Affinage

EPHB1

Ephrin type-B receptor 1 · UniProt P54762

Length
984 aa
Mass
109.9 kDa
Annotated
2026-04-28
64 papers in source corpus 34 papers cited in narrative 34 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

EphB1 is a receptor tyrosine kinase that transduces ephrin-B ligand engagement into diverse cellular outcomes—including repulsive axon guidance, integrin-mediated cell adhesion, directed cell migration, and synaptic plasticity—through multiple phosphotyrosine-dependent signaling branches. Ligand-stimulated EphB1 autophosphorylation recruits Nck (via pY594) to activate JNK and paxillin phosphorylation, c-Src/Shc (via pY600/pY778) to drive MAPK/ERK-dependent chemotaxis, and Grb7 (via pY928) to promote cell motility; it also signals through PI3K/AKT/CREB in hypothalamic neurons and phosphorylates NMDA receptor NR2B subunits in spinal and thalamic circuits to modulate pain sensitization and arousal (PMID:9430661, PMID:12925710, PMID:12223469, PMID:40207393, PMID:41348875). EphB1 is the primary receptor mediating ephrin-B2–dependent repulsion of ventrotemporal retinal ganglion cell axons at the optic chiasm, and its forward signaling is required for ipsilateral retinal projection, corpus callosum formation, and cortical axon guidance via a non-cell-autonomous mechanism in GABAergic neurons (PMID:12971893, PMID:22103419, PMID:26148571, PMID:38345254). EphB1 activity is regulated by caveolin-1–dependent membrane compartmentalization, Cbl-mediated ubiquitination and lysosomal degradation, SUMOylation at K785 that represses PKCγ, and neddylation that stabilizes the receptor and enhances kinase output (PMID:32238105, PMID:18034775, PMID:29550816, PMID:36834826).

Mechanistic history

Synthesis pass · year-by-year structured walk · 20 steps
  1. 1997 High

    Establishing EphB1 as a guidance receptor: the first demonstration that EphB1 mediates repulsive boundary formation during neural crest migration via ephrin-B2 interaction, answering how branchial arch territories are maintained.

    Evidence Dominant-negative truncated EphB1 overexpression in Xenopus embryos caused neural crest mis-migration into adjacent arch territories

    PMID:9259557

    Open questions at the time
    • Downstream signaling pathways mediating repulsion were unknown
    • Mammalian relevance not tested
  2. 1998 High

    Identifying the first signaling branch downstream of EphB1: Nck adaptor binds pY594 in the juxtamembrane region and couples the receptor to JNK/SAPK activation and cell attachment, establishing the first defined phosphotyrosine-effector link.

    Evidence Yeast two-hybrid, co-IP, Y594F mutagenesis, and JNK kinase assay

    PMID:9430661

    Open questions at the time
    • Other signaling branches (MAPK/ERK) not yet mapped
    • In vivo relevance of Nck–JNK axis not tested
  3. 1999 High

    Demonstrating that EphB1 acts as a ligand-density sensor to regulate integrin-mediated adhesion, establishing that the kinase's signaling output—not mechanical tethering—controls cell attachment through αvβ3 and α5β1 integrins.

    Evidence Reconstituted ephrin-B1 surface density assay with signaling-dead EphB1 point mutants and integrin-blocking antibodies

    PMID:10205170

    Open questions at the time
    • Which specific signaling branch connects to integrin activation was unclear
    • Density-sensing mechanism at receptor level not resolved
  4. 2002 High

    Mapping the Grb7–pY928 signaling branch: EphB1 phosphorylates Grb7 via its SH2 domain binding to pY928, and this interaction drives cell motility, revealing a third distinct phosphotyrosine-dependent output.

    Evidence Yeast two-hybrid, co-IP, Y928F mutagenesis, dominant-negative Grb7 SH2 domain, cell migration assay

    PMID:12223469

    Open questions at the time
    • Relationship between Grb7 and integrin-mediated outputs not clarified
    • In vivo relevance not tested
  5. 2003 High

    Defining EphB1 as the essential receptor for ipsilateral retinal axon guidance at the optic chiasm: EphB1 knockout mice lose most ipsilateral projection, and ephrin-B2 at the midline selectively repels EphB1-expressing ventrotemporal RGC axons.

