Affinage

EPHB1

Ephrin type-B receptor 1 · UniProt P54762

Length
984 aa
Mass
109.9 kDa
Annotated
2026-06-09
64 papers in source corpus 33 papers cited in narrative 33 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

EphB1 is an ephrin-B-activated receptor tyrosine kinase that, upon ligand engagement and autophosphorylation, assembles phosphotyrosine-dependent adaptor complexes to control cell adhesion, migration, and actin cytoskeletal dynamics (PMID:10205170, PMID:9430661, PMID:12925710). Activated EphB1 recruits the SH2-adaptor Nck through phospho-Tyr594 to drive JNK activation and cell attachment, and the Nck–paxillin/FAK axis with c-Src-dependent paxillin phosphorylation to promote migration (PMID:9430661, PMID:15107421); it also engages Grb2/p52Shc and Grb7 through distinct phosphotyrosines (Tyr600/Tyr778, Tyr928) to activate ERK/MAPK and chemotaxis (PMID:12925710, PMID:12223469), and recruits the scaffold Caskin1 via Nck (PMID:23181695). Forward signaling brakes axon outgrowth by binding the RhoGAP Porf-2 to deactivate Rac1 (PMID:29938386), while PTEN, delivered through NHERF1, antagonizes EphB1-dependent adhesion and chemotaxis (PMID:23118026). EphB1 is a principal determinant of neural circuit wiring: it functions as the preferred receptor for ephrin-B2 at the optic chiasm, where its kinase-competent forward signaling repels ventrotemporal retinal ganglion cell axons to establish the ipsilateral projection downstream of the Zic2 transcription factor (PMID:12971893, PMID:18524895, PMID:19295152, PMID:22103419), and it directs neural crest migration, dopaminergic pathway specification, and forebrain commissural and long-range cortical axon guidance—the latter cell-autonomously through GABAergic neurons (PMID:9259557, PMID:10066262, PMID:17561836, PMID:26148571, PMID:38345254). EphB1 localizes to caveolae and is required for caveolae biogenesis by constitutively binding and stabilizing caveolin-1 against ubiquitin-mediated degradation (PMID:16723736, PMID:32238105). Its abundance and activity are tuned post-translationally—by Cbl-mediated ubiquitination and lysosomal degradation (PMID:18034775), SUMOylation at Lys785 that suppresses PKCγ and tumor growth (PMID:29550816), and neddylation that stabilizes the receptor and enhances kinase activity (PMID:36834826). Kinase-dependent EphB1 acts as a tumor suppressor: cancer-associated somatic mutations reduce its activity, stability, and ability to compartmentalize cells, and re-expression of EphB1 in silenced leukemia cells enforces a p53-driven DNA-damage/apoptotic program (PMID:25944917, PMID:37527777, PMID:38102712).

Mechanistic history

Synthesis pass · year-by-year structured walk · 25 steps
  1. 1998 High

    Established the first proximal EphB1 effector linkage by showing how a defined receptor phosphotyrosine couples kinase activation to a downstream MAP kinase and an adhesive cell response.

    Evidence Yeast two-hybrid, Co-IP, Y594F mutagenesis, JNK and cell attachment assays

    PMID:9430661

    Open questions at the time
    • Did not define the kinase chain from Nck to JNK
    • Physiological cell context of the attachment response not addressed
  2. 1999 High

    Defined EphB1 as a ligand-density sensor whose kinase signaling, not mechanical tethering, converts ephrin-B engagement into integrin-mediated attachment.

    Evidence Reconstituted ephrin-B1 surface-density assay with integrin blocking and signaling-defective EphB1 mutants

    PMID:10205170

    Open questions at the time
    • Mechanism coupling EphB1 to specific integrins not resolved
    • Tested in endothelial and transfected HEK cells only
  3. 2002 High

    Mapped a second adaptor branch by identifying Grb7 as an autophosphorylation-dependent EphB1 partner and substrate that drives motility.

    Evidence Yeast two-hybrid, Co-IP, Tyr928 mutagenesis, kinase and migration assays

    PMID:12223469

    Open questions at the time
    • Downstream effectors of Grb7 in EphB1 migration unresolved
  4. 2003 High

    Resolved the EphB1 migration pathway by linking Tyr600/Tyr778, c-Src, p52Shc and ERK to chemotaxis as distinct from adhesion.

    Evidence Co-IP, Y600F/Y778F mutagenesis, dominant-negative Src, PD98059/PP2 inhibitors, migration vs adhesion assays

    PMID:12925710

    Open questions at the time
    • Spatial coordination of parallel adhesion and migration outputs not defined
  5. 2003 High

    Demonstrated that EphB1 forward signaling drives a specific developmental axon-sorting decision, establishing its role in binocular circuit formation.

    Evidence EphB1 knockout mice, expression mapping, ephrin-B2 function-blocking in semiintact visual system

    PMID:12971893

    Open questions at the time
    • Intracellular effectors mediating chiasm repulsion not identified in this study
  6. 2004 High

    Built the EphB1→Nck→paxillin/FAK→Src migration complex, connecting the juxtamembrane adaptor to focal-adhesion substrate phosphorylation.

    Evidence Co-IP, paxillin Y31F/Y118F and EphB1 Y594F mutagenesis, dominant-negative Src, PP2, migration assay

    PMID:15107421

    Open questions at the time
    • Whether the complex acts at nascent versus mature adhesions unresolved
  7. 2006 Medium

    Placed EphB1 in caveolae and tied its membrane targeting and ERK output to a caveolin-binding motif in the kinase domain.

