Affinage

EPHB2

Ephrin type-B receptor 2 · UniProt P29323

Length
1055 aa
Mass
117.5 kDa
Annotated
2026-06-09
100 papers in source corpus 41 papers cited in narrative 41 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

EphB2 is a transmembrane receptor tyrosine kinase that governs cell repulsion, axon guidance, synaptic function, and tissue patterning through ephrin-driven bidirectional signaling (PMID:15107857, PMID:18713744). Its catalytic activity is held in check by an autoinhibitory juxtamembrane segment that adopts a helical conformation distorting the kinase small lobe and blocking the activation segment; autophosphorylation of conserved juxtamembrane tyrosines (notably Y605/Y611) relieves this autoinhibition and creates phosphotyrosine docking sites for SH2-domain effectors including Src and the Abl/Arg non-receptor kinases (PMID:11572780, PMID:9632142, PMID:11494128). Ligand engagement occurs through a jellyroll beta-sandwich ligand-binding domain that binds ephrin-B ligands and, across subclass, ephrin-A5, with clustering above the dimer threshold determining repulsive signaling strength (PMID:9853759, PMID:15107857, PMID:24469634). Downstream, EphB2 controls cytoskeletal collapse and contact repulsion through multiple effector arms: recruitment of p120RasGAP to downregulate Ras-Erk, a Pak/Nck/RhoA pathway for growth cone collapse, Rac/Tiam2-dependent and Eps15R/clathrin-mediated trans-endocytosis, and MMP-2/MMP-9 ectodomain cleavage required for repulsion (PMID:12486127, PMID:18713744, PMID:27597758, PMID:23147113, PMID:28972287). EphB2 is sequentially processed by ectodomain sheddases and presenilin/γ-secretase to release an intracellular CTF2 fragment that retains kinase activity and directly phosphorylates NMDA receptor subunits to promote their surface expression (PMID:17428795, PMID:19661068). In neurons EphB2 regulates NMDA receptor-mediated currents and synaptic plasticity through both kinase-dependent and kinase-independent (including PDZ-motif-mediated) mechanisms, and amyloid-β oligomers bind its fibronectin repeats to trigger proteasomal degradation, linking EphB2 to memory deficits (PMID:11754836, PMID:11754835, PMID:21113149, PMID:26589795). Beyond the nervous system, EphB2 partitions intestinal progenitor proliferation (Abl-cyclin D1) from migration (PI3K), drives cancer stemness and drug resistance via SRC/AKT/GSK3β/β-catenin and R-Ras/MAPK cascades, promotes liver fibrosis and NASH inflammation, and supports platelet GPVI/PAR signaling through its kinase domain, where a human p.R745C mutation impairing autophosphorylation causes a platelet function disorder (PMID:19914164, PMID:16049340, PMID:33903122, PMID:36753562, PMID:29416088, PMID:30213874).

Mechanistic history

Synthesis pass · year-by-year structured walk · 21 steps
  1. 1995 Low

    Establishing EPHB2 as an EPH-family receptor tyrosine kinase enriched in fetal brain and induced during neuronal differentiation framed it as a candidate regulator of neurogenesis.

    Evidence cDNA cloning, expression profiling, and chromosomal mapping in differentiating NTera-2 cells

    PMID:8589679

    Open questions at the time
    • Initial cloning lacks any mechanistic functional assay
    • No ligand or downstream pathway defined at this stage
  2. 1998 High

    Solving the ligand-binding domain structure and identifying Y611 as the SH2 docking site for Src defined how EphB2 recognizes ephrins and how its phosphorylated juxtamembrane region recruits effectors.

    Evidence X-ray crystallography of the ligand-binding domain plus Y2H, mutagenesis, Co-IP and phosphopeptide mapping for Src association

    PMID:9632142 PMID:9853759

    Open questions at the time
    • Did not resolve the autoinhibited conformation of the kinase domain
    • Full repertoire of SH2 effectors not yet enumerated
  3. 2000 Medium

    EphB2 knockout phenotypes in the inner ear revealed a role in efferent axon guidance and epithelial ion homeostasis through PDZ-mediated complexes with membrane channels, extending its function beyond axon repulsion.

    Evidence EphB2 knockout mouse phenotyping plus PDZ-binding assays

    PMID:10839360

    Open questions at the time
    • Direct channel partners within the macromolecular complex not biochemically confirmed in vivo
    • Forward versus reverse signaling contributions not separated here
  4. 2001 High

    Crystallography of the autoinhibited kinase domain and dissection of Abl/Arg binding established the structural switch underlying activation and the breadth of non-receptor kinase effectors, while knockout/knock-in mice showed EphB2 regulates NMDA receptor synaptic function partly independently of its kinase domain.

    Evidence 1.9 Å crystal structure with mutagenesis; Y2H and Co-IP for Abl/Arg; EphB2-null and truncated knock-in mice with electrophysiology and immunogold

    PMID:11494128 PMID:11572780 PMID:11754835 PMID:11754836

    Open questions at the time
    • Molecular basis of kinase-independent NMDA receptor regulation left undefined
    • How distinct Abl/Arg interaction modes are coordinated in vivo unresolved
  5. 2002 High

    Re-engineering juxtamembrane docking sites showed that RasGAP recruitment downregulates Ras-Erk to drive neurite retraction, providing a defined effector pathway linking EphB2 phosphorylation to cytoskeletal collapse.

    Evidence Receptor mutagenesis with phospho-Erk immunoblotting and neurite retraction assays in NG108 neurons

    PMID:12486127

    Open questions at the time
    • Relative contribution of RasGAP versus other repulsive arms not quantified
    • In vivo relevance of this pathway not tested
  6. 2004 High

    Demonstrating high-affinity cross-subclass binding of EphB2 to ephrin-A5 with a distinct complex architecture revised the rule that EphB and ephrin-A pairs do not interact, broadening EphB2's ligand repertoire and signaling outputs.

    Evidence Crystallography plus receptor clustering, autophosphorylation, and growth cone collapse assays

    PMID:15107857

    Open questions at the time
    • Physiological contexts where ephrin-A5/EphB2 signaling operates not established
    • Whether cross-subclass complexes assemble in vivo unaddressed
  7. 2005 Medium

    Identifying R-Ras as an EphB2-associated effector controlling glioma adhesion, proliferation, and invasion linked EphB2 to a tumor-relevant MAPK-suppressing axis.

    Evidence Co-IP, siRNA depletion, and adhesion/invasion/proliferation assays with MAPK readout

    PMID:16049340

    Open questions at the time
    • Single-lab Co-IP without reciprocal structural mapping
    • Direct versus indirect EphB2-R-Ras association not resolved
  8. 2007 High

    Mapping sequential ectodomain shedding and presenilin/γ-secretase cleavage that releases EphB2/CTF2 revealed regulated intramembrane proteolysis as a mechanism converting receptor activation into an intracellular signaling fragment.