    Evidence EphB1 knockout mouse with anterograde tracing, stripe/collapse assays, blocking antibodies

    PMID:12971893

    Open questions at the time
    • Forward vs. reverse signaling contribution not yet dissected
    • Downstream intracellular effectors mediating growth cone turning uncharacterized
  6. 2003 High

    Mapping the c-Src/Shc–MAPK/ERK chemotaxis branch: pY600 and pY778 recruit c-Src and p52Shc; Src-dependent Shc phosphorylation activates ERK to drive directional migration, providing a second major signaling axis for cell motility.

    Evidence Co-IP, Y600F/Y778F mutagenesis, Src inhibitor PP2, MEK inhibitor PD98059, cell migration assay

    PMID:12925710

    Open questions at the time
    • Cross-talk between Nck–JNK and Src–ERK branches not defined
    • Relative contribution of branches to in vivo guidance unknown
  7. 2004 High

    Linking EphB1 signaling to focal adhesion remodeling: activated EphB1 drives Src-dependent paxillin phosphorylation at Y31/Y118 and assembles an EphB1–Nck–paxillin–FAK complex required for migration.

    Evidence Co-IP, paxillin Y31F/Y118F and EphB1 Y594F mutagenesis, kinase-dead Src, migration assay

    PMID:15107421

    Open questions at the time
    • How paxillin phosphorylation coordinates with integrin activation from the 1999 study was unknown
    • Spatial dynamics of complex assembly not resolved
  8. 2006 Medium

    Establishing caveolae as a signaling platform for EphB1: the receptor localizes to caveolae via a caveolin-binding motif in the kinase domain, and this compartmentalization is required for ERK activation.

    Evidence Sucrose gradient fractionation, co-IP, dominant-negative caveolin-1 lacking scaffolding domain

    PMID:16723736

    Open questions at the time
    • Stoichiometry of EphB1–caveolin-1 interaction not determined
    • Whether caveolar localization affects other signaling branches (JNK, Grb7) unknown
  9. 2007 High

    Defining the degradation pathway: Cbl is recruited to activated EphB1 in a Src-dependent manner, ubiquitinates the receptor, and targets it for lysosomal degradation, establishing how EphB1 signaling is attenuated.

    Evidence Ubiquitination assay, bafilomycin inhibition, GST pull-down of Cbl TKB domain, kinase-dead K652R mutant resistant to degradation, PP2 Src inhibitor

    PMID:18034775

    Open questions at the time
    • Specific ubiquitin chain types (K48 vs. K63) not determined
    • Whether proteasomal degradation also contributes was not resolved
  10. 2008 Medium

    Identifying the transcriptional regulator upstream of EphB1 in retinal neurons: Zic2 drives EphB1 expression and is sufficient to convert RGC axon behavior from extension to avoidance on ephrin-B2 substrates.

    Evidence In utero retinal electroporation, explant growth cone collapse assay

    PMID:18524895

    Open questions at the time
    • Zic2 binding sites in EphB1 regulatory regions not mapped
    • Other transcriptional regulators of EphB1 expression not identified
  11. 2011 High

    Confirming forward signaling as the critical mode at the chiasm: intracellularly truncated EphB1 knock-in eliminates ipsilateral projection, ruling out reverse signaling contributions and proving that the kinase domain and downstream effectors are required.

    Evidence EphB1T-lacZ knock-in mouse with anterograde retinal tracing

    PMID:22103419

    Open questions at the time
    • Which specific intracellular domain (kinase, SAM, PDZ-binding) is essential was not dissected
    • Contribution of kinase activity vs. scaffold function not separated
  12. 2011 Medium

    Extending EphB1 function to pain processing: spinal EphB1 activation by ephrin-B2 phosphorylates NMDA receptor NR1/NR2B subunits to maintain bone cancer pain, with MMP-2/9 regulating EphB1 levels.