    Evidence Fractionation, Co-IP, Cav-1 scaffolding-domain mutant, confocal microscopy, ERK assays

    PMID:16723736

    Open questions at the time
    • Did not determine whether caveolae are required for all EphB1 signaling outputs
  8. 2007 High

    Defined the negative-feedback arm of EphB1 signaling through Cbl-mediated ubiquitination and lysosomal turnover.

    Evidence Co-IP, GST pull-down, Cbl ligase-dead and EphB1-K652R mutants, ubiquitination assay, bafilomycin, PP2

    PMID:18034775

    Open questions at the time
    • Kinetics of receptor recycling versus degradation not quantified
  9. 2008 High

    Identified the transcriptional control point upstream of EphB1 by showing Zic2 induces functional EphB1 to convert axon behavior to ephrin-B2 avoidance.

    Evidence Retinal explant electroporation, avoidance assays on ephrin-B2, growth-cone immunofluorescence

    PMID:18524895

    Open questions at the time
    • Direct versus indirect regulation of the EphB1 promoter by Zic2 not established
  10. 2009 High

    Showed EphB1 is both necessary and sufficient for ipsilateral redirection and that its specificity resides in extracellular and juxtamembrane domains.

    Evidence In utero retinal electroporation, EphB1-EphB2 chimeric receptors, in vivo tracing

    PMID:19295152

    Open questions at the time
    • Molecular basis of domain-specific specificity over EphB2 not defined at residue level
  11. 2011 High

    Distinguished forward from reverse signaling, proving EphB1 intracellular signaling drives the ipsilateral projection.

    Evidence Intracellular-truncated EphB1 knock-in mice, axon tracing, EphB/ephrin-B genetic combinations

    PMID:22103419

    Open questions at the time
    • Effector cascade downstream of forward signal in RGCs not fully mapped
  12. 2012 Medium

    Extended EphB1 adaptor wiring by identifying Caskin1 as a Nck-bridged substrate undergoing phosphorylation-induced conformational change.

    Evidence Co-IP, mass-spectrometry phosphosite mapping, CD spectroscopy

    PMID:23181695

    Open questions at the time
    • Functional consequence of Caskin1 phosphorylation for EphB1 output untested
  13. 2012 Medium

    Revealed PTEN/NHERF1 as a phosphatase brake that disrupts the PTEN-Cbl complex and limits EphB1-driven adhesion and chemotaxis.

    Evidence Co-IP, PTEN and NHERF1 siRNA, PTEN phosphatase mutants, adhesion and chemotaxis assays

    PMID:23118026

    Open questions at the time
    • In vivo relevance of the PTEN-Cbl switch not addressed
  14. 2018 Medium

    Identified the RhoGAP Porf-2 as the link between EphB1 forward signaling and Rac1 inactivation in axon-growth braking.

    Evidence Co-IP, GTP-Rac1 pull-down, GAP-domain mutagenesis, axon growth measurement

    PMID:29938386

    Open questions at the time
    • Recruitment mechanism of Porf-2 to activated EphB1 unresolved
  15. 2018 Medium

    Established SUMOylation at Lys785 as a tumor-suppressive post-translational switch that represses PKCγ.

    Evidence Ni-NTA/IP SUMOylation assay, K785R mutant, soft-agar and xenograft assays, PKCγ activation assay

    PMID:29550816

    Open questions at the time
    • SUMO ligase responsible not identified
    • Relationship to kinase activity not defined
  16. 2020 High

    Demonstrated that EphB1 constitutively stabilizes caveolin-1 and is required for caveolae biogenesis in endothelial cells.

    Evidence Super-resolution microscopy, FRET, Co-IP, CSD-motif deletion mutant, EphB1-KO ECs, EM caveolae counting

    PMID:32238105

    Open questions at the time
    • Physiological vascular consequences of caveolae loss not assessed
  17. 2020 Medium

    Uncovered phosphorylation-state-dependent dual function: ligand-independent EphB1 promotes EMT while activated EphB1 inhibits invasion, downstream of TGF-β/Smad2.

    Evidence EphB1 phosphorylation mutants, Smad2/CDH2 western blot, transwell assays, siRNA

    PMID:32368295

    Open questions at the time
    • Mechanism by which unphosphorylated EphB1 upregulates N-cadherin unclear
  18. 2021 High

    Provided a structural and pharmacological handle by co-crystallizing a tetracycline in the EphB1 ATP pocket and blocking neuropathic pain in vivo.

    Evidence In silico docking, in vitro kinase assay, X-ray co-crystallography, in vivo phosphorylation and pain model

    PMID:33627480

    Open questions at the time
    • Selectivity over related Eph kinases not fully characterized
  19. 2023 High

    Established EphB1 kinase activity as essential for its tumor-suppressor function, with cancer mutations crippling activity, stability and cell compartmentalization.

    Evidence Purified WT/mutant kinase-domain assays, migration and compartmentalization assays in CRC cells

    PMID:37527777

    Open questions at the time
    • In vivo tumor-suppressor validation of specific mutants not shown
  20. 2023 Medium

    Showed neddylation stabilizes EphB1 and enhances kinase activity to promote hepatic stellate cell activation.

    Evidence Neddylation IP, kinase activity assay, proliferation and migration assays

    PMID:36834826

    Open questions at the time
    • Neddylation site and responsible ligase not mapped
  21. 2023 Medium

    Systematically parsed cancer-mutation effects, linking reduced-compartmentalization mutants to altered PI3K-pathway phosphorylation.