    Evidence Pharmacological inhibitors, endocytosis blockade, biochemical cleavage mapping, and ubiquitination assays

    PMID:17428795

    Open questions at the time
    • Function of the released CTF2 fragment not yet demonstrated here
    • Identity of the initial ectodomain sheddase only partially defined
  9. 2008 Medium

    Showing MMP-2/MMP-9 ectodomain cleavage is required for repulsion, and that FGFR1 suppresses EphB2 via LAR phosphatase and Sprouty feedback, established proteolytic and cross-receptor control of EphB2 segregation activity.

    Evidence MMP inhibitors and cleavage-resistant mutants with rescue in EphB-deficient neurons; LAR knockdown, MAPK inhibitors, and Sprouty analysis in segregation assays

    PMID:18713744 PMID:19047466

    Open questions at the time
    • Quantitative integration of cleavage with clustering thresholds not addressed
    • FGFR1 cross-talk validated in cell-based assays only
  10. 2009 High

    Demonstrating that EphB2/CTF2 directly phosphorylates NR1/NR2 independently of Src, and that EphB2 segregates intestinal proliferation (Abl-cyclin D1) from migration (PI3K), defined parallel kinase-dependent and kinase-independent output modules whose uncoupling enables cancer.

    Evidence In vitro kinase assays with kinase-dead mutants and Src inhibitors; genetic dissection of intestinal progenitors with pathway inhibitors

    PMID:19661068 PMID:19914164

    Open questions at the time
    • Substrate selectivity of CTF2 beyond NMDA subunits not mapped
    • Mechanism dissociating proliferation and migration pathways in carcinoma unresolved
  11. 2010 High

    Identifying amyloid-β oligomer binding to EphB2 fibronectin repeats with consequent proteasomal degradation, and rescue of LTP/memory by EphB2 restoration, placed EphB2 mechanistically in Alzheimer's disease synaptic dysfunction.

    Evidence Biochemical Aβ binding, in vivo shRNA/overexpression, electrophysiology, and behavioral memory tests in hAPP mice

    PMID:21113149

    Open questions at the time
    • Degradation machinery downstream of Aβ binding not fully defined
    • Whether degradation acts on full-length receptor or processed fragments unclear
  12. 2011 High

    Neuropsin-mediated cleavage controlling EphB2-NR1 dissociation in the amygdala, and EphB2 kinase-dependent control of dentate progenitor migration, showed proteolytic and forward-signaling regulation of EphB2 in behavior and neurodevelopment.

    Evidence Neuropsin-KO mice with EphB2-NR1 Co-IP, NMDA currents, and anxiety assays; EphB2 kinase-dead/truncation alleles with BrdU/nestin and Reelin staining

    PMID:21508957 PMID:21832177

    Open questions at the time
    • Generality of neuropsin cleavage outside the amygdala not established
    • Reelin link to progenitor migration mechanistically indirect
  13. 2014 Medium

    Defining clustering-threshold-dependent repulsion, TF/FVIIa ectodomain cleavage potentiating repulsion, and EphB2-FAK coupling in glioblastoma refined the quantitative and proteolytic control of EphB2 signaling strength and migration.

    Evidence Chemical dimerizers and fluorescence anisotropy; Edman/LC-MS cleavage mapping; Co-IP and gain/loss-of-function with FAK phosphorylation

    PMID:22310282 PMID:24469634 PMID:25281742

    Open questions at the time
    • In vivo relevance of cluster-size thresholds not tested
    • TF/FVIIa cleavage characterized in single-lab cell assays
  14. 2016 Medium

    Identifying Rac/Tiam2-dependent F-actin enrichment driving trans-endocytosis and antidepressant-like mPFC effects of EphB2 activation linked specific GTPase machinery and synaptic remodeling to EphB2 forward signaling outcomes.

    Evidence siRNA Rho-GTPase screen, Tiam2 knockdown, and trans-endocytosis/repulsion assays; mPFC shRNA/EphrinB1-Fc with cofilin, AMPAR, and behavioral readouts

    PMID:27103064 PMID:27597758

    Open questions at the time
    • How Rac is locally activated at internalization sites unresolved
    • mPFC effects mechanistically correlative beyond cofilin/AMPAR changes
  15. 2017 Medium

    Demonstrating Eps15R/clathrin dependence of trans-endocytosis, Abl2/Arg-dependent dendritic filopodia growth, and an EphB2/Sirt3 antioxidant axis expanded the effector network connecting EphB2 to endocytic, cytoskeletal, and redox outcomes.

    Evidence siRNA and in vitro clathrin-binding rescue; optogenetic EphB2 with Arg knockdown and actin imaging; knockdown with Nrf-2/Src and MnSOD deacetylation assays

    PMID:28687409 PMID:28972287 PMID:29158322

    Open questions at the time
    • Each pathway validated in single labs and distinct cell systems
    • Integration of endocytic and actin-nucleating arms not unified
  16. 2018 High

    A human kinase-domain mutation (p.R745C) impairing autophosphorylation but not clustering established EphB2 as a positive regulator of platelet GPVI/PAR signaling and the basis of a human platelet function disorder, while optogenetic studies placed EphB2 forward signaling in fear memory consolidation and HSC-driven liver fibrosis.

    Evidence Whole-exome sequencing with patient platelets and heterologous expression; optogenetics with kinase-dead and lacZ-null mice and CREB readout; EphB2-KO mice with in vitro HSC activation

    PMID:29416088 PMID:29768201 PMID:30213874

    Open questions at the time
    • Direct platelet substrates of EphB2 not defined
    • Whether HSC fibrosis effect is cell-autonomous unresolved
  17. 2019 Medium

    Showing exosome-delivered EphB2 stimulates ephrin-B reverse signaling and STAT3 phosphorylation in endothelial cells revealed a non-cell-autonomous, vesicle-mediated route for EphB2 to drive tumor angiogenesis.

    Evidence SEV proteomics, EphB2 knockdown in SEVs, angiogenesis assays, and STAT3 inhibitor treatment

    PMID:31661464

    Open questions at the time
    • Mechanism of EphB2 loading into exosomes not defined
    • Direct endothelial receptor mediating reverse signaling not identified
  18. 2020 Medium

    Identifying RNF186-mediated ubiquitination of EphB2 at K892 triggering LC3B-dependent autophagy in colonic epithelium connected EphB2 to a post-translational autophagy switch protective against colitis.

    Evidence Co-IP, K892R ubiquitination mutant, LC3B autophagy markers, and rnf186/ephb2 KO mice in DSS colitis

    PMID:33280498

    Open questions at the time
    • How ubiquitinated EphB2 recruits the autophagy machinery mechanistically unresolved
    • Single-lab finding without reciprocal validation
  19. 2021 Medium

    Defining a TCF1-EphB2-SRC/AKT/GSK3β/β-catenin positive feedback loop driving liver cancer stemness and sorafenib resistance, and an EphB2-DGAT1/ATGL lipid-homeostasis link in prostate cancer, established opposing context-dependent roles of EphB2 in malignancy.