    Evidence EphB1 KO mouse, intrathecal EphB2-Fc blocking, immunoblotting for NR subunit phosphorylation, MMP inhibitors

    PMID:21555368

    Open questions at the time
    • Direct phosphorylation vs. indirect Src-mediated NR2B phosphorylation not fully resolved
    • MMP regulation of EphB1 protein levels not mechanistically detailed
  13. 2012 Medium

    Integrating PTEN into the EphB1 signaling network: PTEN constitutively sequesters Cbl, and ephrin stimulation disrupts this complex via PTEN dephosphorylation, freeing both proteins to modulate EphB1 adhesion and migration through NHERF1 scaffold.

    Evidence Co-IP, PTEN/NHERF1 siRNA, phosphatase-dead PTEN mutants, adhesion and migration assays

    PMID:23118026

    Open questions at the time
    • Whether PTEN lipid phosphatase activity directly opposes PI3K signaling downstream of EphB1 was not tested
    • In vivo relevance of PTEN–Cbl regulation not demonstrated
  14. 2018 Medium

    Identifying SUMOylation as a tumor-suppressive post-translational modification of EphB1: K785 SUMOylation represses PKCγ activation and suppresses anchorage-independent growth and xenograft tumor formation.

    Evidence Ni²⁺-NTA pull-down, K785R mutant, xenograft mouse model, soft agar assay, PKCγ activation measurement

    PMID:29550816

    Open questions at the time
    • SUMO E3 ligase responsible not identified
    • Whether SUMOylation and caveolin-1 interaction at the kinase domain are mutually exclusive was not tested
  15. 2020 High

    Resolving the dynamic EphB1–caveolin-1 relationship: EphB1 constitutively protects Cav-1 from ubiquitination; upon ligand activation, phosphorylated EphB1 uncouples from Cav-1 and enables Src-dependent Cav-1 phosphorylation, maintaining caveolae homeostasis in endothelial cells.

    Evidence Super-resolution microscopy, FRET, co-IP, EphB1−/− mouse endothelial cells, Cav-1 ubiquitination assay

    PMID:32238105

    Open questions at the time
    • Whether disrupted caveolae affect vascular permeability in vivo via EphB1 was not addressed
    • Identity of the E3 ligase for Cav-1 in EphB1-null cells unknown
  16. 2023 High

    Characterizing cancer-associated EphB1 mutations: somatic mutations across ligand-binding, fibronectin, and kinase domains reduce kinase activity and protein stability, abolish STAT3/ERK suppression and cell compartmentalization, and activate PIK3C2B through PI3K, establishing EphB1 as a functional tumor suppressor in colorectal cancer.

    Evidence Purified kinase domain assays, thermal stability, migration assay, compartmentalization coculture, phosphoproteomics

    PMID:37527777 PMID:38102712

    Open questions at the time
    • In vivo tumor suppressor role not confirmed by conditional knockout tumor models
    • Whether enhanced-compartmentalization mutations (R743W, G821R) represent gain-of-function or neomorphic activity is unclear
  17. 2023 Medium

    Identifying neddylation as a stabilizing modification: EphB1 neddylation in hepatic stellate cells prevents receptor degradation and sustains kinase activity, promoting HSC proliferation and liver fibrosis.

    Evidence Immunoprecipitation, neddylation inhibitor, kinase activity assay, HSC functional assays

    PMID:36834826

    Open questions at the time
    • Neddylation sites on EphB1 not mapped
    • Interplay between neddylation and Cbl-mediated ubiquitination not tested
  18. 2024 Medium

    Resolving non-cell-autonomous axon guidance: EphB1 in GABAergic (not glutamatergic) neurons provides the guidance signal that prevents glutamatergic cortical axons from aberrantly fasciculating with brain vasculature.

