion reduces EGFR phosphorylation at Tyr1110 and ERK1/2 phosphorylation. In situ proximity ligation assay (PLA) for CXCR7-EGFR colocalization in cancer tissues/cells, siRNA knockdown of CXCR7 and β-arrestin2, Western blotting for phospho-EGFR and phospho-ERK1/2 Molecular cancer Medium 25168820
2019 CXCR7 promotes melanoma proliferation via β-arrestin2-dependent Src kinase phosphorylation; CXCR7-Src axis stimulates eIF4E phosphorylation, accelerating HIF-1α translation and VEGF secretion to drive angiogenesis. CXCR7 knockout, Src kinase inhibitor PP1, β-arrestin2 siRNA, eIF4E and HIF-1α western blotting, VEGF ELISA, in vivo xenograft Cell death & disease Medium 30804329
2014 CXCR7 promotes oligodendroglial precursor cell maturation and myelin expression via CXCL12 stimulation; pharmacological inhibition of CXCR7 blocks CXCL12-dependent oligodendrocyte maturation, while CXCR7 antagonism in vivo augments OPC proliferation and increases mature oligodendrocyte numbers in demyelinated lesions, requiring CXCR4 co-activation. Pharmacological CXCR7 inhibition in primary OPC cultures, CXCR7 antagonist in cuprizone demyelination model in vivo, phospho-S339-CXCR4 antibody, CXCR4 antagonist epistasis The Journal of experimental medicine / Annals of neurology Medium 21154415 24733828
2023 CXCR7 activates the Hippo/YAP axis via Gαq/11 and Rho GTPase signaling, causing YAP dephosphorylation and nuclear accumulation in gastric cancer; YAP in turn binds the CXCR7 promoter to transcriptionally upregulate CXCR7, forming a positive feedback loop. ChIP assay for YAP binding at CXCR7 promoter, Gαq/11 and Rho GTPase inhibition, YAP phosphorylation/localization assays, pharmacological CXCR7 inhibition (ACT-1004-1239), in vivo xenograft model Journal of experimental & clinical cancer research Medium 37950281
2017 TGF-β1 upregulates CXCR7 expression via Smad2/3-dependent signaling in endothelial cells; overexpressed CXCR7 attenuates TGF-β1-induced endothelial-to-mesenchymal transition by inhibiting the Jag1-Notch pathway. Smad2/3 inhibition, CXCR7 overexpression and knockdown in endothelial cells, EndMT marker assays, Jag1-Notch pathway analysis, in vivo mouse lung fibrosis model Molecular bioSystems Medium 28820530

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2005 The chemokine SDF-1/CXCL12 binds to and signals through the orphan receptor RDC1 in T lymphocytes. The Journal of biological chemistry 854 16107333
2010 CXCL12 / CXCR4 / CXCR7 chemokine axis and cancer progression. Cancer metastasis reviews 606 20839032
2009 CXCR7 heterodimerizes with CXCR4 and regulates CXCL12-mediated G protein signaling. Blood 506 19380869
2007 The role of CXCR7/RDC1 as a chemokine receptor for CXCL12/SDF-1 in prostate cancer. The Journal of biological chemistry 387 18057003
2011 CXCL12 (SDF1alpha)-CXCR4/CXCR7 pathway inhibition: an emerging sensitizer for anticancer therapies? Clinical cancer research : an official journal of the American Association for Cancer Research 342 21349998
2020 The Role of the CXCL12/CXCR4/CXCR7 Chemokine Axis in Cancer. Frontiers in pharmacology 240 33363463
2010 Hypoxic preconditioning advances CXCR4 and CXCR7 expression by activating HIF-1α in MSCs. Biochemical and biophysical research communications 206 20869949
2019 The CXCL12-CXCR4/CXCR7 axis as a mechanism of immune resistance in gastrointestinal malignancies. Seminars in cancer biology 194 31874281
2012 CXCR7 impact on CXCL12 biology and disease. Trends in molecular medicine 174 23153575
2023 CXCL12-CXCR4/CXCR7 Axis in Cancer: from Mechanisms to Clinical Applications. International journal of biological sciences 159 37497001
2010 Chemokine receptor CXCR7 regulates the invasion, angiogenesis and tumor growth of human hepatocellular carcinoma cells. Journal of experimental & clinical cancer research : CR 149 20380740