    Evidence Confocal compartmentalization assay and phosphoproteomics across 15 mutants in CRC cells

    PMID:38102712

    Open questions at the time
    • Causal role of PIK3C2B phosphorylation in compartmentalization not tested
  22. 2024 High

    Pinpointed the cell-autonomous requirement for EphB1 in GABAergic neurons for long-range cortical glutamatergic axon guidance.

    Evidence Cell-type-specific conditional knockout (Vgat-Cre, Emx1-Cre, Tie2-Cre), axon tracing, IHC

    PMID:38345254

    Open questions at the time
    • Molecular signal between GABAergic EphB1 and glutamatergic axons not defined
  23. 2024 Medium

    Revealed a tumor-platelet axis in which tumor EPHB1 activates platelets via ephrin-B1 reverse signaling to release pro-tumor serotonin.

    Evidence Ephb1 GOF/LOF, tumor-platelet adhesion assay, recombinant proteins, Tph1-knockout mice, niche labeling

    PMID:39648610

    Open questions at the time
    • Generalizability beyond pancreatic liver-metastatic niche untested
  24. 2025 Medium

    Defined dual molecular mechanisms—NR2B Tyr1472 phosphorylation and KCC2 degradation—by which EphB1 drives thalamocortical excitation and anesthesia emergence.

    Evidence Conditional KO, in vivo electrophysiology, NR2B phosphorylation and KCC2 ubiquitination assays, chemo/optogenetics

    PMID:41348875

    Open questions at the time
    • Relative contribution of the two mechanisms in vivo not quantified
  25. 2025 Medium

    Linked EphB1 to hypothalamic energy homeostasis via cell-autonomous PI3K/AKT/CREB control of CRH/TRH and thermogenesis.

    Evidence Forward genetic screen, PI3K/AKT inhibitors, ICV peptide rescue, metabolic phenotyping

    PMID:40207393

    Open questions at the time
    • Whether the phenotype requires ligand engagement or kinase activity unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How EphB1's many context-dependent outputs—forward vs reverse signaling, kinase-dependent tumor suppression vs ligand-independent EMT promotion, and tissue-specific effector selection—are integrated at a structural and regulatory level remains unresolved.
  • No unified model linking post-translational modifications (Cbl, SUMO, neddylation) to effector choice
  • Determinants of receptor specificity over other EphB receptors in vivo undefined
  • Structural basis of compartmentalization versus signaling outputs unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 5 GO:0016740 transferase activity 3 GO:0060089 molecular transducer activity 3 GO:0060090 molecular adaptor activity 2
Localization
GO:0005886 plasma membrane 2 GO:0031410 cytoplasmic vesicle 2
Pathway
R-HSA-1266738 Developmental Biology 4 R-HSA-162582 Signal Transduction 3 R-HSA-1643685 Disease 3 R-HSA-112316 Neuronal System 2
Partners
CAV1CBLEFNB1EFNB2GRB7NCK1SHC1SRC
Complex memberships
caveolae