    Evidence EPHB2 KO and rAAV-shRNA with RNA-seq and xenograft models; siRNA knockdown with DGAT1 inhibitor and lipid droplet quantification

    PMID:33824421 PMID:33903122

    Open questions at the time
    • Reconciliation of tumor-promoting versus tumor-suppressive roles across cancers unresolved
    • Direct kinase substrates within these cascades not identified
  20. 2023 Medium

    Placing EphB2 as a Notch-downstream effector marking a profibrotic/inflammatory hepatocyte subpopulation showed it is sufficient to drive cell-autonomous inflammation in NASH progression.

    Evidence Single-nucleus multi-omics and hepatocyte-specific Ephb2 knockdown in a mouse NASH model with human data

    PMID:36753562

    Open questions at the time
    • Downstream inflammatory effectors of hepatocyte EphB2 not fully defined
    • Ligand driving hepatocyte EphB2 activation unidentified
  21. 2024 Medium

    Demonstrating ephrin-B2/EphB2 signaling through MNK-eIF4E to induce nociceptor plasticity and hyperalgesic priming in mouse and human DRG neurons defined a translational-control mechanism for EphB2 in pain.

    Evidence Sensory-neuron-specific EphB2 KO, MNK1 KO, MNK inhibitor, Ca2+ imaging, and behavioral pain assays in two species

    PMID:38925462

    Open questions at the time
    • How EphB2 forward signaling couples to MNK-eIF4E not biochemically mapped
    • Whether receptor proteolysis participates in this pathway untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • How EphB2's multiple effector arms, proteolytic processing events, and context-specific oncogenic versus tumor-suppressive outputs are coordinated at the level of a single activated receptor remains unresolved.
  • No unified model linking clustering state to choice of effector pathway
  • Determinants of opposing roles across tumor types not established
  • Comprehensive substrate map of full-length EphB2 and CTF2 lacking

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 5 GO:0060089 molecular transducer activity 3 GO:0060090 molecular adaptor activity 3 GO:0001618 virus receptor activity 2
Localization
GO:0005886 plasma membrane 3 GO:0031410 cytoplasmic vesicle 3
Pathway
R-HSA-112316 Neuronal System 5 R-HSA-1266738 Developmental Biology 4 R-HSA-162582 Signal Transduction 4 R-HSA-1643685 Disease 4 R-HSA-392499 Metabolism of proteins 4
Partners
ABL1EFNA5EFNB1EFNB2PAK1PTK2RASA1SRC

