Affinage

EPHB3

Ephrin type-B receptor 3 · UniProt P54753

Length
998 aa
Mass
110.3 kDa
Annotated
2026-06-09
64 papers in source corpus 28 papers cited in narrative 28 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

EphB3 is an ephrin-B-family receptor tyrosine kinase that converts ephrinB3 engagement into bidirectional control of cell adhesion, migration, proliferation, and survival across epithelial, neural, and skeletal tissues (PMID:15536074, PMID:20496368, PMID:24810043). Upon ligand binding it autophosphorylates in trans at juxtamembrane tyrosines, with Tyr-614 serving as the principal docking site that recruits the SH2 adaptors rasGAP, Crk, and Fyn, while its C-terminal PDZ motif binds the Ras effector AF6 in a kinase-dependent manner (PMID:9674711, PMID:9707552, PMID:27478969). Active EphB3 nucleates downstream signaling complexes—assembling a RACK1–PP2A–Akt module that dampens Akt phosphorylation and migration in lung cancer (PMID:22314363), and rebalancing Rho-family GTPases by lowering Rac1/Cdc42 and raising RhoA to inhibit directional migration; this migratory restraint is kinase-independent whereas inhibition of integrin adhesion requires kinase activity (PMID:15536074). In epithelia EphB3 drives a mesenchymal-to-epithelial transition with restored E-cadherin and cell–cell adhesion and suppressed tumor growth, consistent with a role in intestinal compartmentalization that is set by Mule-dependent degradation of EphB3 protein (PMID:19483190, PMID:27184401). In the absence of ephrinB3, EphB3 behaves as a dependence receptor: it is cleaved by initiator caspases via the adaptor Dral/FHL-2 to trigger apoptosis in neurons, oligodendrocytes, and endothelial cells, and ligand binding blocks this death program—a mechanism conserved in human injury tissue (PMID:24810043, PMID:33305261, PMID:29311672). EphB3 also restrains neural stem/progenitor proliferation through p53 (PMID:20496368), and astrocytic EphB3 controls synaptic d-serine availability and NMDAR-dependent plasticity and memory (PMID:40081519). EPHB3 expression is tightly controlled transcriptionally—activated by an ASCL2/Wnt/Notch enhancer and silenced by SNAIL1-directed recruitment of LSD1/HDAC corepressors and by TCF7L1—and post-transcriptionally by YTHDF2-mediated m6A decay of its mRNA (PMID:24707046, PMID:25277775, PMID:27333864, PMID:35582627).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1998 High

    Establishing how ligand-activated EphB3 transmits a signal: identification of its autophosphorylation site and the adaptors it recruits defined the receptor's proximal signaling output.

    Evidence Site-directed mutagenesis (Y614F), in vitro binding, yeast two-hybrid and co-IP identifying rasGAP/Crk/Fyn at Y614 and kinase-dependent AF6 binding via the PDZ motif

    PMID:9674711 PMID:9707552

    Open questions at the time
    • Functional consequences of each adaptor downstream of Y614 not dissected
    • Whether AF6 phosphorylation alters its Ras-effector function not resolved
  2. 1998 Medium

    Defining the cognate ligand: ephrinB3 was shown to be a high-affinity, selective EphB3 ligand with midline expression, anchoring EphB3 in neural-tube patterning.

    Evidence Receptor-binding affinity assays (Kd ~1 nM) and in situ hybridization

    PMID:9484836

    Open questions at the time
    • In vivo developmental phenotype of this ligand-receptor pair not addressed here
    • Single-lab affinity measurement
  3. 2004 High

    Separating kinase-dependent from kinase-independent EphB3 outputs clarified that adhesion control needs catalytic activity but migration inhibition does not, mediated by GTPase rebalancing toward RhoA.

    Evidence WT vs kinase-dead stable lines, adhesion/migration assays, GTPase activity assays, pharmacological rescue

    PMID:15536074

    Open questions at the time
    • Molecular link between kinase-dead EphB3 and RhoA activation not identified
    • Effector GEF/GAP responsible not pinned down
  4. 2010 High

    Linking EphB3 to growth control: it suppresses neural stem/progenitor proliferation through p53 and induces death without ligand, foreshadowing its dependence-receptor behavior.