    Evidence Cell-type-specific conditional KO (Vgat-Cre, Emx1-Cre, Tie2-Cre) with anterograde tracing

    PMID:38345254

    Open questions at the time
    • The molecular mechanism by which GABAergic EphB1 instructs glutamatergic axon routing is unknown
    • Whether this involves secreted signals or contact-dependent signaling between neuron types is not resolved
  19. 2025 Medium

    Extending EphB1 function to metabolic regulation: hypothalamic EphB1 activates PI3K/AKT/CREB to drive CRH and TRH expression for thermogenesis and energy homeostasis; loss causes obesity rescued by intracerebroventricular neuropeptide replacement.

    Evidence EphB1 KO mouse, primary hypothalamic neuron signaling assays, ICV peptide rescue, metabolic phenotyping

    PMID:40207393

    Open questions at the time
    • Upstream ligand activating hypothalamic EphB1 not identified
    • Whether kinase activity or scaffold function mediates CREB phosphorylation not dissected
  20. 2025 Medium

    Revealing dual downstream mechanisms in thalamic arousal circuits: EphB1 in VPM glutamatergic neurons both phosphorylates NR2B-Y1472 to enhance excitation and promotes ubiquitin-dependent KCC2 degradation to disinhibit neurons, facilitating emergence from anesthesia.

    Evidence Conditional KO in VPM, viral manipulation, in vivo electrophysiology, NR2B-Y1472 phosphorylation and KCC2 ubiquitination assays

    PMID:41348875

    Open questions at the time
    • E3 ligase responsible for KCC2 ubiquitination downstream of EphB1 not identified
    • Whether EphB1 directly phosphorylates NR2B or acts through Src/Fyn not resolved in this system

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis for EphB1's specificity over EphB2 in chiasm guidance, how the multiple phosphotyrosine-dependent signaling branches are coordinated in space and time, and the physiological interplay among SUMOylation, neddylation, and Cbl-mediated ubiquitination in regulating receptor output.
  • No full-length EphB1 structure with signaling partners resolved
  • Relative quantitative contribution of individual pY sites to specific in vivo phenotypes untested
  • Cross-regulation between SUMOylation, neddylation, and ubiquitination not addressed

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 6 GO:0098772 molecular function regulator activity 3
Localization
GO:0005886 plasma membrane 2
Pathway
R-HSA-1266738 Developmental Biology 6 R-HSA-112316 Neuronal System 4 R-HSA-392499 Metabolism of proteins 3
Partners
CAV1CBLEFNB2GRB7NCK1PAXILLINSHC1SRC