2019 The Role of the CXCL12/CXCR4/ACKR3 Axis in Autoimmune Diseases. Frontiers in endocrinology 131 31507535
2017 The Role of SDF-1/CXCR4/CXCR7 in Neuronal Regeneration after Cerebral Ischemia. Frontiers in neuroscience 106 29123467
2009 The role of stromal-derived factor-1--CXCR7 axis in development and cancer. European journal of pharmacology 104 19835865
2019 Activation of MAPK Signaling by CXCR7 Leads to Enzalutamide Resistance in Prostate Cancer. Cancer research 101 30952632
2014 Lhx6 directly regulates Arx and CXCR7 to determine cortical interneuron fate and laminar position. Neuron 100 24742460
2015 CXCR7 mediates TGFβ1-promoted EMT and tumor-initiating features in lung cancer. Oncogene 98 26212008
2020 The atypical chemokine receptor ACKR3/CXCR7 is a broad-spectrum scavenger for opioid peptides. Nature communications 97 32561830
2013 Involvement of CXCR4/CXCR7/CXCL12 Interactions in Inflammatory bowel disease. Theranostics 96 23382785
2012 Ubiquitination of CXCR7 controls receptor trafficking. PloS one 87 22457824
2012 An infernal trio: the chemokine CXCL12 and its receptors CXCR4 and CXCR7 in tumor biology. Annals of anatomy = Anatomischer Anzeiger : official organ of the Anatomische Gesellschaft 87 23279723
2014 Decoy receptor CXCR7 modulates adrenomedullin-mediated cardiac and lymphatic vascular development. Developmental cell 82 25203207
2021 CXCR4 and CXCR7 Signaling Pathways: A Focus on the Cross-Talk Between Cancer Cells and Tumor Microenvironment. Frontiers in oncology 79 33937018
2014 Endothelial expression of CXCR7 and the regulation of systemic CXCL12 levels. Immunology 77 24116850
2014 The chemokine receptor CXCR7 interacts with EGFR to promote breast cancer cell proliferation. Molecular cancer 77 25168820
2009 CXCL12, CXCR4 and CXCR7 expression in brain metastases. Cancer biology & therapy 72 19625779
2014 CXCR4 and CXCR7 transduce through mTOR in human renal cancer cells. Cell death & disease 71 24991762
2011 The chemokine receptor CXCR7 functions to regulate cardiac valve remodeling. Developmental dynamics : an official publication of the American Association of Anatomists 69 21246655
2014 Hypoxia differentially regulated CXCR4 and CXCR7 signaling in colon cancer. Molecular cancer 67 24629239
2010 CXCR7 protein is not expressed on human or mouse leukocytes. Journal of immunology (Baltimore, Md. : 1950) 67 20889540
2010 Activation of CXCR7 receptor promotes oligodendroglial cell maturation. Annals of neurology 67 21154415
2020 Relevance of the CXCR4/CXCR7-CXCL12 axis and its effect in pathophysiological conditions. Pharmacological research 65 32758634
2020 The CXCL12/CXCR4/ACKR3 Axis in the Tumor Microenvironment: Signaling, Crosstalk, and Therapeutic Targeting. Annual review of pharmacology and toxicology 65 32956018
2019 ACKR3 Regulation of Neuronal Migration Requires ACKR3 Phosphorylation, but Not β-Arrestin. Cell reports 65 30726732
2017 CXCL12 and CXCR7 are relevant targets to reverse cell adhesion-mediated drug resistance in multiple myeloma. British journal of haematology 65 28670693
2017 Biological/pathological functions of the CXCL12/CXCR4/CXCR7 axes in the pathogenesis of bladder cancer. International journal of clinical oncology 64 29022185
2015 CXCL12-CXCR7 axis is important for tumor endothelial cell angiogenic property. International journal of cancer 64 26100110
2015 Crosstalk between SDF-1/CXCR4 and SDF-1/CXCR7 in cardiac stem cell migration. Scientific reports 59 26578388
2019 FGFR3 deficiency enhances CXCL12-dependent chemotaxis of macrophages via upregulating CXCR7 and aggravates joint destruction in mice. Annals of the rheumatic diseases 56 31662319
2014 Targeting CXCR7/ACKR3 as a therapeutic strategy to promote remyelination in the adult central nervous system. The Journal of experimental medicine 56 24733828
2018 Multisystem multitasking by CXCL12 and its receptors CXCR4 and ACKR3. Cytokine 55 29398278