    Evidence EphB3-/- and ephrinB3-/- mice, BrdU/Ki67, ephrinB3-Fc infusion, p53 siRNA/inhibition epistasis

    PMID:20496368

    Open questions at the time
    • Mechanism connecting EphB3 to p53 induction unresolved
    • Cleavage machinery for ligand-free death not yet identified at this stage
  5. 2012 High

    Identifying RACK1 as an EphB3 partner showed how kinase-active receptor assembles a phosphatase-containing complex to suppress Akt and migration.

    Evidence Co-IP, forced kinase activation, in vitro migration and in vivo metastasis assays in NSCLC

    PMID:22314363

    Open questions at the time
    • How RACK1 is recruited to active EphB3 not detailed
    • Reconciliation with kinase-independent migration effects not addressed
  6. 2012 High

    Genetic epistasis distinguished forward from reverse signaling, establishing that EphB3 forward signaling drives palatal mesenchyme proliferation in development.

    Evidence Compound EphB2 truncation knockin / EphB3-null mice, palatal shelf culture, BrdU assays

    PMID:19032981

    Open questions at the time
    • Downstream proliferative effectors in palate not defined
    • EphB2/EphB3 redundancy boundaries not fully mapped
  7. 2014 High

    Defining EPHB3 transcriptional control: an ASCL2/Wnt/Notch enhancer activates the gene while SNAIL1 displaces ASCL2 and recruits LSD1/HDAC corepressors to silence it, explaining loss of EPHB3 in colorectal carcinoma.

    Evidence Enhancer/promoter reporter assays, ChIP for activators and repressors, Notch manipulation, xenografts with sustained EPHB3

    PMID:24707046 PMID:25277775

    Open questions at the time
    • Hierarchy among Wnt/Notch/MAPK inputs at the enhancer not fully ordered
    • In vivo relevance in human tumors beyond cell models limited
  8. 2014 High

    Establishing EphB3 as a dependence receptor: ligand-free EphB3 is caspase-cleaved to drive death, and ephrinB3 blocks cleavage to protect cells after brain injury.

    Evidence EphB3-/- and ephrinB3-/- mice, controlled cortical impact, TUNEL, caspase cleavage assays, ephrinB3-Fc rescue

    PMID:24810043

    Open questions at the time
    • Identity of the cleavage adaptor not yet known at this point
    • Threshold of ligand needed to suppress death not quantified
  9. 2016 Medium

    Multiple layers of EphB3 regulation and context-dependent signaling were defined: Mule-mediated degradation sets protein levels in the intestinal niche, TCF7L1 represses EPHB3 transcriptionally, and EphB3 can drive or suppress migration via Vav2/Rho GTPase rebalancing depending on context.

    Evidence Mule conditional KO with degradation-pathway inhibitors; TCF7L1 knockdown with EPHB3 epistasis; Vav2/GTPase activity assays in thyroid cancer

    PMID:27184401 PMID:27333864 PMID:27986811

    Open questions at the time
    • Reconciliation of pro- vs anti-migratory roles across tissues not unified
    • Single-lab findings for each regulatory axis
  10. 2016 High

    Mechanistic and structural definition of EphB3 catalysis: it autophosphorylates in trans, and a unique hinge cysteine enables covalent inhibitor targeting confirmed by co-crystal structures.

    Evidence Isoform-specific irreversible inhibitors, kinase assays, co-crystal structures, clickable probe

    PMID:27478969

    Open questions at the time
    • Cellular consequences of selective EphB3 inhibition in disease not tested here
    • Whether trans-autophosphorylation requires specific receptor clustering geometry unresolved
  11. 2020 High

    Completing the dependence-receptor mechanism: EphB3 recruits initiator caspases and the adaptor Dral/FHL-2 to execute cleavage-dependent death, with the pathway conserved in human TBI tissue.

    Evidence Co-IP with FHL-2/caspases, caspase cleavage assays, EphB3-/- mice, ephrinB3-Fc rescue, human tissue analysis

    PMID:33305261

    Open questions at the time
    • Structural basis of FHL-2/caspase recruitment to EphB3 not solved
    • Whether the same adaptor operates in non-CNS cell types not established
  12. 2022 Medium

    Post-transcriptional control was extended: YTHDF2-mediated m6A decay of EPHB3 mRNA lowers protein levels and activates PI3K/Akt and NF-κB to promote glioblastoma drug resistance.