Evidence

Reading pass · 34 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 EphA4 and EphB1 receptors in migrating Xenopus neural crest cells interact with ephrin-B2 ligand expressed in adjacent arch territories; inhibition of EphB1 function via dominant-negative truncated receptors causes abnormal migration of third arch neural crest into second and fourth arch territories, establishing a repulsive boundary mechanism. Dominant-negative truncated receptor overexpression, ectopic ephrin-B2 overexpression in Xenopus embryos Current Biology High 9259557
1998 EphB1 juxtamembrane region (Tyr594) recruits the SH2-domain adaptor Nck upon ligand activation; this interaction couples EphB1 to downstream JNK/SAPK activation and cell attachment responses. Yeast two-hybrid cloning, co-immunoprecipitation, site-directed mutagenesis (Y594F), dominant-negative overexpression, kinase assay Journal of Biological Chemistry High 9430661
1999 EphB1 functions as a ligand-density sensor: engagement with ephrin-B1 displayed at varying surface densities activates integrin-mediated cell attachment (alphavbeta3 in endothelial cells; alpha5beta1 upon EphB1 transfection in HEK cells) through downstream signaling rather than mechanical tethering; signaling-defective point mutants fail to stimulate attachment. Reconstituted ephrin-B1 surface assay, integrin-blocking antibodies, EphB1 point-mutant transfection, cell attachment assay EMBO Journal High 10205170
1999 EphB1 and its ligand ephrin-B2 are expressed in complementary patterns in midbrain dopaminergic neurons; ephrin-B2 selectively inhibits neurite outgrowth and induces cell loss of substantia nigra (but not VTA) dopaminergic neurons, suggesting EphB1/ephrin-B2 specifies distinct mesostriatal vs. mesolimbic pathways. In vitro neurite outgrowth assay, cell survival assay, expression analysis Journal of Neuroscience Medium 10066262
2001 EphB1 transphosphorylates the kinase-dead EphB6 receptor in a ligand-dependent manner; EphB1 and EphB6 form a stable heterocomplex, demonstrating Eph receptor cross-talk. Additionally, c-Cbl was identified as an EphB6-binding protein in this complex. Co-immunoprecipitation, overexpression of catalytically active vs. inactive EphB1, ligand stimulation assay Journal of Biological Chemistry Medium 11713248
2002 EphB1 interacts with the adaptor Grb7 via Grb7's SH2 domain binding to phospho-Tyr928 of EphB1; EphB1 phosphorylates Grb7, and this interaction promotes fibroblast cell motility in a kinase-dependent manner. Yeast two-hybrid, co-immunoprecipitation, site-directed mutagenesis (Y928F, Y594F), cell migration assay with dominant-negative Grb7 SH2 domain Journal of Biological Chemistry High 12223469
2003 Ephrin-B2 at the optic chiasm midline selectively repels EphB1-expressing retinal ganglion cell axons from ventrotemporal retina; EphB1 null mice show dramatically reduced ipsilateral retinal projection, establishing EphB1 as the key receptor mediating retinal axon divergence at the chiasm. EphB1 knockout mouse, in vitro stripe/collapse assay with chiasm cells, blocking antibody experiments, semiintact visual system preparation Neuron High 12971893
2003 Activated EphB1 recruits Grb2 and p52Shc, promotes p52Shc and c-Src tyrosine phosphorylation, and activates MAPK/ERK to drive chemotaxis; Tyr600 and Tyr778 of EphB1 are required for interaction with c-Src and p52Shc; p52Shc phosphorylation by c-Src is required for its recruitment to EphB1 signaling complexes via its PTB domain. Co-immunoprecipitation, dominant-negative c-Src, MEK inhibitor PD98059, Src inhibitor PP2, site-directed mutagenesis (Y600F, Y778F), cell migration assay Journal of Cell Biology High 12925710
2004 Activated EphB1 induces c-Src-dependent tyrosine phosphorylation of paxillin at Tyr31 and Tyr118 and is recruited to paxillin-FAK complexes; Nck binding site Y594F mutation disrupts the EphB1–Nck–paxillin complex; paxillin Y31F/Y118F mutant cells show reduced EphB1-dependent migration. Co-immunoprecipitation, site-directed mutagenesis (Y31F/Y118F paxillin, Y594F EphB1), dominant-negative kinase-dead c-Src, PP2 inhibitor, cell migration assay Journal of Biological Chemistry High 15107421