Evidence

Reading pass · 41 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 Crystal structure of the autoinhibited, unphosphorylated EphB2 kinase domain (with juxtamembrane region) at 1.9 Å resolution reveals that the juxtamembrane segment adopts a helical conformation that distorts the small lobe of the kinase domain and blocks the activation segment, providing structural autoinhibition. Phosphorylation of conserved juxtamembrane tyrosines relieves this autoinhibition by disrupting the JM-kinase interface and liberating phosphotyrosine sites for SH2-domain binding. X-ray crystallography + site-directed mutagenesis Cell High 11572780
1998 Crystal structure of the EphB2 ligand-binding domain at 2.9 Å resolution reveals a jellyroll beta-sandwich of 11 antiparallel beta-strands. Structure-based mutagenesis identified an extended loop critical for ligand binding and subclass specificity, localizing the ligand-binding surface to the concave beta-sandwich near positions where missense mutations cause signaling defects. X-ray crystallography + structure-based mutagenesis Nature High 9853759
2004 EphB2 and ephrin-A5 (a cross-subclass pair) bind each other with high affinity, triggering receptor clustering, autophosphorylation, and downstream signaling. Ephrin-A5 induces EphB2-mediated growth cone collapse and neurite retraction. Crystal structure reveals a heterodimeric complex architecturally distinct from the tetrameric EphB2-ephrinB2 structure, providing a molecular basis for cross-subclass signaling. X-ray crystallography, cell-based signaling assays (receptor clustering, autophosphorylation), growth cone collapse assay Nature neuroscience High 15107857
1998 Phosphorylated tyrosine 611 in the juxtamembrane region of EphB2 is a major autophosphorylation site and is required for interaction with the SH2 domain of Src kinase. Tyrosines 605 and 611 are important for EphB2 kinase activity. EphB2 and Src physically associate (co-immunoprecipitation), and activated EphB2 induces increased tyrosine phosphorylation of Src. Yeast two-hybrid, site-directed mutagenesis, co-immunoprecipitation, phosphopeptide mapping Oncogene High 9632142
2001 Abl and Arg non-receptor tyrosine kinases associate with EphB2 through multiple distinct interactions: (1) their SH2 domains bind phosphorylated juxtamembrane tyrosines of EphB2; (2) a phosphorylation-independent interaction involves C-terminal sequences of Abl/Arg; (3) a third interaction requires EphB2 phosphorylation but not direct SH2 binding. Activated EphB2 phosphorylates Abl and Arg, and ephrin-B1 stimulation decreases endogenous Abl kinase activity. Yeast two-hybrid, co-immunoprecipitation, kinase activity assay, ephrin-B1 stimulation of endogenous EphB2 Oncogene High 11494128
2001 EphB2 null mice exhibit reduced NMDA receptor-mediated synaptic current and reduced synaptically localized NR1 subunit (immunogold) in dentate granule neurons. Mice lacking only the intracellular kinase domain retain wild-type LTP, indicating that kinase-independent EphB2 functions mediate certain synaptic roles, whereas the extracellular/transmembrane domain is required for NMDA receptor regulation. EphB2 knockout mouse, electrophysiology (LTP, NMDA currents), immunogold localization Neuron High 11754836
2001 EphB2 kinase signaling is not required for protein synthesis-dependent LTP or for two forms of synaptic depression in hippocampal slices; a C-terminally truncated EphB2 (lacking kinase domain) rescues the EphB2 null phenotype, demonstrating kinase-independent regulation of synaptic plasticity. Eph receptor stimulation in cultured neurons modulates signaling pathways implicated in synaptic plasticity, suggesting cross-talk with NMDA receptor-activated pathways. EphB2 knockout mouse, targeted knock-in of truncated EphB2, LTP/LTD electrophysiology in hippocampal slices Neuron High 11754835
2010 Amyloid-β oligomers bind to the fibronectin repeats domain of EphB2 and trigger EphB2 degradation via the proteasome. EphB2 knockdown by shRNA reduces NMDA receptor currents and impairs LTP in dentate gyrus; increasing EphB2 expression in dentate gyrus of hAPP transgenic mice reverses NMDA receptor-dependent LTP deficits and memory impairments. Biochemical binding assay (Aβ oligomers + EphB2), lentiviral shRNA knockdown and overexpression in vivo, electrophysiology, behavioral memory tests Nature High 21113149
2011 The serine protease neuropsin cleaves EphB2 in the amygdala upon stress, causing dissociation of EphB2 from the NR1 subunit of the NMDA receptor and promoting membrane turnover of EphB2 receptors. Dynamic EphB2-NR1 interaction enhances NMDA receptor current, induces Fkbp5 gene expression, and increases anxiety-like behaviour. Neuropsin-deficient mice lack EphB2 cleavage and show attenuated anxiety. Neuropsin knockout mice, intra-amygdala injection of neuropsin/antibodies/shRNA, EphB2-NR1 co-immunoprecipitation, NMDA receptor current recordings, behavioural assays Nature High 21508957
2007 EphB2 receptor ectodomain is cleaved after residue 543; the remaining membrane fragment is then cleaved by presenilin-dependent γ-secretase after residue 569, releasing an intracellular peptide (EphB2/CTF2). Ephrin-B ligand-induced processing requires endocytosis and is sensitive to proteasomal (not metalloproteinase) inhibitors. Calcium influx/NMDA-induced processing is sensitive to GM6001 and ADAM10 inhibitors and occurs at the plasma membrane without endocytosis. Ligand stimulation also induces ubiquitination of EphB2. Pharmacological inhibitors, endocytosis blockade, biochemical cleavage mapping, ubiquitination assay The Journal of biological chemistry High 17428795
2009 The γ-secretase-derived intracellular peptide EphB2/CTF2 retains tyrosine kinase activity and directly phosphorylates NMDA receptor subunits (NR1, NR2) in cell lines and primary neuronal cultures, independently of Src kinases. A kinase-dead EphB2/CTF2 mutant lacks this activity. EphB2/CTF2 promotes cell-surface expression of NMDA receptors. In vitro kinase assay, Src inhibitors, kinase-dead mutant, cell-surface expression assay (primary neurons and cell lines) The Journal of biological chemistry High 19661068
2002 EphB2 recruits p120RasGAP via juxtamembrane (JM) binding sites, leading to down-regulation of the Ras-Erk MAPK pathway and neurite retraction. Elimination of RasGAP binding sites with addition of Grb2 binding sites within the kinase domain activates Erk MAPK upon ephrin-B1 stimulation. This confirms that EphB2-mediated neurite retraction correlates with Ras-Erk MAPK down-regulation mediated through RasGAP recruitment. Receptor mutagenesis/re-engineering, phospho-Erk immunoblotting, neurite retraction functional assay in NG108 neurons The Journal of biological chemistry High 12486127
2008 MMP-2 and MMP-9 cleave EphB2 in its ectodomain upon ephrin-B2 binding in vitro and in vivo. MMP-specific inhibition or cleavage-resistant EphB2 ectodomain mutations prevent EphB2-mediated cell-cell repulsion in HEK293 cells and block ephrin-B1-induced growth cone withdrawal in hippocampal neurons. Expression of cleavable but not non-cleavable EphB2 rescues ephrin-B1-induced growth cone collapse in EphB-deficient neurons. MMP inhibitors, cleavage-resistant mutagenesis, cell repulsion assay, growth cone collapse assay in EphB-deficient neurons, in vitro and in vivo cleavage assays The Journal of biological chemistry High 18713744