    Evidence RNA-IP, FISH, dual-luciferase 3'UTR reporter, YTHDF2 knockdown, pathway-inhibitor rescue

    PMID:35582627

    Open questions at the time
    • Whether EphB3 protein loss alone, versus other YTHDF2 targets, drives the pathway activation not isolated
    • Single-lab study
  13. 2025 High

    Defining a non-canonical CNS function: astrocytic EphB3 controls synaptic d-serine availability to set NMDAR-dependent plasticity and memory, with d-serine rescuing loss-of-function deficits.

    Evidence Astrocyte-specific EphB3 knockdown, slice LTP electrophysiology, d-serine measurement and rescue, novel object recognition

    PMID:40081519

    Open questions at the time
    • Signaling link from EphB3 to d-serine synthesis/release not delineated
    • Relationship to EphB3's neuronal dependence-receptor role not integrated

Open questions

Synthesis pass · forward-looking unresolved questions
  • How EphB3 switches between kinase-dependent signaling, kinase-independent migration control, and ligand-free dependence-receptor death within a single cell, and what determines its opposing pro- versus anti-tumor outputs across tissues, remains unresolved.
  • No unified model reconciling context-specific migratory and survival outputs
  • Structural basis for the death-versus-signaling switch unknown
  • In vivo therapeutic targeting consequences untested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 4 GO:0060089 molecular transducer activity 3 GO:0016740 transferase activity 2 GO:0001618 virus receptor activity 1
Localization
GO:0005886 plasma membrane 3
Pathway
R-HSA-162582 Signal Transduction 4 R-HSA-5357801 Programmed Cell Death 4 R-HSA-1266738 Developmental Biology 3 R-HSA-74160 Gene expression (Transcription) 3
Partners
AF6CRKEFNB3EGFRFHL2FYNRACK1RASA1
Complex memberships
EphB3-FHL-2/Dral-caspase death complexRACK1-PP2A-Akt complex