Evidence

Reading pass · 33 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 EphB1 functions as a 'ligand density sensor': engagement with ephrin-B1 at high surface density activates integrin-mediated cell attachment (alphavbeta3 in endothelial cells; alpha5beta1 in transfected HEK cells) without mechanical tethering. Activation-competent but signaling-defective EphB1 point mutants failed to stimulate ephrin-B1-dependent attachment, demonstrating requirement for EphB1 kinase signaling. Reconstituted ephrin-B1 surface density assay, integrin-blocking antibodies, EphB1 point mutants in transfection experiments, cell attachment assays The EMBO journal High 10205170
1998 The adapter protein Nck binds directly to the juxtamembrane region of EphB1 via its SH2 domain, requiring phospho-Tyr594. Ligand (ephrin-B1/Fc) activation of EphB1 recruits Nck to native receptor complexes and activates c-Jun kinase (JNK/SAPK). Mutant EphB1-Y594F blocks Nck recruitment, attenuates JNK activation, and blocks cell attachment responses. Yeast two-hybrid cloning, Co-immunoprecipitation, site-directed mutagenesis (Y594F), JNK kinase assay, cell attachment assay The Journal of biological chemistry High 9430661
2003 Activated EphB1 recruits adaptor proteins Grb2 and p52Shc, promotes c-Src-dependent tyrosine phosphorylation of p52Shc, and activates MAPK/ERK to drive cell chemotaxis. EphB1 Tyr600 and Tyr778 are required for interaction with c-Src and p52Shc. Phosphorylation of p52Shc by c-Src is required for its recruitment to EphB1 complexes via its phosphotyrosine binding domain. ERK and Src inhibitors abolished EphB1-mediated migration but not adhesion. Co-immunoprecipitation, site-directed mutagenesis (Y600F, Y778F), dominant-negative c-Src expression, pharmacological inhibitors (PD98059, PP2), cell migration and adhesion assays The Journal of cell biology High 12925710
2002 Grb7 binds to the cytoplasmic domain of EphB1 via its SH2 domain in a manner requiring EphB1 autophosphorylation. Tyr-928 of EphB1 is the primary Grb7 binding site. EphB1 can phosphorylate Grb7, and mutations Y928F or Y594F reduced this activity. Co-expression of Grb7 with EphB1 enhanced cell motility, while the Grb7 SH2 domain alone abolished EphB1-stimulated migration. Yeast two-hybrid screening, Co-immunoprecipitation, site-directed mutagenesis, kinase assay, cell migration assay on extracellular matrix The Journal of biological chemistry High 12223469
2001 The kinase-inactive EphB6 receptor undergoes transphosphorylation upon ligand (ephrin-B1) stimulation when co-expressed with catalytically active EphB1. EphB1 and EphB6 form a stable hetero-complex; EphB1-induced EphB6 phosphorylation requires EphB1 catalytic activity. The proto-oncogene c-Cbl was identified as a constitutive EphB6-binding protein requiring a functional phosphotyrosine binding domain. Co-immunoprecipitation, overexpression of kinase-dead EphB1 mutants, ligand stimulation assays The Journal of biological chemistry Medium 11713248
2004 Activated EphB1 induces c-Src-dependent tyrosine phosphorylation of paxillin at Tyr-31 and Tyr-118, and is recruited to paxillin-FAK complexes. Cells expressing paxillin Y31F/Y118F or paxillin ΔLD4 show reduced EphB1-dependent migration. Nck binding site mutation (Y594F) disrupts the Nck-paxillin-EphB1 complex, establishing a signaling complex: EphB1 → Nck → paxillin/FAK → c-Src-mediated paxillin phosphorylation → cell migration. Co-immunoprecipitation, site-directed mutagenesis (paxillin Y31F/Y118F, EphB1 Y594F), dominant-negative c-Src, Src inhibitor PP2, cell migration assay The Journal of biological chemistry High 15107421
2006 EphB1 receptors localize to caveolae and directly interact with caveolin-1 (Cav-1) upon ligand stimulation. This interaction requires the caveolin-binding motif within the EphB1 kinase domain, which is also required for correct membrane targeting of EphB1. Overexpression of a Cav-1 mutant lacking the scaffolding domain abolishes EphB1-Cav-1 interaction and EphB1-mediated ERK activation. Subcellular fractionation, co-immunoprecipitation, caveolin-1 scaffolding domain mutant overexpression, confocal microscopy, ERK activation assays Journal of cell science Medium 16723736
2007 Ligand (ephrin-B1) stimulation of EphB1 leads to Cbl recruitment to EphB1 via Cbl's tyrosine kinase-binding domain, followed by Src-dependent Cbl phosphorylation, EphB1 ubiquitination, and lysosomal degradation of EphB1. Overexpression of wild-type but not the ligase-dead 70Z Cbl mutant enhanced EphB1 ubiquitination and degradation. Kinase-dead EphB1-K652R was resistant to Cbl-mediated degradation. Co-immunoprecipitation, GST pull-down, overexpression of Cbl mutants, ubiquitination assay, lysosomal inhibitor (bafilomycin) treatment, Src inhibitor (PP2) Traffic (Copenhagen, Denmark) High 18034775
2003 Ephrin-B2 is expressed at the optic chiasm midline and selectively repels ventrotemporal retinal ganglion cell (RGC) axons that express EphB1. EphB1 is found exclusively in retinal regions giving rise to the ipsilateral projection. EphB1 null mice exhibit a dramatically reduced ipsilateral retinal projection, and blocking ephrin-B2 function in vitro eliminates the inhibitory effect on chiasm cells and abolishes ipsilateral projection in semiintact preparation. Immunohistochemistry, EphB1 knockout mouse, in vitro axon growth assays with function-blocking reagents, semiintact visual system preparation Neuron High 12971893
1997 EphB1 (and EphA4) expressed in migrating third arch neural crest cells interact with ephrin-B2 in second arch neural crest/mesoderm to restrict intermingling and direct targeted migration. Inhibition of EphB1/EphA4 function using truncated receptors leads to abnormal third arch neural crest migration into second and fourth arch territories; ectopic ephrin-B2 overexpression scatters third arch cells. Dominant-negative truncated receptor expression in Xenopus embryos, ectopic ephrin-B2 overexpression, in situ hybridization, cell lineage tracing Current biology : CB Medium 9259557
1999 EphB1 and its ligand ephrin-B2 are expressed in complementary patterns in midbrain dopaminergic neurons and their targets. Ephrin-B2 selectively inhibits neurite outgrowth and induces cell loss of substantia nigra (but not ventral tegmental) dopaminergic neurons, suggesting EphB1/ephrin-B2 specifies distinct dopaminergic pathways. Ephrin-B2 expression is upregulated by cocaine and amphetamine in adults. Neurite outgrowth inhibition assay, cell survival assay, in situ hybridization, immunohistochemistry The Journal of neuroscience Medium 10066262