2009 EphB2 regulates intestinal progenitor cell migration and proliferation through two independent signaling pathways: kinase-independent, PI3K-mediated control of cell positioning/migration; and tyrosine kinase-dependent regulation of proliferation through an Abl-cyclin D1 pathway. These pathways dissociate during colon carcinoma progression, allowing continued proliferation with invasive growth. Genetic dissection with EphB2 mutants (kinase-dead, truncated), PI3K inhibitors, Abl inhibitors, cyclin D1 measurement, intestinal cell positioning assays Cell High 19914164
2005 Upon EphB2 activation, R-Ras associates with EphB2 receptor and becomes highly phosphorylated. siRNA depletion of R-Ras abrogates EphB2 effects on glioma cell adhesion, proliferation, and invasion. Anti-proliferative responses correlate with suppressed MAPK activity, identifying EphB2/R-Ras as a functionally relevant signaling axis. Co-immunoprecipitation, siRNA knockdown, invasion/adhesion/proliferation assays, MAPK activity assay The American journal of pathology Medium 16049340
2008 FGFR1 activation prevents EphB2-mediated cell segregation and repulsion by: (1) increasing basal EphB2 phosphorylation through down-regulation of the leukocyte common antigen-related (LAR) tyrosine phosphatase that dephosphorylates EphB2; and (2) inhibiting further EphB2 phosphorylation upon ephrinB1 stimulation via MAPK pathway-induced Sprouty genes. EphB2 normally activates the MAPK pathway, which feeds back positively to promote EphB2 activation. Phosphorylation analysis, LAR phosphatase knockdown, MAPK inhibitors, Sprouty expression, cell segregation/repulsion assays The Journal of cell biology Medium 19047466
2014 EphB2 clustering determines repulsive signaling strength: small clusters (trimers/tetramers) are sufficient to induce cell collapse, with dimers being inactive. Extended EphB2 arrays are dispensable. The ratio of multimers to dimers within a cluster population determines collapse response strength. The C-terminal modules of EphB2 have negative regulatory effects on ephrin-induced clustering. Chemical dimerizers, fluorescence anisotropy in live cells, quantitative imaging, collapse response assays The Journal of cell biology Medium 24469634
2016 Rac-dependent F-actin enrichment at sites of EphB2 internalization (not during vesicle trafficking) mediates trans-endocytosis. Systematic Rho GTPase depletion identified Rac subfamily and Tiam2 (Rac-specific GEF) as key components of EphB2 trans-endocytosis from opposing ephrinB+ cells, and this pathway is required for EphB2-stimulated contact repulsion. Live imaging, systematic siRNA screen of Rho GTPases, Tiam2 knockdown, trans-endocytosis assay, cell repulsion assay The Journal of cell biology Medium 27597758
2012 EphB2 forward signaling mediates cortical growth cone collapse via Pak and Nck: kinase-active EphB2 binds Pak, promotes growth cone repulsion via Pak kinase activity, Pak-Nck binding, RhoA signaling and endocytosis. This occurs independently of Rac/Cdc42-GTP production after ephrinB treatment of cortical neurons. Co-immunoprecipitation (EphB2-Pak), dominant-negative constructs, endocytosis blockade, growth cone collapse assay in cortical neurons Molecular and cellular neurosciences Medium 23147113
2017 Optogenetic (OptoEphB2) photoactivation of EphB2 in dendrites of hippocampal neurons induces rapid actin polymerization and dynamic dendritic filopodial growth. Rac1 and Cdc42 inhibition does not abolish this effect; instead, Abl2/Arg kinase is required as a necessary effector for OptoEphB2-induced filopodia growth in dendrites. Optogenetic EphB2 activation, Rac1/Cdc42 inhibitors, Arg kinase knockdown/inhibition, live-cell actin imaging Biology open Medium 29158322
2015 EphB2 activation (by ephrinB1/Fc or overexpression plus ligand) induces tau dephosphorylation at multiple AD-associated sites through PI3K/Akt-mediated inhibition of GSK-3β. PI3K inhibition or GSK-3β upregulation abolishes this effect. Deletion of the tyrosine kinase domain eliminates EphB2 stimulation-induced GSK-3β inhibition and tau dephosphorylation, demonstrating kinase-dependence. Kinase-dead mutant, PI3K inhibitors, GSK-3β overexpression, phospho-tau immunoblotting in cell lines, primary neurons, and transgenic mice Scientific reports Medium 26119563
2015 The protective effect of EphB2 against Aβ-induced depletion of surface NMDA receptors depends on EphB2's PDZ-binding motif and the presence of neuronal activity, but not on its kinase activity. The GluA2 subunit of AMPA receptors associates with EphB2's PDZ-binding motif via PDZ domain-containing proteins and promotes NMDA receptor retention at the membrane. Pharmacological treatments, primary neuronal cultures expressing wild-type or PDZ-motif/kinase-dead EphB2 mutants, biochemical co-association assays The Journal of biological chemistry Medium 26589795
2018 Photoactivation of OptoEphB2 (kinase-active) during fear conditioning (but not minutes afterward) enhances long-term fear memory consolidation and activates CREB in lateral amygdala neurons. Kinase-dead OptoEphB2 lacks these effects. EphB2lacZ/lacZ mice lacking forward signaling show impaired long-term auditory fear conditioning memory, rescued by optoEphB2 activation. Optogenetics, kinase-dead mutant, EphB2lacZ/lacZ knockout mice, CREB phosphorylation, behavioral fear conditioning Cell reports Medium 29768201
2011 EphB2 tyrosine kinase forward signaling (catalytic activity is essential) controls migration of nestin-positive neural progenitor cells from the dentate notch neuroepithelium to populate the lateral suprapyramidal blade (LSB) of the dentate gyrus. Ephrin-B1 acts as the ligand for EphB2 in this context. Loss of EphB2 forward signaling dramatically reduces Reelin immunoreactivity in a compartment above the developing LSB. EphB2 kinase-dead and truncation mutants in mice, BrdU/nestin labeling, Reelin immunostaining, ephrin-B1 knockout comparison The Journal of neuroscience Medium 21832177
2000 EphB2 is expressed in K+-secreting dark cells of the inner ear epithelium and is required for proper efferent axon midline guidance and for endolymph homeostasis. PDZ domain-containing proteins bind the C-terminus of EphB2 and can also recognize cytoplasmic tails of anion exchangers and aquaporins, suggesting EphB2 regulates ionic homeostasis through macromolecular complexes with membrane channels. EphB2 knockout mouse (circling behavior, vestibular phenotype analysis), PDZ binding assay, ultrastructural analysis Neuron Medium 10839360
2006 Bidirectional signaling by EphB2 (forward) and ephrin-B2 (reverse) is required for proper K+ secretion and ionic homeostasis in vestibular endolymph. Mutations disrupting EphB2 forward signaling or ephrin-B2 reverse signaling decrease K+ concentration and endolymphatic potential, demonstrating that B-subclass Eph/ephrin signaling controls epithelial ion transport function. Targeted mutations (cytoplasmic domain) of EphB2 and ephrin-B2 in mice, direct electrophysiological measurement of endolymphatic potential and K+ concentration in live animals Hearing research Medium 17158005