Evidence

Reading pass · 28 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 EphB3 (HEK2) interacts via its C-terminal PDZ-binding motif with the PDZ domain of the Ras-binding protein AF6; this interaction with full-length AF6 (but not the isolated PDZ domain) depends on EphB3 kinase activity. Endogenous AF6 is phosphorylated by EphB3 and EphB2 in a ligand-dependent fashion in NIH 3T3 and NG108 cells. Yeast two-hybrid, mutational analysis, immunoprecipitation, in-cell phosphorylation assays Proceedings of the National Academy of Sciences of the United States of America High 9707552
1998 Tyrosine-614 (Y614) is the major autophosphorylation site of EphB3 (HEK2) and functions as a multi-docking site for SH2-domain-containing proteins rasGAP (via its N-terminal SH2 domain), Crk, and Fyn; a Y614F substitution abolishes binding of all three. In vitro binding assays, immunoprecipitation, yeast two-hybrid, site-directed mutagenesis (Y614F) Oncogene High 9674711
1998 Ephrin-B3 is a high-affinity ligand for EphB3 (Kd ~1 nM) with selectivity among the transmembrane ephrin-B family; it is expressed at the dorsal and ventral midline of the neural tube (floor plate). Receptor-binding affinity assays, in situ hybridization Oncogene Medium 9484836
2002 Human RYK associates with EphB2 and EphB3, requiring both extracellular and cytoplasmic domains of RYK; this association is not dependent on Eph receptor activation. Unlike murine Ryk, human RYK is not phosphorylated by EphB3. Co-immunoprecipitation, in vitro binding assays The Journal of biological chemistry Medium 11956217
2004 EphB3 kinase activity is required for inhibition of integrin-mediated cell adhesion and induction of cell rounding, but directional cell migration inhibition is kinase-independent. Both wild-type and kinase-dead EphB3 reduce Rac1 and Cdc42 activity upon ephrin-B1 stimulation, with a relative increase in RhoA signaling mediating migration inhibition. Stable transfection of WT vs. kinase-dead EphB3, adhesion assays, migration assays, GTPase activity assays, pharmacological inhibition, integrin-activating antibodies The Journal of biological chemistry High 15536074
2006 EphB3 expressed by recruited macrophages at the optic nerve injury site supports adult retinal ganglion cell (RGC) axon re-extension and sprouting after injury; loss of EphB3 greatly decreases axon plasticity without affecting intrinsic axon growth potential. Injured RGC axons express EphrinB3 and bind recombinant EphB3 protein in vivo. In vivo optic nerve injury in EphB3 heterozygous and null mice, mRNA expression analysis, recombinant protein injection, in vitro axon outgrowth and turning assays The Journal of neuroscience High 16554460
2009 EphB3 overexpression in HT-29 colorectal cancer cells promotes mesenchymal-to-epithelial transition (MET): reorganizes cortical actin, increases E-cadherin/ZO-1/plakoglobin, decreases fibronectin and nuclear β-catenin, inactivates CrkL-Rac1, increases Ca2+-dependent cell-cell adhesion, and suppresses tumor growth in xenografts. Stable transfection, morphological analysis, immunofluorescence, transwell migration, soft agar assay, xenograft, GTPase assays Carcinogenesis Medium 19483190
2010 EphB3 signaling suppresses neural stem/progenitor cell (NSPC) proliferation in the subventricular zone in a p53-dependent manner. EphB3 activation by ephrinB3-Fc increases p53 expression; pharmacological inhibition or siRNA knockdown of p53 attenuates ephrinB3-Fc-mediated growth suppression. In the absence of ligand, EphB3 induces cell death. EphB3-/- and ephrinB3-/- knockout mice, BrdU incorporation, Ki67 immunostaining, lateral ventricle ephrinB3-Fc infusion, siRNA knockdown of p53, pharmacological p53 inhibition, cultured NSPCs Stem cells High 20496368
2011 In NSCLC cells, EphB3 promotes cell growth and migration in a kinase-independent manner when overexpressed; silencing EphB3 reduces DNA synthesis, activates caspase-8-mediated apoptosis, and increases focal adhesion accumulation to suppress migration. Stable overexpression and siRNA knockdown in NSCLC cell lines, proliferation/migration assays, xenograft models, apoptosis assays, focal adhesion staining Cancer research Medium 21266352
2012 Kinase-activated EphB3 in NSCLC assembles a ternary signaling complex comprising RACK1, PP2A, and Akt, leading to reduced Akt phosphorylation and inhibition of cell migration. RACK1 mediates assembly of this complex in response to EphB3 activation. Co-immunoprecipitation, forced EphB3 kinase activation, in vitro migration assay, in vivo metastasis seeding, identification of RACK1 as EphB3-binding protein Nature communications High 22314363