2008 Zic2 transcription factor regulates EphB1 expression in retinal ganglion cells. Ectopic delivery of Zic2 into non-VT retinal explants induces EphB1 mRNA and protein expression. The upregulated EphB1 localizes to growth cones and is functional, converting RGC axon behavior from extension onto to avoidance of ephrin-B2 substrates, demonstrating Zic2→EphB1 axis controls ipsilateral projection. Retinal explant electroporation, in vitro axon growth/avoidance assays on ephrin-B2 substrates, immunofluorescence for EphB1 protein in growth cones The Journal of neuroscience High 18524895
2009 EphB1 is specifically required and sufficient to drive the ipsilateral retinal projection. In utero retinal electroporation of EphB1 redirects normally-crossed RGCs to ipsilateral trajectory. EphB2, despite high similarity, is far less efficient. EphB1-EphB2 chimeric receptor analysis reveals that both extracellular and juxtamembrane domains of EphB1 are specifically required for ipsilateral redirection. In utero retinal electroporation, chimeric receptor expression, in vivo axon tracing The Journal of neuroscience High 19295152
2011 EphB1 forward signaling (into the EphB1-expressing cell) is specifically required for ipsilateral retinal axon projection; reverse signaling through the EphB1 extracellular domain is not required. Knock-in mice expressing intracellular-truncated EphB1 (EphB1T-lacZ) fail to form the ipsilateral projection, phenocopying the EphB1 null. EphB1 is the preferred receptor for ephrin-B2 (and less so ephrin-B1) at the optic chiasm. Knock-in mouse (intracellular truncation), retinal axon tracing, genetic analysis of EphB/ephrin-B mutant combinations The European journal of neuroscience High 22103419
2008 EphB1 null mice show a 40% decrease in neuron number and volume in substantia nigra pars reticulata (SNr), but not in pars compacta TH+ neurons. EphB1 is expressed in SNr (not SNc) neurons. Loss of EphB1 results in spontaneous locomotor hyperactivity, linking EphB1-dependent SNr development to locomotor function. EphB1 knockout mice, stereological neuron counting, in situ hybridization, beta-galactosidase reporter, open-field behavioral testing The European journal of neuroscience Medium 17561836
2012 EphB1 recruits scaffold protein Caskin1 via the adaptor Nck: EphB1 activation leads to Nck SH2 binding to phosphotyrosine on EphB1, while Nck SH3 domains interact with the proline-rich domain of Caskin1. This complex formation results in tyrosine phosphorylation of Caskin1 at Tyr296 and Tyr336 (identified by mass spectrometry), and phosphorylation causes structural changes in the Caskin1 SH3 domain detected by CD spectroscopy. Co-immunoprecipitation, mass spectrometry phosphosite identification, CD spectroscopy Cell communication and signaling : CCS Medium 23181695
2012 PTEN is constitutively associated with c-Cbl, protecting Cbl from degradation. EphB1 stimulation triggers PTEN dephosphorylation (~50% on Ser/Thr) and disruption of the PTEN-Cbl complex, requiring PTEN protein phosphatase activity. Both PTEN and Cbl independently translocate to EphB1, with PTEN associating via scaffold protein NHERF1. PTEN lipid phosphatase activity impairs EphB1-dependent cell adhesion and chemotaxis. Co-immunoprecipitation, PTEN and NHERF1 siRNA knockdown, PTEN phosphatase mutants, cell adhesion and chemotaxis assays FASEB journal Medium 23118026
2017 EphB1 is upregulated in injured motor neurons and can activate astrocytes through ephrin-B1-mediated stimulation of STAT3. EphB1-induced astrocyte activation produces a protective and anti-inflammatory transcriptional signature distinct from IL-6-induced responses. This EphB1-ephrin-B1-STAT3 pathway is disrupted in human stem cell-derived astrocytes and mouse models of ALS. Transcriptional analysis of EphB1-stimulated astrocytes, STAT3 pathway analysis, human iPSC-derived astrocytes, ALS mouse models Nature communications Medium 29079839
2018 The RhoGAP protein Porf-2 is an intracellular mediator of EphB1 signaling in axon growth inhibition. EphB1 binds and regulates Porf-2 upon ephrin-B stimulation. The activated EphB1 forward signal deactivates Rac1 through the GAP domain of Porf-2, which inhibits growth cone expansion and brakes axon outgrowth. Co-immunoprecipitation of EphB1-Porf-2, Rac1 activity assays (GTP-Rac1 pull-down), axon growth measurement, GAP domain mutagenesis Cellular and molecular life sciences : CMLS Medium 29938386
2020 EphB1 constitutively interacts with caveolin-1 (Cav-1) in endothelial cells. Ephrin-B1 activation of EphB1 induces EphB1 phosphorylation, uncouples EphB1 from Cav-1, and promotes Src-dependent Cav-1 phosphorylation. Deletion of the CSD-binding motif in EphB1 prevents Cav-1 interaction and Cav-1 phosphorylation. EphB1-/- ECs show markedly reduced Cav-1 expression and caveolae numbers due to Cav-1 ubiquitination and degradation when not bound to EphB1. Super-resolution microscopy, FRET, co-immunoprecipitation, EphB1 CSD-motif deletion mutant, EphB1 knockout endothelial cells, electron microscopy caveolae counting Molecular biology of the cell High 32238105
2021 Tetracycline antibiotics demeclocycline, chlortetracycline, and minocycline inhibit EphB1 kinase activity at low micromolar concentrations by binding to the ATP-binding catalytic domain. Co-crystallization of chlortetracycline with EphB1 confirmed binding to the ATP-binding domain. In vivo, the three-tetracycline combination inhibited EphB1 phosphorylation in brain, spinal cord, and DRG and blocked neuropathic pain in mice. In silico docking screen, in vitro kinase assay, X-ray co-crystallography (chlortetracycline-EphB1), in vivo phosphorylation assay, neuropathic pain behavioral model Proceedings of the National Academy of Sciences of the United States of America High 33627480
2014 EphB1 expressed in the striatal anlage signals to ephrin-B3 on migrating cortical interneurons and striatal neurons via reverse signaling with opposite effects: in cortical interneurons, EphB1-ephrin-B3 reverse signaling phosphorylates Src and FAK causing repulsion; in striatal neurons expressing ephrin-B3, EphB1 reduces pSrc and pFAK causing cessation of migration. In ephrin-B3 knockout mice, cortical interneurons are misrouted into the striatum and striatal neurons over-migrate. In vitro migration assays, ephrin-B3 knockout mouse, immunofluorescence for pSrc/pFAK, in vivo cell tracking Frontiers in cellular neuroscience Medium 25100946