2006 EphB1 receptors localize to caveolae via direct interaction with caveolin-1 through a caveolin-binding motif in the EphB1 kinase domain; overexpression of scaffolding-domain-deleted caveolin-1 abrogates EphB1–caveolin-1 interaction and ERK activation; the caveolin-binding motif is required for correct EphB1 membrane targeting. Sucrose density gradient fractionation, co-immunoprecipitation, dominant-negative caveolin-1, membrane targeting assay Journal of Cell Science Medium 16723736
2007 Ephrin-B1 stimulation triggers Cbl recruitment to EphB1, Cbl phosphorylation (requiring Src kinase activity), EphB1 ubiquitination, and lysosomal degradation of EphB1; kinase-dead EphB1-K652R is resistant to Cbl-mediated degradation; GST pull-down showed Cbl binds EphB1 through its tyrosine kinase-binding domain. Ubiquitination assay, lysosomal inhibitor (bafilomycin), co-immunoprecipitation, overexpression of Cbl WT vs. 70Z ligase-dead mutant, GST pull-down, Src inhibitor PP2 Traffic High 18034775
2008 Zic2 transcription factor regulates EphB1 expression in retinal ganglion cells; ectopic Zic2 delivery induces EphB1 mRNA and protein in non-ventrotemporal retinal explants, and upregulated EphB1 localizes to growth cones and is sufficient to convert RGC axon behavior from extension onto to avoidance of ephrin-B2 substrates. In utero retinal electroporation, explant growth cone collapse assay, immunofluorescence of EphB1 in growth cones Journal of Neuroscience Medium 18524895
2008 In vivo electroporation showing that ectopic EphB1 expression is sufficient to redirect normally crossed RGC axons to ipsilateral trajectory; EphB2, despite high similarity, is much less efficient; chimeric receptor analysis reveals both extracellular and juxtamembrane domains of EphB1 are required for efficient ipsilateral redirection. In utero retinal electroporation, EphB1/EphB2 chimeric receptors, anterograde tracing Journal of Neuroscience Medium 19295152
2008 EphB1 null mice exhibit a 40% decrease in neuron number and volume in substantia nigra pars reticulata (SNr) but not pars compacta (SNc), and display spontaneous locomotor hyperactivity, establishing EphB1 as required for proper SNr formation. EphB1 knockout mouse, beta-galactosidase reporter, stereological neuron counting, open-field behavioral assay European Journal of Neuroscience Medium 17561836
2009 EphB1 receptor is required for long-term potentiation (LTP) at C-fiber–spinal dorsal horn synapses in vivo; targeted mutation of EphB1 prevents HFS-induced LTP and associated upregulation of p-CaMKII, p-ERK, p-CREB, and c-Fos in the spinal cord. EphB1 knockout mouse, in vivo electrophysiology, immunoblotting for signaling markers, MK-801 and EphB2-Fc blocking Molecular Pain Medium 19523204
2011 EphB1 forward signaling in spinal cord mediates bone cancer pain; spinal EphB1 activation by ephrin-B2 phosphorylates NR1 and NR2B subunits of NMDA receptors; blocking EphB1 with EphB2-Fc reverses pain behaviors and reduces c-Fos, astrocyte/microglial activation, and Src phosphorylation within the NMDA complex; MMP-2/9 regulate EphB1 levels. EphB1 blocking reagent (EphB2-Fc), EphB1 knockout mouse, intrathecal administration, immunoblotting for NMDA subunit phosphorylation, MMP inhibitors Cancer Research Medium 21555368
2011 EphB1 forward signaling is required for ipsilateral retinal projection at the optic chiasm; knock-in of intracellularly truncated EphB1 (EphB1T-lacZ) eliminates the ipsilateral projection, confirming that EphB1 functions as a receptor (not reverse signaling source); EphB1 is the preferred receptor for ephrin-B2 (and to lesser degree ephrin-B1) at the chiasm. Knock-in mouse with intracellular truncation (EphB1T-lacZ), anterograde retinal tracing European Journal of Neuroscience High 22103419
2012 EphB1 recruits Caskin1 scaffold protein through adaptor Nck; upon EphB1 kinase activation, Caskin1 is tyrosine-phosphorylated at Y296 and Y336 (identified by mass spectrometry), and this phosphorylation causes significant structural changes in the Caskin1 SH3 domain as shown by CD spectroscopy. Co-immunoprecipitation, mass spectrometry, CD spectroscopy Cell Communication and Signaling Medium 23181695