2012 EphB2 and EphB3 forward signaling (not reverse signaling) are required for palatal mesenchyme proliferation and palate development; foetuses with cytoplasmic-truncated EphB2 (capable of reverse but not forward signaling) plus EphB3-null develop cleft palate due to reduced palatal shelf proliferation. Genetic epistasis using kinase-dead/truncated EphB2 knockin and EphB3-/- compound mutant mice, palatal shelf culture, BrdU proliferation assays Mechanisms of development High 19032981
2014 SNAIL1 silences EPHB3 by competitively displacing the stem cell factor ASCL2 from an E-box motif in the EPHB3 promoter/enhancer, then recruiting corepressor complexes containing HDACs and the histone demethylase LSD1, collapsing active chromatin. SNAIL2, but not ZEB1, also represses EPHB3 reporter constructs. Reporter assays, ChIP for ASCL2/p300/TCF7L2/LSD1/HDACs, endogenous locus analysis, xenotransplant models with/without sustained EPHB3 expression Molecular oncology High 25277775
2014 A transcriptional enhancer at the EPHB3 locus integrates input from ASCL2, Wnt/β-catenin, MAP kinase, and Notch signaling; low Notch activity causes enhancer decommissioning and EPHB3 silencing in colorectal carcinoma. Restoring Notch activity re-establishes enhancer function and EPHB3 expression. Enhancer reporter assays, ChIP, Notch pathway manipulation, gene expression analysis in cell lines and tumors Proceedings of the National Academy of Sciences of the United States of America High 24707046
2014 EphB3 functions as a dependence receptor in neurons: in the absence of ephrinB3 ligand, EphB3 is cleaved by caspases and induces cell death; ephrinB3 stimulation blocks this cleavage and prevents apoptosis. Infusion of clustered ephrinB3-Fc reduces cortical infarct and cell death after controlled cortical impact injury via EphB3-dependent mechanism. EphB3-/- and ephrinB3-/- mice, controlled cortical impact injury, TUNEL staining, ephrinB3-Fc infusion, caspase cleavage assays Cell death & disease High 24810043
2015 EphB3 mediates oligodendrocyte cell death in the injured spinal cord through a dependence receptor mechanism; ephrinB3 ligand administration promotes oligodendrocyte survival both in vivo and in vitro under pro-apoptotic conditions. Genetic ablation of EphB3 increases myelin basic protein expression and improves locomotor function after SCI. EphB3-/- mice, contusive spinal cord injury, oligodendrocyte survival assays, ephrinB3 ligand administration, locomotor behavioral assessment Cell death & disease High 26469970
2016 TCF7L1 represses EPHB3 expression in colorectal cancer cells; loss of TCF7L1 activates EPHB3 as a CTNNB1/TCF target gene. Knockdown of EPHB3 partially restores growth and normal cell cycle progression in TCF7L1-null CRC cells. TCF7L1 knockdown/knockout in CRC cells, gene expression analysis, EPHB3 siRNA epistasis, xenograft tumor models, colony formation assays Scientific reports Medium 27333864
2016 EphB3 stimulates migration and metastasis in papillary thyroid cancer in a kinase-dependent manner through activation of Vav2, a Rho GEF, leading to increased Rac1 activity and decreased RhoA activity. EphB3 knockdown suppresses Vav2 and reverses this GTPase balance. siRNA knockdown, EphB3 overexpression, ephrin-B1/B2-Fc stimulation, EphB3-Fc blocking, Rho GTPase activity assays, in vivo metastasis model The Journal of biological chemistry Medium 27986811
2016 The Mule E3 ubiquitin ligase targets EphB3 for proteasomal and lysosomal degradation in the intestinal stem cell niche, controlling EphB3 protein levels and thus crypt-villus cell positioning. In vivo mouse genetics (Mule conditional KO), western blotting, proteasome/lysosome inhibitor treatment Cell stem cell Medium 27184401
2016 EphB3 receptors in the juxtamembrane region undergo autophosphorylation in trans (not in cis), demonstrated using isoform-specific covalent inhibitors; a unique cysteine in the EphB3 hinge region (absent in other human kinases) allows covalent inhibitor targeting. Co-crystal structures confirmed covalent linkage between EphB3 and quinazoline inhibitors. Specific irreversible inhibitor synthesis, kinase assays, co-crystal structures, 'clickable' inhibitor for proteome-wide target engagement Journal of the American Chemical Society High 27478969