2012 CXCR7 expression is associated with disease-free and disease-specific survival in cervical cancer patients. British journal of cancer 55 22531719
2010 CXCR4 and CXCR7 regulate angiogenesis and CT26.WT tumor growth independent from SDF-1. International journal of cancer 55 19821487
2019 CXCR7 Reactivates ERK Signaling to Promote Resistance to EGFR Kinase Inhibitors in NSCLC. Cancer research 53 31273063
2009 Bioluminescent CXCL12 fusion protein for cellular studies of CXCR4 and CXCR7. BioTechniques 52 19594447
2018 A Chimeric Antibody against ACKR3/CXCR7 in Combination with TMZ Activates Immune Responses and Extends Survival in Mouse GBM Models. Molecular therapy : the journal of the American Society of Gene Therapy 51 29606504
2018 Emerging roles of atypical chemokine receptor 3 (ACKR3) in normal development and physiology. Cytokine 51 29903572
1998 Cloning and chromosomal mapping of an orphan chemokine receptor: mouse RDC1. Immunogenetics 51 9510554
2019 Modulators of CXCR4 and CXCR7/ACKR3 Function. Molecular pharmacology 50 31548340
2016 Expression and function of CXCL12/CXCR4/CXCR7 in thyroid cancer. International journal of oncology 48 27082011
2021 Role and implications of the CXCL12/CXCR4/CXCR7 axis in atherosclerosis: still a debate. Annals of medicine 46 34494495
2017 CXCR7 attenuates the TGF-β-induced endothelial-to-mesenchymal transition and pulmonary fibrosis. Molecular bioSystems 46 28820530
2013 CXCR7 is induced by hypoxia and mediates glioma cell migration towards SDF-1α. BMC cancer 44 23865743
2019 The Role of ACKR3 in Breast, Lung, and Brain Cancer. Molecular pharmacology 42 30745320
2011 Expression of the new CXCL12 receptor, CXCR7, in gliomas. Cancer biology & therapy 42 21084856
2022 ACKR3 regulates platelet activation and ischemia-reperfusion tissue injury. Nature communications 41 35383158
2018 Targeting the MIF/CXCR7/AKT Signaling Pathway in Castration-Resistant Prostate Cancer. Molecular cancer research : MCR 41 30224544
2008 Differential expression of RDC1/CXCR7 in the human placenta. Journal of clinical immunology 41 18956235
2015 Dual targeting of the chemokine receptors CXCR4 and ACKR3 with novel engineered chemokines. The Journal of biological chemistry 40 26216880
2014 The relevance of the chemokine receptor ACKR3/CXCR7 on CXCL12-mediated effects in cancers with a focus on virus-related cancers. Cytokine & growth factor reviews 40 24853339
2019 Antibodies Targeting Chemokine Receptors CXCR4 and ACKR3. Molecular pharmacology 39 31481460
2018 Binding of Dickkopf-3 to CXCR7 Enhances Vascular Progenitor Cell Migration and Degradable Graft Regeneration. Circulation research 39 29980568
2016 Drug Design Targeting the CXCR4/CXCR7/CXCL12 Pathway. Current topics in medicinal chemistry 39 26369824
2013 CXCR7 participates in CXCL12-induced CD34+ cell cycling through β-arrestin-dependent Akt activation. Blood 39 24277075
2022 Colorectal Cancer: The Contribution of CXCL12 and Its Receptors CXCR4 and CXCR7. Cancers 37 35406582
2016 Andrographolide inhibits prostate cancer by targeting cell cycle regulators, CXCR3 and CXCR7 chemokine receptors. Cell cycle (Georgetown, Tex.) 37 27029529
2015 Role of chemokine receptors CXCR4 and CXCR7 for platelet function. Biochemical Society transactions 37 26551719
2002 Fusion of RDC1 with HMGA2 in lipomas as the result of chromosome aberrations involving 2q35-37 and 12q13-15. International journal of oncology 37 12118328
2013 CXCR4 and CXCR7 form a functional receptor unit for SDF-1/CXCL12 in primary rodent microglia. Neuropathology and applied neurobiology 36 23289420
2012 Carboxy-terminus of CXCR7 regulates receptor localization and function. The international journal of biochemistry & cell biology 36 22300987
2011 The expression of CXCR4, CXCL12 and CXCR7 in malignant pleural mesothelioma. The Journal of pathology 36 21294125