2015 EphB1 intracellular signaling domains are required for corpus callosum and anterior commissure formation. Truncated EphB1/EphB2 mice lacking intracellular domains show partial/complete agenesis of corpus callosum and highly penetrant anterior commissure misprojection, indicating forward (and potentially reverse) intracellular signaling by EphB1/EphB2 is required for forebrain axon guidance. Knock-in truncated EphB1/EphB2 mice, axon tract tracing, immunohistochemistry Developmental neurobiology Medium 26148571
2015 EphB1 ligand-dependent signaling activates the DNA damage response (DDR) cascade via p53 DNA binding, leading to activation of ATR, Chk1, p53, p21, p38, CDK1(Tyr15) and Bax, and downregulation of HSP27 and Bcl2. In EphB1-methylated AML cells, re-introduction of EphB1 enhanced the DDR cascade and enforced programmed cell death, identifying EphB1 as a tumor suppressor in AML. EphB1 re-expression in methylated AML cells, signaling pathway analysis by western blot, promoter methylation analysis, p53 DNA binding assay Molecular cancer research : MCR Medium 25944917
2023 Neddylation of EphB1 enhances its kinase activity by preventing its degradation, thereby promoting proliferation, migration, and activation of hepatic stellate cells. EphB1 expression and neddylation are both increased in activated hepatic stellate cells. Neddylation assay (immunoprecipitation), kinase activity assay, hepatic stellate cell functional assays (proliferation, migration) International journal of molecular sciences Medium 36834826
2023 CRC-associated somatic mutations in EphB1 reduce kinase activity and protein stability. CRC mutant EphB1 receptors inhibit STAT3 and ERK1/2 signaling (contrasting wild-type) and are unable to suppress migration of CRC cells or compartmentalize cells in ephrin-B1 co-culture assays, establishing a kinase-dependent tumor suppressor function. Purified recombinant WT and mutant EphB1 kinase domain assays, cell migration assay, cell compartmentalization assay, mammalian cell expression The Journal of biological chemistry High 37527777
2018 SUMOylation of EphB1 at lysine residue 785 suppresses cell proliferation, anchorage-independent growth, and xenograft tumor growth. SUMOylated EphB1 represses activation of its downstream effector PKCγ. A reciprocal regulatory loop between PKCγ and EphB1 SUMOylation was identified. Ni2+-NTA pull-down and immunoprecipitation for SUMOylation, K785R mutant expression, soft agar colony formation, xenograft mouse model, PKCγ activation assay Cellular physiology and biochemistry Medium 29550816
2024 Tumor cell-expressed EPHB1 interacts with platelet-expressed EFNB1 (ephrin-B1) in the liver metastatic niche of pancreatic ductal adenocarcinoma. This contact-dependent EPHB1-EFNB1 interaction activates platelets via reverse signaling through AKT signaling; activated platelets then release serotonin (5-HT) which promotes tumor growth. Gain-of-function and loss-of-function of Ephb1, tumor cell-platelet adhesion assay, recombinant protein treatments, Tph1-knockout mice (serotonin-deficient), mCherry niche-labeling system Cancer communications (London, England) Medium 39648610
2024 EphB1 in GABAergic neurons (not cortical excitatory neurons or endothelial cells) is required for proper long-range cortical glutamatergic axon guidance. Conditional EphB1 knockout in GABAergic cells (Vgat-Cre) reproduces the cortical axon guidance defects of global EphB1 KO, with misguided axon bundles containing co-mingled GABAergic and glutamatergic axons near blood vessels. Cell-type-specific conditional knockout (Vgat-Cre, Emx1-Cre, Tie2-Cre), axon tract tracing, immunohistochemistry Development (Cambridge, England) High 38345254
2025 EphB1 in glutamatergic neurons of the ventral posteromedial thalamic nucleus (VPM) promotes emergence from anesthesia by activating the VPMGlu→primary somatosensory cortex pathway. EphrinB-EphB1 signaling excites VPMGlu neurons through NR2B phosphorylation at Tyr-1472, and disinhibits VPMGlu neurons through ubiquitin-mediated degradation of KCC2; these are identified as two independent mechanisms. Conditional knockout, in vivo electrophysiology, NR2B phosphorylation assays, KCC2 ubiquitination assay, chemogenetics/optogenetics to probe neural circuit Science advances Medium 41348875
2020 TGF-β-activated Smad2 transcriptionally upregulates endogenous EphB1 expression in lung cancer cells. Ligand-independent (unphosphorylated) EphB1 promotes epithelial-mesenchymal transition (EMT) by upregulating CDH2 (N-cadherin) and increases migration and invasion, while ligand-dependent (phosphorylated) EphB1 (activated by ephrin-B2) inhibits migration and invasion. EphB1 phosphorylation mutant expression, western blot for Smad2 and CDH2, transwell migration/invasion assay, siRNA knockdown Journal of Cancer Medium 32368295
2025 EphB1 promotes CREB phosphorylation via PI3K/AKT signaling in a cell-autonomous manner in hypothalamic neurons. EphB1 deficiency reduces hypothalamic CRH and TRH expression, leading to impaired thermogenesis and locomotion (but not food intake), and results in obesity. Intraventricular administration of TRH or CRH suppressed obesity in Ephb1 mutant mice. Forward genetic screen, hypothalamic tissue and primary cell signaling analysis, PI3K/AKT pathway inhibitors, intracerebroventricular peptide delivery, metabolic phenotyping Obesity (Silver Spring, Md.) Medium 40207393
2023 Recurring EPHB1 mutations in colorectal and other cancers alter receptor signaling and cell compartmentalization. Ligand-binding domain mutations (C61Y, R90C, R170W), fibronectin domain mutation (R351L), and kinase domain mutation (D762N) reduce compartmentalization and ligand-induced receptor phosphorylation. Kinase domain mutations R743W and G821R enhance compartmentalization without altered phosphorylation. Phosphoproteome analysis linked reduced-compartmentalization mutants to PI3K pathway/PIK3C2B phosphorylation. Confocal microscopy compartmentalization assay, phospho-proteome analysis, stable expression of 15 mutants in CRC cells Cell communication and signaling : CCS Medium 38102712