2012 PTEN constitutively associates with c-Cbl, protecting Cbl from degradation; EphB1 stimulation triggers PTEN dephosphorylation (requiring PTEN protein phosphatase activity) and disruption of the PTEN–Cbl complex, allowing independent translocation of both proteins to EphB1 via scaffold NHERF1; PTEN lipid phosphatase activity impairs EphB1-dependent cell adhesion and chemotaxis. Co-immunoprecipitation, PTEN/NHERF1 siRNA, PTEN phosphatase mutants, cell adhesion and migration assay FASEB Journal Medium 23118026
2014 EphB1 expressed in striatal anlage signals through ephrin-B3 reverse signaling with dual context-dependent outcomes: in cortical interneurons EphB1-ephrinB3 reverse signaling phosphorylates Src and FAK to mediate repulsion, whereas in striatal neurons it reduces endogenously high pSrc and pFAK to act as a stop signal; ephrin-B3 knockout mice show misrouted cortical interneurons in the striatum and over-migration of striatal neurons. Ephrin-B3 knockout mouse, in vitro migration assays, immunoblotting for pSrc and pFAK Frontiers in Cellular Neuroscience Medium 25100946
2015 Intracellular signaling domains of EphB1 and EphB2 are critical for formation of the corpus callosum and anterior commissure; truncated EphB1/EphB2 mice lacking intracellular domains show partial/complete agenesis of corpus callosum and highly penetrant anterior commissure misprojection, indicating combined forward and reverse signaling contributions. Truncated receptor knock-in mice, anterograde tract tracing, brain anatomy analysis Developmental Neurobiology Medium 26148571
2017 Injured motor neurons upregulate EphB1, which activates astrocytes through ephrin-B1-mediated STAT3 stimulation to induce a protective anti-inflammatory transcriptional signature; this EphB1–ephrin-B1–STAT3 pathway is disrupted in human stem-cell-derived ALS astrocytes and mouse ALS models. Human iPSC-derived astrocytes, mouse ALS models, transcriptional analysis, STAT3 pathway activation assay Nature Communications Medium 29079839
2018 Porf-2, a neuronally expressed RhoGAP, binds EphB1 and is regulated downstream; activated EphB1 forward signaling deactivates Rac1 through the Porf-2 GAP domain, inhibiting growth cone expansion and braking axon growth. Co-immunoprecipitation, Rac1 activity assay (pull-down), Porf-2 GAP domain mutants, axon growth assay Cellular and Molecular Life Sciences Medium 29938386
2018 EphB1 is SUMOylated at lysine 785; SUMOylation-deficient K785R mutant shows enhanced cell proliferation, anchorage-independent growth, and xenograft tumor growth; mechanistically, EphB1 SUMOylation represses activation of PKCγ, and a reciprocal regulatory loop between PKCγ and EphB1 SUMOylation exists. Ni2+-NTA pull-down, co-immunoprecipitation, K785R mutant, xenograft mouse model, soft agar colony assay, PKCγ activation assay Cellular Physiology and Biochemistry Medium 29550816
2020 EphB1 constitutively interacts with caveolin-1 (Cav-1) via its CSD-binding motif; upon ephrin-B1 activation, EphB1 is phosphorylated and uncouples from Cav-1, enabling Src-dependent Cav-1 phosphorylation; loss of EphB1 promotes Cav-1 ubiquitination and degradation, reducing caveolae numbers in endothelial cells. Super-resolution microscopy, FRET, co-immunoprecipitation, EphB1-/- mice endothelial cells, CSD deletion mutant, Cav-1 ubiquitination assay Molecular Biology of the Cell High 32238105
2020 TGF-β–activated Smad2 transcriptionally upregulates EphB1 expression; ligand-independent (unphosphorylated) EphB1 promotes EMT and lung cancer cell migration/invasion through upregulation of CDH2 (N-cadherin), while ligand-dependent (phosphorylated) EphB1 inhibits these processes. Western blot, real-time PCR, transwell migration/invasion assay, EphB1 phosphorylation-deficient mutant, Smad2 overexpression Journal of Cancer Medium 32368295
2021 Tetracyclines (demeclocycline, chlortetracycline, minocycline) inhibit EphB1 kinase activity at low micromolar concentrations by binding the ATP-binding catalytic domain; co-crystal structure of chlortetracycline with EphB1 confirmed this binding; in vivo administration inhibited EphB1 phosphorylation in spinal cord/DRG and blocked neuropathic pain. In silico docking, in vitro kinase assay, co-crystallization (crystal structure), in vivo phosphorylation assay, neuropathic pain mouse model PNAS High 33627480