2019 EPHB2 carried on small extracellular vesicles (exosomes) induces tumor angiogenesis by transporting the transmembrane receptor to non-adjacent endothelial cells, stimulating ephrin-B reverse signaling and STAT3 phosphorylation. A STAT3 inhibitor greatly reduces SEV-induced angiogenesis. Proteomic analysis of SEVs, EPHB2 knockdown in SEVs, in vitro and in vivo angiogenesis assays, STAT3 phosphorylation analysis, STAT3 inhibitor treatment JCI insight Medium 31661464
2020 RNF186, an E3 ubiquitin ligase, ubiquitinates EPHB2 at Lys892 upon stimulation by ligand EFNB1. Ubiquitinated EPHB2 recruits MAP1LC3B to activate autophagy in colonic epithelial cells. rnf186 and ephb2 knockout mice show more severe DSS-induced colitis due to autophagy defects in colon epithelial cells. Co-immunoprecipitation, ubiquitination assay (K892R mutant), autophagy markers (LC3B), KO mice + DSS colitis model Autophagy Medium 33280498
2021 EPHB2 drives liver cancer stemness and sorafenib resistance through activation of the SRC/AKT/GSK3β/β-catenin signaling cascade. EPHB2 expression is regulated by TCF1 via promoter activation, forming a positive Wnt/β-catenin feedback loop. EPHB2 knockout attenuates tumor development and rAAV-8-shEPHB2 sensitizes HCC cells to sorafenib. EPHB2 knockout (endogenous), RNA-seq, signaling pathway analysis, xenograft and immunocompetent mouse models, rAAV-mediated shRNA knockdown Cancer research Medium 33903122
2023 EphB2, acting as a downstream effector of Notch signaling in hepatocytes, is sufficient to induce cell-autonomous inflammation during NASH progression. Knockdown of Ephb2 in hepatocytes ameliorates inflammation and fibrosis in a mouse NASH model. EphB2-expressing hepatocytes are specifically demarcated as a profibrotic/inflammatory subpopulation. Single-nucleus transcriptomics/epigenomics, Notch pathway analysis, hepatocyte-specific Ephb2 knockdown in NASH mouse model, inflammation/fibrosis readouts Science translational medicine Medium 36753562
2018 EphB2 is upregulated and activated in hepatic stellate cells (HSCs) during fibrogenesis. EphB2-deficient HSCs show impaired proliferation and suboptimal differentiation into fibrogenic myofibroblasts in vitro, identifying HSC activation as a cellular mechanism through which EphB2 promotes liver fibrosis. EphB2 knockout mice, in vitro HSC activation, fibrosis markers, apoptosis assays Scientific reports Medium 29416088
2014 Tissue factor (TF)/coagulation factor VIIa (FVIIa) cleaves EphB2 ectodomain at a key arginine residue (identified by Edman sequencing and LC-MS/MS). This cleavage is independent of PAR2 signaling and potentiates cell repulsion mediated by the EphB2 ligand ephrin-B1, identifying TF/FVIIa as a novel protease controlling Eph-mediated cell segregation. N-terminal Edman sequencing, LC-MS/MS, PAR2 inhibition, cell repulsion assay The Journal of biological chemistry Medium 25281742
2018 A human missense mutation p.R745C in the EphB2 kinase domain impairs EphB2 autophosphorylation but not ephrin ligand-induced EphB2 clustering. This results in defects in platelet aggregation, αIIbβ3 activation, granule secretion, and thrombus formation. EPHB2 positively regulates GPVI platelet signaling (Lyn, Syk, FcRγ phosphorylation) and Src activation downstream of PAR4. Whole-exome sequencing, patient platelets, overexpression in RBL-2H3 cells, platelet aggregation/flow assays, phosphorylation analysis Blood High 30213874
2014 EphB2 co-associates with and activates focal adhesion kinase (FAK) in glioblastoma neurosphere cells, facilitating focal adhesion formation, cytoskeletal changes, and cell migration. EphB2 expression stimulates invasion and inhibits proliferation in vitro and in vivo. Co-immunoprecipitation (EphB2-FAK), EphB2 overexpression/silencing, FAK phosphorylation analysis, migration/invasion/proliferation assays, xenograft model Oncogene Medium 22310282
2017 EphB2 signaling induces mitochondrial translocation of Sirt3. EphrinB2-Fc induces nuclear translocation of Nrf-2 via c-Src phosphorylation, and Sirt3 expression is regulated by Nrf-2. EphB2/Sirt3 signaling increases MnSOD activity (by deacetylation at Lys68) to reduce mitochondrial ROS and suppress MSC senescence. EphB2 knockdown, Sirt3 knockdown, subcellular fractionation, Nrf-2/Src phosphorylation analysis, MnSOD deacetylation/activity assay, ROS measurement Free radical biology & medicine Medium 28687409
2024 Ephrin-B2 acts on mouse and human DRG neurons via EphB2 to induce nociceptor plasticity and hyperalgesic priming through MNK-eIF4E signaling. Sensory neuron-specific EphB2 knockout (Pirt-Cre) abrogates ephrin-B2-induced mechanical hypersensitivity and enhanced Ca2+ responses to PGE2. MNK1 knockout or MNK inhibitor (eFT508) blocks acute and priming responses. Conditional EphB2 knockout (Pirt-Cre), MNK1 knockout, MNK inhibitor, Ca2+ imaging in cultured DRG neurons (mouse and human), behavioral pain assays Pharmacological research Medium 38925462
2017 EphB2 receptor repulsion trans-endocytosis requires Eps15R and clathrin. Eps15R (but not Eps15) knockdown significantly reduces EphB2-mediated cell repulsion. A novel DPFxxLDPF motif in Eps15R binds directly to the clathrin terminal domain in vitro; wild-type Eps15R but not the clathrin-binding mutant rescues cell repulsion. siRNA knockdown, in vitro clathrin-binding assay, rescue experiments in co-culture cell repulsion assay Traffic Medium 28972287
2016 EphB2 activation in the medial prefrontal cortex (mPFC) via EphrinB1-Fc produces stress-resistant and antidepressant-like effects. EphB2 shRNA knockdown in the mPFC increases stress susceptibility. These effects are associated with changes in cofilin phosphorylation, membrane AMPA receptor trafficking, and spine remodeling. Lentiviral shRNA knockdown, EphrinB1-Fc intra-mPFC injection, behavioral assays, cofilin phosphorylation, AMPAR surface trafficking, spine analysis Neuropsychopharmacology Medium 27103064
2021 Loss of EPHB2 in prostate cancer cells increases lipogenic DGAT1, DGAT2, and PLIN2 and decreases lipolytic ATGL and PEDF, leading to lipid droplet accumulation in cytoplasmic and nuclear compartments. A DGAT1-specific inhibitor abrogates LD accumulation and proliferative effects induced by EPHB2 loss, mechanistically linking EPHB2 to lipid homeostasis via DGAT1/ATGL regulation. EPHB2 siRNA knockdown, DGAT1 inhibitor, lipid droplet quantification, proliferation assays, protein expression analysis Laboratory investigation Medium 33824421
1995 DRT (EPHB2/EPHT3) encodes a receptor-type tyrosine kinase of the EPH family. Its 11 kb transcript is preferentially expressed in fetal brain and is upregulated upon retinoic acid-induced neuronal differentiation of NTera-2 cells, indicating a role in neurogenesis. The gene was mapped to human chromosome 1p35-1p36.1. cDNA library screening with anti-phosphotyrosine antibody, 5' RACE, RT-PCR, chromosomal mapping by somatic cell hybrid panels and FISH, retinoic acid differentiation assay Human molecular genetics Low 8589679
2014 EphB2 signaling in B cells promotes proliferation, TNF-α secretion, and IgG production in human naive B cells. EphB2 knockdown attenuates B-cell activation via reduction of Src-p65 (NF-κB) and Notch1 signaling pathways. EphB2 siRNA in human primary B cells, proliferation assay, ELISA (cytokines/Ig), Src/p65/Notch1 pathway analysis FASEB journal Low 24803541