Source papers

Stage 0 corpus · 64 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1997 The EphA4 and EphB1 receptor tyrosine kinases and ephrin-B2 ligand regulate targeted migration of branchial neural crest cells. Current biology : CB 282 9259557
2003 Ephrin-B2 and EphB1 mediate retinal axon divergence at the optic chiasm. Neuron 265 12971893
2002 Subtractive hybridization reveals the expression of immunoglobulin-like transcript 7, Eph-B1, granzyme B, and 3 novel transcripts in human plasmacytoid dendritic cells. Blood 194 12384430
1999 Surface densities of ephrin-B1 determine EphB1-coupled activation of cell attachment through alphavbeta3 and alpha5beta1 integrins. The EMBO journal 178 10205170
1998 Nck recruitment to Eph receptor, EphB1/ELK, couples ligand activation to c-Jun kinase. The Journal of biological chemistry 139 9430661
1999 Specification of distinct dopaminergic neural pathways: roles of the Eph family receptor EphB1 and ligand ephrin-B2. The Journal of neuroscience : the official journal of the Society for Neuroscience 107 10066262
2017 A neuroprotective astrocyte state is induced by neuronal signal EphB1 but fails in ALS models. Nature communications 102 29079839
2011 Blocking EphB1 receptor forward signaling in spinal cord relieves bone cancer pain and rescues analgesic effect of morphine treatment in rodents. Cancer research 91 21555368
2003 EphB1 recruits c-Src and p52Shc to activate MAPK/ERK and promote chemotaxis. The Journal of cell biology 91 12925710
2008 Zic2 promotes axonal divergence at the optic chiasm midline by EphB1-dependent and -independent mechanisms. Development (Cambridge, England) 89 18417618
2001 The kinase-null EphB6 receptor undergoes transphosphorylation in a complex with EphB1. The Journal of biological chemistry 83 11713248
2002 EphB1 associates with Grb7 and regulates cell migration. The Journal of biological chemistry 76 12223469
2010 Resequencing and association analysis of the KALRN and EPHB1 genes and their contribution to schizophrenia susceptibility. Schizophrenia bulletin 70 21041834
2008 Zic2 regulates retinal ganglion cell axon avoidance of ephrinB2 through inducing expression of the guidance receptor EphB1. The Journal of neuroscience : the official journal of the Society for Neuroscience 58 18524895
2004 EphB1-mediated cell migration requires the phosphorylation of paxillin at Tyr-31/Tyr-118. The Journal of biological chemistry 58 15107421
2009 Specificity and sufficiency of EphB1 in driving the ipsilateral retinal projection. The Journal of neuroscience : the official journal of the Society for Neuroscience 56 19295152
2007 Involvement of EphB1 receptor/EphrinB2 ligand in neuropathic pain. Spine 52 17621205
2006 Caveolin-1 is required for signaling and membrane targeting of EphB1 receptor tyrosine kinase. Journal of cell science 47 16723736
2008 Targeted mutation of EphB1 receptor prevents development of neuropathic hyperalgesia and physical dependence on morphine in mice. Molecular pain 40 19025592
2011 Involvement of EphB1 receptor/ephrinB1 ligand in bone cancer pain. Neuroscience letters 39 21514363
2009 An in vivo mouse model of long-term potentiation at synapses between primary afferent C-fibers and spinal dorsal horn neurons: essential role of EphB1 receptor. Molecular pain 39 19523204
2007 Proangiogenic role of ephrinB1/EphB1 in basic fibroblast growth factor-induced corneal angiogenesis. The American journal of pathology 35 17255342
2013 Involvement of EphB1 receptors signalling in models of inflammatory and neuropathic pain. PloS one 34 23341972
2007 Ligand binding induces Cbl-dependent EphB1 receptor degradation through the lysosomal pathway. Traffic (Copenhagen, Denmark) 33 18034775
2013 Ligand-dependent EphB1 signaling suppresses glioma invasion and correlates with patient survival. Neuro-oncology 30 24121831
2011 Forward signaling by EphB1/EphB2 interacting with ephrin-B ligands at the optic chiasm is required to form the ipsilateral projection. The European journal of neuroscience 30 22103419
2007 EphB1 null mice exhibit neuronal loss in substantia nigra pars reticulata and spontaneous locomotor hyperactivity. The European journal of neuroscience 29 17561836
2008 EphB1 is underexpressed in poorly differentiated colorectal cancers. Pathobiology : journal of immunopathology, molecular and cellular biology 28 18931529
2015 Knockdown of EphB1 receptor decreases medulloblastoma cell growth and migration and increases cellular radiosensitization. Oncotarget 27 25879388
1995 cDNA cloning, molecular characterization, and chromosomal localization of NET(EPHT2), a human EPH-related receptor protein-tyrosine kinase gene preferentially expressed in brain. Genomics 26 8666391
2008 Loss of expression of EphB1 protein in gastric carcinoma associated with invasion and metastasis. Oncology 23 18424888
2000 Regulation of EphB1 expression by dopamine signaling. Brain research. Molecular brain research 23 11146119
2021 Identification of tetracycline combinations as EphB1 tyrosine kinase inhibitors for treatment of neuropathic pain. Proceedings of the National Academy of Sciences of the United States of America 22 33627480