2016 EphB3 signaling in the hippocampus after traumatic brain injury promotes synaptic loss and reduces d-serine levels; EphB3-/- mice show preserved long-term potentiation, improved hippocampal-dependent learning, and attenuated synapse loss and d-serine reduction compared to wild-type injured mice. EphB3-/- mice, controlled cortical impact injury, LTP electrophysiology, synaptic protein quantification, d-serine measurement, behavioral learning assays Neurobiology of disease Medium 27317833
2018 EphB3 functions as a pro-apoptotic dependence receptor in cortical endothelial cells after TBI; in the absence of EphB3, endothelial cell survival is increased, blood-brain barrier permeability is reduced, and astrocyte-EC membrane interactions are enhanced after controlled cortical impact. EphB3-/- mice, CCI injury, BBB permeability assays, endothelial cell survival quantification, immunofluorescence of astrocyte-EC contacts Cell death & disease Medium 29311672
2018 EphB3 suppresses glioma invasion, migration, and proliferation by downregulating the EGFR-PI3K/AKT signaling pathway; EphB3 knockdown upregulates EGFR, p-PI3K, and p-AKT, while overexpression downregulates these proteins. siRNA knockdown and overexpression in U87MG and U251 glioma cell lines, western blotting, invasion/migration/proliferation assays Brain research Medium 38341169
2019 In cetuximab-resistant colorectal cancer, EGFR and EphB3 physically interact (co-immunoprecipitation), and this binding increases upon resistance acquisition, leading to STAT3 activation; inhibition of EphB3 decreases STAT3 activity. Co-immunoprecipitation, western blotting for STAT3 phosphorylation, RTK array, siRNA knockdown, cetuximab-resistant cell line model Theranostics Medium 31149041
2020 EphB3 interacts with initiator caspases (caspase-8 or caspase-9) and the adaptor protein Dral/FHL-2 to mediate its cleavage and activate dependence receptor cell death in oligodendrocytes after brain injury; blocking this pathway with ephrinB3-Fc improves oligodendrocyte survival, myelin sparing, axonal conductance, and behavioral recovery in mice and conserved mechanism found in human TBI patients. Co-immunoprecipitation, caspase cleavage assays, EphB3-/- mice, CCI injury, ephrinB3-Fc administration, behavioral/electrophysiological readouts, human TBI tissue analysis Brain communications High 33305261
2022 YTHDF2 binds to m6A sites in the 3'UTR of EPHB3 mRNA to decrease its stability and reduce EPHB3 protein levels, thereby activating the PI3K/Akt and NF-κB signaling pathways and promoting temozolomide resistance in glioblastoma. RNA immunoprecipitation, FISH, dual-luciferase reporter, siRNA knockdown of YTHDF2, RNA sequencing, rescue experiments with PI3K/Akt and NF-κB inhibitors Clinical & translational immunology Medium 35582627
2024 EphB3 acts as a negative regulator of osteogenic differentiation in mesenchymal stromal/stem cells; absence of EphB3 signaling reduces expression of BMP pathway inhibitors, increases Bmp7 expression, increases osteoprogenitor and preosteoblast proportions, and reduces osteoclast numbers, preventing bone loss in ovariectomy and glucocorticoid-induced osteoporosis mouse models. EphB3-/- and EphB2-/- mice, in vitro MSC differentiation assays, qRT-PCR, histological staining, ovariectomy and dexamethasone bone loss models, bone volume/density measurement Journal of bone and mineral research Medium 38739682
2025 Astrocytic EphB3 receptors regulate synaptic d-serine availability at CA3-CA1 hippocampal synapses: stimulation of EphB3 with exogenous ephrinB3 increases d-serine and NMDAR activity, while inhibition of endogenous EphB3 impairs NMDAR-dependent LTP. Astrocyte-specific knockdown of EphB3 causes hippocampal plasticity deficits and novel object recognition memory impairment that can be rescued by exogenous d-serine. Acute hippocampal slice electrophysiology, exogenous ephrinB3 application, EphB3 inhibition, astrocyte-specific EphB3 knockdown, d-serine measurement, LTP recording, behavioral memory testing Progress in neurobiology High 40081519
2025 MHV68 gH/gL glycoprotein complex directly interacts with EphB3 (and EphA4), enabling viral entry; ectopic expression of EphB3 enables MHV68 infection of otherwise non-permissive human B cells, demonstrating EphB3 functions as an entry receptor for this gammaherpesvirus. Direct binding assays, ectopic EphB3 expression in non-permissive B cells, soluble decoy receptor competition, mutagenesis informed by structural predictions, neutralizing antibody adsorption bioRxivpreprint Medium bio_10.1101_2025.06.05.657996

