Affinage

EPHA3

Ephrin type-A receptor 3 · UniProt P29320

Length
983 aa
Mass
110.1 kDa
Annotated
2026-06-09
100 papers in source corpus 25 papers cited in narrative 26 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

EphA3 is a receptor tyrosine kinase that converts ephrin-A ligand engagement into cytoskeletal remodeling, controlling cell adhesion, migration, axon guidance, and tissue morphogenesis (PMID:11870224, PMID:18814179). It binds GPI-anchored ephrin-A ligands with high affinity through an N-terminal ligand-binding region encoded by exon III, while a separate C-terminal domain drives ligand-independent receptor oligomerization, defining a two-step activation mechanism (PMID:9685371, PMID:7838529); assembly of signaling-competent oligomers depends on three distinct surface interfaces of the receptor (PMID:14660665), and unliganded receptor dimers are additionally stabilized by the cytoplasmic SAM domain (PMID:26232493). Kinase activity is held in check by the unphosphorylated juxtamembrane segment, which engages the active site until autophosphorylation of two juxtamembrane tyrosines relieves autoinhibition through a coupled network of residues linking the juxtamembrane region to the activation loop (PMID:18547520). Activated EphA3 recruits the adaptors CrkII and Nck1 — the latter via its SH2 domain binding phosphotyrosine Y602 — and signals through Y602 together with Y779 to activate RhoA and suppress adhesion to fibronectin, cell migration, neurite outgrowth, and growth cone collapse (PMID:11870224, PMID:19505147, PMID:20697431, PMID:18814179). A cis-interaction with ephrinA5 on the same cell surface, independent of the canonical ligand-binding domain, silences receptor phosphorylation and converts uniform EphA3 expression into a functional sensitivity gradient in retinal axons (PMID:16491080), and presenilin-1/γ-secretase cleavage of EphA3 generates an intracellular domain that binds non-muscle myosin IIA and increases its Ser1943 phosphorylation to promote axon elongation while inhibiting RhoA (PMID:31577226). EphA3 is required for atrioventricular endocardial cushion development and epithelial-to-mesenchymal transformation in the heart (PMID:17046737). In cancer, EphA3 has kinase- and ephrin-dependent tumor-suppressing activity that is disrupted by somatic mutations impairing kinase activity, ligand binding, or surface localization — some acting as dominant negatives — and wild-type re-expression promotes apoptosis by suppressing AKT (PMID:22242939, PMID:22829656, PMID:27101199). Its expression is controlled by DNA methylation, HIF-1α, and an androgen receptor/SP1 complex binding the core promoter (PMID:10498621, PMID:25420155, PMID:29917167), and at the cell surface neurocan blocks NCAM/EphA3 complex formation and clustering to inhibit ephrin-A5-induced growth cone collapse (PMID:29670169).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1995 High

    Establishing the ligands of an orphan-like receptor was prerequisite to any mechanistic model; this work isolated high-affinity GPI-anchored ephrin-A ligands for EphA3.

    Evidence Expression cloning using soluble EphA3-Fc as an affinity probe in a human T-lymphoma line

    PMID:7838529

    Open questions at the time
    • Did not resolve how ligand binding triggers receptor activation
    • Ligand specificity overlapped with the related ELK receptor
  2. 1998 High

    How a single ligand-binding event produces an active receptor was unclear; mapping distinct ligand-binding and oligomerization subdomains established a two-step activation mechanism.

    Evidence BIAcore kinetics, zebrafish mRNA injection, and transphosphorylation of recombinant subdomains

    PMID:9685371

    Open questions at the time
    • Atomic-level interfaces not yet defined
    • Did not address downstream effectors
  3. 2002 High

    The downstream consequence of activation was undefined; ephrin-A5 clustering was shown to activate RhoA and recruit CrkII to drive cytoskeletal collapse and cell detachment.

    Evidence RhoA activation assays, CrkII Co-IP, dominant-negative CrkII rescue, and morphological assays in 293T and melanoma cells

    PMID:11870224

    Open questions at the time
    • Did not map the receptor docking site for CrkII
    • Link between RhoA and specific cytoskeletal machinery unresolved
  4. 2003 High

    The structural determinants of ligand-driven oligomerization were unknown; a mutagenesis screen identified three surface areas required for signaling-competent complex assembly, one outside known interaction domains.