2020 Ligand-independent EphB1 signaling mediates TGF-β-activated CDH2 and promotes lung cancer cell invasion and migration. Journal of Cancer 22 32368295
2014 Increased expression of P2RY2, CD248 and EphB1 in gastric cancers from Chilean patients. Asian Pacific journal of cancer prevention : APJCP 22 24716914
2017 Paradoxes of the EphB1 receptor in malignant brain tumors. Cancer cell international 20 28194092
2012 Complex formation of EphB1/Nck/Caskin1 leads to tyrosine phosphorylation and structural changes of the Caskin1 SH3 domain. Cell communication and signaling : CCS 19 23181695
2015 EphB1 Suppression in Acute Myelogenous Leukemia: Regulating the DNA Damage Control System. Molecular cancer research : MCR 18 25944917
2014 A dual role of EphB1/ephrin-B3 reverse signaling on migrating striatal and cortical neurons originating in the preoptic area: should I stay or go away? Frontiers in cellular neuroscience 18 25100946
2015 EphB1 and EphB2 intracellular domains regulate the formation of the corpus callosum and anterior commissure. Developmental neurobiology 16 26148571
2022 Cell-cell contact-driven EphB1 cis- and trans- signalings regulate cancer stem cells enrichment after chemotherapy. Cell death & disease 14 36402751
2005 Nurr1 co-localizes with EphB1 receptors in the developing ventral midbrain, and its expression is enhanced by the EphB1 ligand, ephrinB2. Journal of neurochemistry 14 15663472
2023 Neddylation of EphB1 Regulates Its Activity and Associates with Liver Fibrosis. International journal of molecular sciences 13 36834826
2020 EphB1 interaction with caveolin-1 in endothelial cells modulates caveolae biogenesis. Molecular biology of the cell 11 32238105
2013 Tissue-specific venous expression of the EPH family receptor EphB1 in the skin vasculature. Developmental dynamics : an official publication of the American Association of Anatomists 11 23649798
2020 Peripheral EphrinB1/EphB1 signalling attenuates muscle hyperalgesia in MPS patients and a rat model of taut band-associated persistent muscle pain. Molecular pain 10 33356837
2018 Neuronal GAP-Porf-2 transduces EphB1 signaling to brake axon growth. Cellular and molecular life sciences : CMLS 10 29938386
2021 Genetic variants of DOCK2, EPHB1 and VAV2 in the natural killer cell-related pathway are associated with non-small cell lung cancer survival. American journal of cancer research 9 34094683
2023 Colorectal cancer-associated mutations impair EphB1 kinase function. The Journal of biological chemistry 7 37527777
2018 Analgesic effects of microRNA-129-5p against bone cancer pain through the EphB1/EphrinB2 signaling pathway in mice. Journal of cellular biochemistry 6 29236320
2023 EphB1 promotes the differentiation and maturation of dendritic cells in non-small cell lung cancer. Cancer letters 5 38070822
2014 Decreased expression of receptor tyrosine kinase of EphB1 protein in renal cell carcinomas. International journal of clinical and experimental pathology 5 25120806
2012 Phosphatase and tensin homolog regulates stability and activity of EphB1 receptor. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 5 23118026
2024 EphB1 controls long-range cortical axon guidance through a cell non-autonomous role in GABAergic cells. Development (Cambridge, England) 4 38345254
2024 Reciprocal tumor-platelet interaction through the EPHB1-EFNB1 axis in the liver metastatic niche promotes metastatic tumor outgrowth in pancreatic ductal adenocarcinoma. Cancer communications (London, England) 4 39648610
2014 EphB1 and Ephrin-B, new potential biomarkers for squamous cell/adenosquamous carcinomas and adenocarcinomas of the gallbladder. Asian Pacific journal of cancer prevention : APJCP 4 24606480
2011 Associations of EPHB1 polymorphisms with hepatocellular carcinoma in the Korean population. Human immunology 4 21763378
2023 The combination of tetracyclines effectively ameliorates liver fibrosis via inhibition of EphB1/2. International immunopharmacology 2 37992441
2023 Recurring EPHB1 mutations in human cancers alter receptor signalling and compartmentalisation of colorectal cancer cells. Cell communication and signaling : CCS 2 38102712
2018 Sumoylation of EphB1 Suppresses Neuroblastoma Tumorigenesis via Inhibiting PKCγ Activation. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 2 29550816
2024 EphB1 causes retinal damage through inflammatory pathways in the retina and retinal Müller cells. Molecular vision 1 38601015
2025 Disruption of Ephb1 causes reduced hypothalamic CRH and TRH expression and obesity in mice. Obesity (Silver Spring, Md.) 0 40207393
2025 EPHB1 Protein Promoted the Progression of Prostate Adenocarcinoma Through Phosphorylating GSK3B and Activating EPHB1-GSK3B-SMAD3 Pathway. Human mutation 0 40548257
2025 EphB1-NR2B receptor signaling in glutamatergic neurons of the ventroposteromedial thalamic nucleus regulates emergence from anesthesia. Science advances 0 41348875

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