2023 EphB1 is neddylated in activated hepatic stellate cells; neddylation enhances EphB1 kinase activity by preventing its degradation, thereby promoting HSC proliferation, migration, and activation contributing to liver fibrosis. Immunoprecipitation, neddylation inhibitor, EphB1 kinase activity assay, HSC functional assays International Journal of Molecular Sciences Medium 36834826
2023 CRC-associated somatic mutations in EphB1 kinase domain reduce kinase activity and protein stability in vitro; mutant EphB1 receptors fail to suppress STAT3 and ERK1/2 signaling and are unable to suppress CRC cell migration or mediate cell compartmentalization when cocultured with ephrin-B1-expressing cells. Purified kinase domain assay, thermal stability assay, cell migration assay, cell compartmentalization coculture assay, western blot for STAT3/ERK signaling Journal of Biological Chemistry High 37527777
2023 Recurring EPHB1 cancer mutations in ligand-binding, fibronectin, and kinase domains reduce ligand-induced receptor phosphorylation and cell compartmentalization; enhanced compartmentalization mutations in kinase domain (R743W, G821R) are not linked to phosphorylation level; reduced compartmentalization mutants activate PIK3C2B phosphorylation via the PI3K pathway. Confocal microscopy compartmentalization assay, phospho-proteome mass spectrometry, bioinformatic 3D-cluster analysis Cell Communication and Signaling Medium 38102712
2024 EphB1 conditional knockout specifically in GABAergic neurons (Vgat-Cre) but not cortical excitatory neurons (Emx1-Cre) or endothelial cells (Tie2-Cre) reproduces cortical axon guidance defects seen in global EphB1 KO; EphB1 in GABAergic neurons promotes avoidance of ectopic fasciculation with brain vasculature by glutamatergic cortical axons. Cell-type specific conditional knockout (Vgat-Cre, Emx1-Cre, Tie2-Cre), anterograde tract tracing Development Medium 38345254
2024 Tumor cell-expressed EPHB1 and platelet-expressed EFNB1 mediate contact-dependent reverse signaling activation of platelets via AKT pathway; activated platelets then release 5-HT which enhances tumor growth in the liver metastatic niche of pancreatic ductal adenocarcinoma. Gain- and loss-of-function of Ephb1, recombinant protein assays, Tph1-knockout mice (5-HT depletion), tumor-platelet adhesion assay, metastasis mouse model Cancer Communications Medium 39648610
2025 EphB1 promotes CREB phosphorylation via PI3K/AKT signaling in a cell-autonomous manner in hypothalamic neurons; EphB1 deficiency reduces CRH and TRH expression in hypothalamus, causing impaired thermogenesis, reduced locomotor activity, and obesity; intracerebroventricular TRH or CRH peptide rescues obesity in Ephb1 mutants. Forward genetic screen, EphB1 knockout mouse, primary hypothalamic cell signaling assay, intracerebroventricular peptide administration, metabolic phenotyping Obesity Medium 40207393
2025 EphB1 activation in thalamic ventroposteromedial nucleus (VPM) glutamatergic neurons promotes emergence from anesthesia via two independent mechanisms: (1) phosphorylation of NMDA receptor NR2B subunit at Tyr1472, exciting VPMGlu neurons; and (2) ubiquitin-dependent degradation of KCC2, disinhibiting VPMGlu neurons that project to primary somatosensory cortex. EphB1 conditional knockout in VPM, site-specific viral vector manipulation, in vivo electrophysiology, immunoblotting for NR2B-Y1472 phosphorylation and KCC2 ubiquitination, behavioral anesthesia emergence assay Science Advances Medium 41348875

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 281 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 177 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 82 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 34 17255342
2013 Involvement of EphB1 receptors signalling in models of inflammatory and neuropathic pain. PloS one 33 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
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 EphB1 interaction with caveolin-1 in endothelial cells modulates caveolae biogenesis. Molecular biology of the cell 10 32238105
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 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
2024 EphB1 controls long-range cortical axon guidance through a cell non-autonomous role in GABAergic cells. Development (Cambridge, England) 3 38345254
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