2022 Platelet ACKR3/CXCR7 favors antiplatelet lipids over an atherothrombotic lipidome and regulates thromboinflammation. Blood 35 34905596
2016 Human herpesvirus 8-encoded chemokine vCCL2/vMIP-II is an agonist of the atypical chemokine receptor ACKR3/CXCR7. Biochemical pharmacology 35 27238288
2016 β-Arrestin-2 Counters CXCR7-Mediated EGFR Transactivation and Proliferation. Molecular cancer research : MCR 34 26921391
2020 Advances in CXCR7 Modulators. Pharmaceuticals (Basel, Switzerland) 33 32098047
2016 Drug design strategies focusing on the CXCR4/CXCR7/CXCL12 pathway in leukemia and lymphoma. Expert opinion on drug discovery 33 27598329
2014 CXCR7-dependent angiogenic mononuclear cell trafficking regulates tumor progression in multiple myeloma. Blood 33 25079359
2022 Endothelial ACKR3 drives atherosclerosis by promoting immune cell adhesion to vascular endothelium. Basic research in cardiology 32 35674847
2021 Differential Involvement of ACKR3 C-Tail in β-Arrestin Recruitment, Trafficking and Internalization. Cells 32 33799570
2022 Emerging Roles of the Atypical Chemokine Receptor 3 (ACKR3) in Cardiovascular Diseases. Frontiers in endocrinology 30 35846294
2017 CXCR7 regulates breast tumor metastasis and angiogenesis in vivo and in vitro. Molecular medicine reports 29 29257351
2021 Proadrenomedullin N-Terminal 20 Peptides (PAMPs) Are Agonists of the Chemokine Scavenger Receptor ACKR3/CXCR7. ACS pharmacology & translational science 28 33860204
2016 Targeted Imaging of the Atypical Chemokine Receptor 3 (ACKR3/CXCR7) in Human Cancer Xenografts. Journal of nuclear medicine : official publication, Society of Nuclear Medicine 28 26912435
2018 miR-539-5p inhibits experimental choroidal neovascularization by targeting CXCR7. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 27 29146732
2016 CXCR4/CXCL12/CXCR7 axis is functional in neuroendocrine tumors and signals on mTOR. Oncotarget 27 26934559
2019 CXCR7 promotes melanoma tumorigenesis via Src kinase signaling. Cell death & disease 26 30804329
2014 Atorvastatin inhibits CXCR7 induction to reduce macrophage migration. Biochemical pharmacology 26 24582769
2023 Molecular insights into intrinsic transducer-coupling bias in the CXCR4-CXCR7 system. Nature communications 25 37558722
2020 Functions of the CXCL12 Receptor ACKR3/CXCR7-What Has Been Perceived and What Has Been Overlooked. Molecular pharmacology 24 32883765
2023 Regulation of the Hippo/YAP axis by CXCR7 in the tumorigenesis of gastric cancer. Journal of experimental & clinical cancer research : CR 23 37950281
2018 CXCR7 participates in CXCL12-mediated migration and homing of leukemic and normal hematopoietic cells. Stem cell research & therapy 23 29433559
2014 The involvement of CXCR7 in modulating the progression of papillary thyroid carcinoma. The Journal of surgical research 23 24814201
2024 Crosstalk between CXCL12/CXCR4/ACKR3 and the STAT3 Pathway. Cells 22 38920657
2020 Overexpression of CXCR7 accelerates tumor growth and metastasis of lung cancer cells. Respiratory research 22 33129326
2018 Critical involvement of atypical chemokine receptor CXCR7 in allergic airway inflammation. Immunology 22 29250768
2016 Downregulation of CXCR7 inhibits proliferative capacity and stem cell-like properties in breast cancer stem cells. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 22 27460092
2020 Inhibition of CXCR4 and CXCR7 Is Protective in Acute Peritoneal Inflammation. Frontiers in immunology 21 32210974
2018 Characterization of a chimeric chemokine as a specific ligand for ACKR3. Journal of leukocyte biology 21 29601107
2014 Chemokine receptor CXCR7 is a functional receptor for CXCL12 in brain endothelial cells. PloS one 21 25084358
2020 CXCR4 or CXCR7 antagonists treat endometriosis by reducing bone marrow cell trafficking. Journal of cellular and molecular medicine 20 31904910