Source papers

Stage 0 corpus · 64 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1998 PDZ-domain-mediated interaction of the Eph-related receptor tyrosine kinase EphB3 and the ras-binding protein AF6 depends on the kinase activity of the receptor. Proceedings of the National Academy of Sciences of the United States of America 176 9707552
2012 EphB3 suppresses non-small-cell lung cancer metastasis via a PP2A/RACK1/Akt signalling complex. Nature communications 110 22314363
2011 EphB3 is overexpressed in non-small-cell lung cancer and promotes tumor metastasis by enhancing cell survival and migration. Cancer research 95 21266352
2004 Inhibition of integrin-mediated cell adhesion but not directional cell migration requires catalytic activity of EphB3 receptor tyrosine kinase. Role of Rho family small GTPases. The Journal of biological chemistry 84 15536074
2009 Over-expression of EphB3 enhances cell-cell contacts and suppresses tumor growth in HT-29 human colon cancer cells. Carcinogenesis 81 19483190
2006 EphB3: an endogenous mediator of adult axonal plasticity and regrowth after CNS injury. The Journal of neuroscience : the official journal of the Society for Neuroscience 65 16554460
1998 Ephrin-B3, a ligand for the receptor EphB3, expressed at the midline of the developing neural tube. Oncogene 64 9484836
2010 EphB3 limits the expansion of neural progenitor cells in the subventricular zone by regulating p53 during homeostasis and following traumatic brain injury. Stem cells (Dayton, Ohio) 63 20496368
2009 Identification of novel candidate target genes, including EPHB3, MASP1 and SST at 3q26.2-q29 in squamous cell carcinoma of the lung. BMC cancer 63 19607727
1998 Tyrosine-614, the major autophosphorylation site of the receptor tyrosine kinase HEK2, functions as multi-docking site for SH2-domain mediated interactions. Oncogene 52 9674711
2018 Formononetin inhibits colon carcinoma cell growth and invasion by microRNA‑149‑mediated EphB3 downregulation and inhibition of PI3K/AKT and STAT3 signaling pathways. Molecular medicine reports 49 29620230
2008 EphB2 and EphB3 forward signalling are required for palate development. Mechanisms of development 47 19032981
2003 Transection of the adult rat spinal cord upregulates EphB3 receptor and ligand expression. Cell transplantation 43 12797382
2016 TCF7L1 Modulates Colorectal Cancer Growth by Inhibiting Expression of the Tumor-Suppressor Gene EPHB3. Scientific reports 41 27333864
2014 SNAIL1 combines competitive displacement of ASCL2 and epigenetic mechanisms to rapidly silence the EPHB3 tumor suppressor in colorectal cancer. Molecular oncology 40 25277775
2002 RYK, a catalytically inactive receptor tyrosine kinase, associates with EphB2 and EphB3 but does not interact with AF-6. The Journal of biological chemistry 39 11956217
2019 Sonic hedgehog pathway activation is associated with cetuximab resistance and EPHB3 receptor induction in colorectal cancer. Theranostics 34 31149041
2014 Silencing of the EPHB3 tumor-suppressor gene in human colorectal cancer through decommissioning of a transcriptional enhancer. Proceedings of the National Academy of Sciences of the United States of America 34 24707046
2016 Development of Specific, Irreversible Inhibitors for a Receptor Tyrosine Kinase EphB3. Journal of the American Chemical Society 30 27478969
2016 EphB3 signaling propagates synaptic dysfunction in the traumatic injured brain. Neurobiology of disease 29 27317833
2014 EphrinB3 blocks EphB3 dependence receptor functions to prevent cell death following traumatic brain injury. Cell death & disease 28 24810043
2018 EphB3 signaling induces cortical endothelial cell death and disrupts the blood-brain barrier after traumatic brain injury. Cell death & disease 27 29311672
2016 Mule Regulates the Intestinal Stem Cell Niche via the Wnt Pathway and Targets EphB3 for Proteasomal and Lysosomal Degradation. Cell stem cell 26 27184401
2012 EphB3 marks delaminating endocrine progenitor cells in the developing pancreas. Developmental dynamics : an official publication of the American Association of Anatomists 24 22434763
2009 Structure-activity relationship study of EphB3 receptor tyrosine kinase inhibitors. Bioorganic & medicinal chemistry letters 24 19783434
2016 EphB3 Stimulates Cell Migration and Metastasis in a Kinase-dependent Manner through Vav2-Rho GTPase Axis in Papillary Thyroid Cancer. The Journal of biological chemistry 23 27986811
2018 EZH2-mediated epigenetic suppression of EphB3 inhibits gastric cancer proliferation and metastasis by affecting E-cadherin and vimentin expression. Gene 22 30408551
2010 Neural progenitors proliferation is inhibited by EphB3 in the developing subventricular zone. International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience 22 20969945
2001 Expression of the receptor tyrosine kinase gene EphB3 during early stages of chick embryo development. Mechanisms of development 22 11404090
2018 Upregulation of EphB3 in gastric cancer with acquired resistance to a FGFR inhibitor. The international journal of biochemistry & cell biology 21 30044964
2016 Up-regulated ephrinB3/EphB3 expression in intractable temporal lobe epilepsy patients and pilocarpine induced experimental epilepsy rat model. Brain research 19 26930615