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2004 Repelling class discrimination: ephrin-A5 binds to and activates EphB2 receptor signaling. Nature neuroscience 378 15107857
2010 Reversing EphB2 depletion rescues cognitive functions in Alzheimer model. Nature 350 21113149
2001 Structural basis for autoinhibition of the Ephb2 receptor tyrosine kinase by the unphosphorylated juxtamembrane region. Cell 279 11572780
2001 The receptor tyrosine kinase EphB2 regulates NMDA-dependent synaptic function. Neuron 267 11754836
2001 Kinase-independent requirement of EphB2 receptors in hippocampal synaptic plasticity. Neuron 250 11754835
2004 Bidirectional signaling mediated by ephrin-B2 and EphB2 controls urorectal development. Developmental biology 197 15223334
2000 EphB2 guides axons at the midline and is necessary for normal vestibular function. Neuron 178 10839360
2011 Neuropsin cleaves EphB2 in the amygdala to control anxiety. Nature 166 21508957
2004 The phosphorylation of EphB2 receptor regulates migration and invasion of human glioma cells. Cancer research 148 15126357
2009 Dissociation of EphB2 signaling pathways mediating progenitor cell proliferation and tumor suppression. Cell 145 19914164
2005 EphB2/R-Ras signaling regulates glioma cell adhesion, growth, and invasion. The American journal of pathology 128 16049340
2009 Preferential induction of EphB4 over EphB2 and its implication in colorectal cancer progression. Cancer research 120 19366806
2021 EPHB2 Activates β-Catenin to Enhance Cancer Stem Cell Properties and Drive Sorafenib Resistance in Hepatocellular Carcinoma. Cancer research 118 33903122
2019 EPHB2 carried on small extracellular vesicles induces tumor angiogenesis via activation of ephrin reverse signaling. JCI insight 111 31661464
2005 Reduced expression of EphB2 that parallels invasion and metastasis in colorectal tumours. Carcinogenesis 107 16272170
2007 Ligand binding and calcium influx induce distinct ectodomain/gamma-secretase-processing pathways of EphB2 receptor. The Journal of biological chemistry 105 17428795
2004 Expression of Ephb2 and Ephb4 in breast carcinoma. Pathology oncology research : POR 104 15029258
1998 Complex formation between EphB2 and Src requires phosphorylation of tyrosine 611 in the EphB2 juxtamembrane region. Oncogene 101 9632142
1998 Crystal structure of the ligand-binding domain of the receptor tyrosine kinase EphB2. Nature 93 9853759
2005 EphB2 expression across 138 human tumor types in a tissue microarray: high levels of expression in gastrointestinal cancers. Clinical cancer research : an official journal of the American Association for Cancer Research 88 16166419
2008 Ephrin-B2-induced cleavage of EphB2 receptor is mediated by matrix metalloproteinases to trigger cell repulsion. The Journal of biological chemistry 87 18713744
2012 EphB2 receptor controls proliferation/migration dichotomy of glioblastoma by interacting with focal adhesion kinase. Oncogene 80 22310282
2005 Mechanisms of inactivation of the receptor tyrosine kinase EPHB2 in colorectal tumors. Cancer research 79 16288001
2006 EphB2 and EphB4 receptors forward signaling promotes SDF-1-induced endothelial cell chemotaxis and branching remodeling. Blood 78 16840724
2008 Regulation of EphB2 activation and cell repulsion by feedback control of the MAPK pathway. The Journal of cell biology 75 19047466
2014 The composition of EphB2 clusters determines the strength in the cellular repulsion response. The Journal of cell biology 74 24469634
2001 Multiple signaling interactions of Abl and Arg kinases with the EphB2 receptor. Oncogene 70 11494128
2011 Identifying transient protein-protein interactions in EphB2 signaling by blue native PAGE and mass spectrometry. Proteomics 69 21932443
2002 Manipulation of EphB2 regulatory motifs and SH2 binding sites switches MAPK signaling and biological activity. The Journal of biological chemistry 65 12486127
2013 TNF-α/NF-κB signaling in the CNS: possible connection to EPHB2. Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology 61 24277482
2008 Overexpression of EphA4 gene and reduced expression of EphB2 gene correlates with liver metastasis in colorectal cancer. International journal of oncology 58 18695888
2023 Hepatocytes demarcated by EphB2 contribute to the progression of nonalcoholic steatohepatitis. Science translational medicine 56 36753562
2007 Cupredoxin-cancer interrelationship: azurin binding with EphB2, interference in EphB2 tyrosine phosphorylation, and inhibition of cancer growth. Biochemistry 56 17249693
2015 EphB2 Promotes Progression of Cutaneous Squamous Cell Carcinoma. The Journal of investigative dermatology 54 25789706
2020 RNF186 regulates EFNB1 (ephrin B1)-EPHB2-induced autophagy in the colonic epithelial cells for the maintenance of intestinal homeostasis. Autophagy 52 33280498
2015 Stimulation of EphB2 attenuates tau phosphorylation through PI3K/Akt-mediated inactivation of glycogen synthase kinase-3β. Scientific reports 52 26119563
2016 miR-204 downregulates EphB2 in aging mouse hippocampal neurons. Aging cell 51 26799631
2013 EphB2 promotes cervical cancer progression by inducing epithelial-mesenchymal transition. Human pathology 50 24439224
2008 EphB2 and EphB3 forward signalling are required for palate development. Mechanisms of development 47 19032981
2013 Role of the EphB2 receptor in autophagy, apoptosis and invasion in human breast cancer cells. Experimental cell research 45 24211352
2012 EphB2 activity plays a pivotal role in pediatric medulloblastoma cell adhesion and invasion. Neuro-oncology 42 22723427
2015 The receptor tyrosine kinase EphB2 promotes hepatic fibrosis in mice. Hepatology (Baltimore, Md.) 41 25784101
2023 Fusobacterium nucleatum-induced exosomal HOTTIP promotes gastric cancer progression through the microRNA-885-3p/EphB2 axis. Cancer science 39 36898846
2018 EphB2 receptor tyrosine kinase promotes hepatic fibrogenesis in mice via activation of hepatic stellate cells. Scientific reports 38 29416088
2022 The Roles of EphB2 in Cancer. Frontiers in cell and developmental biology 37 35223830
2006 EphB2 and ephrin-B2 regulate the ionic homeostasis of vestibular endolymph. Hearing research 37 17158005
2019 EphB2-dependent signaling promotes neuronal excitotoxicity and inflammation in the acute phase of ischemic stroke. Acta neuropathologica communications 36 30722785
2016 EphB2 in the Medial Prefrontal Cortex Regulates Vulnerability to Stress. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 36 27103064
2006 High EPHB2 mutation rate in gastric but not endometrial tumors with microsatellite instability. Oncogene 36 16819508
2005 Altered expression patterns of EphrinB2 and EphB2 in human umbilical vessels and congenital venous malformations. Pediatric research 35 15718372
2010 EphB2-mediated interactions are essential for proper migration of T cell progenitors during fetal thymus colonization. Journal of leukocyte biology 34 20504947
2018 EphB2 stem-related and EphA2 progression-related miRNA-based networks in progressive stages of CRC evolution: clinical significance and potential miRNA drivers. Molecular cancer 33 30501625
2016 Tiam-Rac signaling mediates trans-endocytosis of ephrin receptor EphB2 and is important for cell repulsion. The Journal of cell biology 33 27597758
2017 miR-204 Regulates Cell Proliferation and Invasion by Targeting EphB2 in Human Cervical Cancer. Oncology research 32 28800788