2017 EphB3-targeted regulation of miR-149 in the migration and invasion of human colonic carcinoma HCT116 and SW620 cells. Cancer science 18 28370854
1995 Identification of alternative exons, including a novel exon, in the tyrosine kinase receptor gene Etk2/tyro3 that explain differences in 5' cDNA sequences. Oncogene 18 7784069
2012 Roles of EphB3/ephrin-B1 in feather morphogenesis. The International journal of developmental biology 16 23319347
2006 EphB3 receptor and ligand expression in the adult rat brain. Journal of molecular histology 16 17103029
2019 Luteolin-7-O-β-d-Glucoside Inhibits Cellular Energy Production Interacting with HEK2 in Keratinocytes. International journal of molecular sciences 15 31159225
2015 EphB3 receptors function as dependence receptors to mediate oligodendrocyte cell death following contusive spinal cord injury. Cell death & disease 15 26469970
2022 YTHDF2 promotes temozolomide resistance in glioblastoma by activation of the Akt and NF-κB signalling pathways via inhibiting EPHB3 and TNFAIP3. Clinical & translational immunology 14 35582627
2020 Long noncoding RNA HAS2-AS1 accelerates non-small cell lung cancer chemotherapy resistance by targeting LSD1/EphB3 pathway. American journal of translational research 13 32269726
2009 Cell-autonomous role of EphB2 and EphB3 receptors in the thymic epithelial cell organization. European journal of immunology 13 19731361
2021 Low Expression of EphB2, EphB3, and EphB4 in Bladder Cancer: Novel Potential Indicators of Muscular Invasion. Yonsei medical journal 12 34296545
2015 EphB2 and EphB3 play an important role in the lymphoid seeding of murine adult thymus. Journal of leukocyte biology 12 25810451
2017 EphB3 protein is associated with histological grade and FIGO stage in ovarian serous carcinomas. APMIS : acta pathologica, microbiologica, et immunologica Scandinavica 10 28120491
2017 EphB receptors, mainly EphB3, contribute to the proper development of cortical thymic epithelial cells. Organogenesis 10 29027839
2021 Hit Identification of a Novel Quinazoline Sulfonamide as a Promising EphB3 Inhibitor: Design, Virtual Combinatorial Library, Synthesis, Biological Evaluation, and Docking Simulation Studies. Pharmaceuticals (Basel, Switzerland) 9 34959648
2018 Role of EphB3 Receptor in Mediating Head and Neck Tumor Growth, Cell Migration, and Response to PI3K Inhibitor. Molecular cancer therapeutics 9 29970482
2025 Astrocytic EphB3 receptors regulate d-serine-gated synaptic plasticity and memory. Progress in neurobiology 6 40081519
2007 Epistatic interaction between the K-homology domain protein HEK2 and SIR1 at HMR and telomeres in yeast. Journal of molecular biology 6 18067921
2000 ETK2 receptor tyrosine kinase promotes survival of factor-dependent FDC-P1 progenitor cells. Experimental hematology 6 10880758
2023 Up-regulated lncRNA SNHG9 mediates the pathogenesis of dilated cardiomyopathy via miR-326/EPHB3 axis. Journal of thrombosis and thrombolysis 5 37004604
2024 Circular RNA circRest regulates manganese induced cell apoptosis by targeting the mmu-miR-6914-5p/Ephb3 axis. Environmental pollution (Barking, Essex : 1987) 4 38266697
2024 EphB3 receptor suppressor invasion, migration and proliferation in glioma by inhibiting EGFR-PI3K/AKT signaling pathway. Brain research 4 38341169
2024 The lack of EphB3 receptor prevents bone loss in mouse models of osteoporosis. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 4 38739682
2020 EphB3 interacts with initiator caspases and FHL-2 to activate dependence receptor cell death in oligodendrocytes after brain injury. Brain communications 4 33305261
2025 miR-330-5p Attenuates Isoflurane-Induced Neuroinflammation and Cognitive Dysfunction by Regulating EPHB3. Synapse (New York, N.Y.) 3 40433993
2025 Discovery of pan-EphB tyrosine kinase inhibitor for metabolic syndrome sparing EphB3 signaling in mice. Pharmacological research 3 40769385
2022 Knockdown of EphB3 inhibits cell proliferation partly through the AKT signaling pathway and represses epithelial-mesenchymal transition in esophageal squamous cell carcinoma. Translational cancer research 3 35261887
2021 EphB3 as a Potential Mediator of Developmental and Reparative Osteogenesis. Cells, tissues, organs 3 34695818
2023 Role and mechanism of EphB3 in epileptic seizures and epileptogenesis through Kalirin. Molecular and cellular neurosciences 2 38143048
2023 EphB3 protein is a potential ancillary diagnostic biomarker for thyroid cancers. Annals of diagnostic pathology 2 38150866
2025 Penta-1,4-dien-3-one and quinoxaline conjugates as potential anticancer agents via inhibiting EphB3/SRC/AKT axis. Life sciences 1 40021052
2026 Establishment of Novel Anti-EphB3 Monoclonal Antibodies for Multiple Applications. Monoclonal antibodies in immunodiagnosis and immunotherapy 0 41468102
2025 Tissue microarray and liquid biopsy approaches identify EphB3, cMet, and miR-3168 as biomarkers of colorectal cancer. Cell cycle (Georgetown, Tex.) 0 40790791
2024 Peripheral T-cell responses of EphB2- and EphB3-deficient mice in a model of collagen-induced arthritis. Cellular and molecular life sciences : CMLS 0 38558087

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