2021 circMELK promotes glioblastoma multiforme cell tumorigenesis through the miR-593/EphB2 axis. Molecular therapy. Nucleic acids 31 34168916
2014 Increased EphB2 expression predicts cholangiocarcinoma metastasis. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 31 25012246
2009 Peptide EphB2/CTF2 generated by the gamma-secretase processing of EphB2 receptor promotes tyrosine phosphorylation and cell surface localization of N-methyl-D-aspartate receptors. The Journal of biological chemistry 31 19661068
2015 Increasing the Receptor Tyrosine Kinase EphB2 Prevents Amyloid-β-induced Depletion of Cell Surface Glutamate Receptors by a Mechanism That Requires the PDZ-binding Motif of EphB2 and Neuronal Activity. The Journal of biological chemistry 30 26589795
2018 Activation of EphB2 Forward Signaling Enhances Memory Consolidation. Cell reports 29 29768201
2011 EphB2 tyrosine kinase-dependent forward signaling in migration of neuronal progenitors that populate and form a distinct region of the dentate niche. The Journal of neuroscience : the official journal of the Society for Neuroscience 29 21832177
2019 EphrinB2/ephB2-mediated myenteric synaptic plasticity: mechanisms underlying the persistent muscle hypercontractility and pain in postinfectious IBS. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 28 31601124
2017 EphB2 signaling-mediated Sirt3 expression reduces MSC senescence by maintaining mitochondrial ROS homeostasis. Free radical biology & medicine 28 28687409
1995 Molecular characterization and chromosomal localization of DRT (EPHT3): a developmentally regulated human protein-tyrosine kinase gene of the EPH family. Human molecular genetics 28 8589679
2018 EphB2 Deficiency Induces Depression-Like Behaviors and Memory Impairment: Involvement of NMDA 2B Receptor Dependent Signaling. Frontiers in pharmacology 27 30131699
2012 EphB2 receptor forward signaling controls cortical growth cone collapse via Nck and Pak. Molecular and cellular neurosciences 27 23147113
2021 Key role for EphB2 receptor in kidney fibrosis. Clinical science (London, England : 1979) 26 34462781
2016 Proper closure of the optic fissure requires ephrin A5-EphB2-JNK signaling. Development (Cambridge, England) 26 26839344
2021 Loss of ephrin B2 receptor (EPHB2) sets lipid rheostat by regulating proteins DGAT1 and ATGL inducing lipid droplet storage in prostate cancer cells. Laboratory investigation; a journal of technical methods and pathology 25 33824421
2017 Nanopatterns of Surface-Bound EphrinB1 Produce Multivalent Ligand-Receptor Interactions That Tune EphB2 Receptor Clustering. Nano letters 25 29243484
2016 EPH/ephrin profile and EPHB2 expression predicts patient survival in breast cancer. Oncotarget 25 26870995
2008 Expression and function of ephrin-B1 and its cognate receptor EphB2 in human atherosclerosis: from an aspect of chemotaxis. Clinical science (London, England : 1979) 25 18092944
2016 Bradykinin receptors and EphB2/EphrinB2 pathway in response to high glucose-induced osteoblast dysfunction and hyperglycemia-induced bone deterioration in mice. International journal of molecular medicine 24 26782642
2014 The differential expression of EphB2 and EphB4 receptor kinases in normal bladder and in transitional cell carcinoma of the bladder. PloS one 24 25148033
2001 Association among EPHB2, TrkA, and MYCN expression in low-stage neuroblastomas. Medical and pediatric oncology 24 11464911
2019 Qingyihuaji formula reverses gemcitabine resistant human pancreatic cancer through regulate lncRNA AB209630/miR-373/EphB2-NANOG signals. Bioscience reports 23 31147453
2014 EphB2 regulates contact-dependent and contact-independent signaling to control platelet function. Blood 23 25370417
2011 Expression profiling reveals MSX1 and EphB2 expression correlates with the invasion capacity of Wilms tumors. Pediatric blood & cancer 23 21387540
2013 MicroRNA-128 promotes cell-cell adhesion in U87 glioma cells via regulation of EphB2. Oncology reports 22 23835497
2019 Hypoxia-induced EPHB2 promotes invasive potential of glioblastoma. International journal of clinical and experimental pathology 21 31933858
2014 The Eph tyrosine kinase receptors EphB2 and EphA2 are novel proteolytic substrates of tissue factor/coagulation factor VIIa. The Journal of biological chemistry 21 25281742
2018 A mutation of the human EPHB2 gene leads to a major platelet functional defect. Blood 20 30213874
2017 Optogenetic activation of EphB2 receptor in dendrites induced actin polymerization by activating Arg kinase. Biology open 20 29158322
2016 Amygdala EphB2 Signaling Regulates Glutamatergic Neuron Maturation and Innate Fear. The Journal of neuroscience : the official journal of the Society for Neuroscience 20 27683910
2015 TNF-α/TNFR2 Regulatory Axis Stimulates EphB2-Mediated Neuroregeneration Via Activation of NF-κB. Journal of cellular physiology 20 26492598
2009 EphB2 and EphA4 receptors regulate formation of the principal inter-hemispheric tracts of the mammalian forebrain. Neuroscience 19 19289155
2007 Contribution by DRt descending facilitatory pathways to maintenance of spinal neuron sensitization in rats. Brain research 19 18054897
2020 Dual-Receptor-Targeted (DRT) Radiation Nanomedicine Labeled with 177Lu Is More Potent for Killing Human Breast Cancer Cells That Coexpress HER2 and EGFR Than Single-Receptor-Targeted (SRT) Radiation Nanomedicines. Molecular pharmaceutics 18 32022567
1998 Interaction of EphB2-tyrosine kinase receptor and its ligand conveys dorsalization signal in Xenopus laevis development. Oncogene 18 9794228
2018 Charge-Transfer Modeling and Polarization DRT Analysis of Proton Ceramics Fuel Cells Based on Mixed Conductive Electrolyte with the Modified Anode-Electrolyte Interface. ACS applied materials & interfaces 17 30251527
2017 Eps15R and clathrin regulate EphB2-mediated cell repulsion. Traffic (Copenhagen, Denmark) 17 28972287
2016 Identification of an Interfering Ligand Aptamer for EphB2/3 Receptors. Nucleic acid therapeutics 17 26824783
2022 EphrinB2/ephB2 activation facilitates colonic synaptic potentiation and plasticity contributing to long-term visceral hypersensitivity in irritable bowel syndrome. Life sciences 16 35183555
2020 Loss of tyrosine kinase receptor Ephb2 impairs proliferation and stem cell activity of spermatogonia in culture†. Biology of reproduction 16 31836902
2020 Synergistic antifibrotic effects of miR-451 with miR-185 partly by co-targeting EphB2 on hepatic stellate cells. Cell death & disease 16 32467578
2015 EphB1 and EphB2 intracellular domains regulate the formation of the corpus callosum and anterior commissure. Developmental neurobiology 16 26148571
2008 Germline EPHB2 receptor variants in familial colorectal cancer. PloS one 16 18682749
2024 ephrin-B2 promotes nociceptive plasticity and hyperalgesic priming through EphB2-MNK-eIF4E signaling in both mice and humans. Pharmacological research 15 38925462
2023 Fully integrated sample-in-answer-out platform for viral detection using digital reverse transcription recombinase polymerase amplification (dRT-RPA). Biosensors & bioelectronics 15 37352758
2019 EphB2 receptor cell-autonomous forward signaling mediates auditory memory recall and learning-driven spinogenesis. Communications biology 15 31633063
2014 EphB2 contributes to human naive B-cell activation and is regulated by miR-185. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 15 24803541

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