    Evidence Random mutagenesis in yeast with selection for impaired ephrin-A5 binding and functional validation

    PMID:14660665

    Open questions at the time
    • Function of the third, structurally uncharacterized interface not mechanistically explained
  5. 2003 High

    EphA3 expression predicted a role in motor axon guidance; a clean knockout showed motor axons reach correct targets without EphA3, refining the receptor's in vivo guidance role.

    Evidence EphA3 null mice with retrograde axonal labeling of motor projections

    PMID:14585969

    Open questions at the time
    • Did not exclude redundancy with other Eph receptors
    • Other guidance contexts left untested
  6. 2006 High

    How uniform receptor expression yields graded responsiveness was unexplained; a cis-interaction with ephrinA5 was shown to silence receptor phosphorylation and convert expression into a functional gradient.

    Evidence FRET imaging, ephrinA5 point mutants, phosphorylation assays, and retinal axon sensitivity assays

    PMID:16491080

    Open questions at the time
    • Structural basis of the cis-interface not defined
    • Extent of cis-silencing in non-retinal tissues unknown
  7. 2006 High

    A developmental requirement for EphA3 was undefined; knockout mice revealed it is required for endocardial cushion development and EMT in the heart.

    Evidence EphA3 null mice with cardiac morphology, cushion explant migration assays, and ligand co-expression analysis

    PMID:17046737

    Open questions at the time
    • Downstream signaling driving cushion EMT not dissected
    • Cell-autonomy of the requirement not established
  8. 2008 High

    How kinase activity is restrained was unknown; crystallography revealed juxtamembrane autoinhibition relieved by autophosphorylation through a coupled residue network.

    Evidence X-ray crystallography of multiple kinase-domain states plus juxtamembrane tyrosine mutagenesis

    PMID:18547520

    Open questions at the time
    • Did not connect autoinhibition release to specific downstream substrates
    • Kinetics of the activation transition in cells unresolved
  9. 2009 High

    The receptor effector linking activation to migration suppression was unidentified; Nck1 was shown to bind phosphoY602 via its SH2 domain to mediate inhibition of migration and process retraction.

    Evidence Yeast two-hybrid, GST pulldown, Co-IP, Y602 mutagenesis, and dominant-negative Nck1 rescue with migration assays

    PMID:19505147

    Open questions at the time
    • Only partial rescue indicates additional effectors
    • Connection between Nck1 and RhoA not directly traced
  10. 2010 High

    Whether a single docking site sufficed for cytoskeletal output was untested; Y602 and Y779 were shown to act collaboratively, with full effect requiring both.

    Evidence Tyrosine-to-phenylalanine mutagenesis with migration, neurite outgrowth, and growth cone collapse assays across cell types

    PMID:20697431

    Open questions at the time
    • Effectors binding Y779 not identified
    • Mechanism of cooperativity between the two sites unresolved
  11. 2012 High

    The disease relevance of EphA3 mutations was unclear; cancer-derived mutations were shown to impair kinase activity, ligand binding, or surface localization, with some acting as dominant negatives over wild-type tumor-suppressive signaling.

    Evidence Biochemical kinase, binding, and surface-localization assays on mutant panels plus AKT signaling, apoptosis, and xenograft assays

    PMID:22242939 PMID:22829656

    Open questions at the time
    • Tumor-suppressor mechanism beyond AKT suppression incompletely defined
    • Context dependence of suppressor vs oncogenic roles unresolved
  12. 2014 Medium

    How EphA3 contributes to tumors via the microenvironment was unknown; agonist antibody activation of EphA3+ stromal cells was shown to drive contraction, segregation, and apoptosis, disrupting tumor stroma and vasculature.

    Evidence EphA3 agonist antibody on isolated stromal cells with contraction/apoptosis assays and in vivo xenograft treatment

    PMID:25125683

    Open questions at the time
    • Single lab
    • Molecular signaling underlying stromal apoptosis not detailed
  13. 2015 High

    Whether receptor dimers exist before ligand binding was untested; live-cell FRET showed unliganded dimers stabilized by the SAM domain.

    Evidence Quantitative FRET dimerization assay with SAM-deletion mutants on live cells

    PMID:26232493

    Open questions at the time
    • Functional consequence of pre-formed dimers for signaling output not established
    • SAM-mediated interface not structurally resolved
  14. 2018 High

    A surface mechanism restraining EphA3 clustering was unknown; neurocan was shown to block NCAM/EphA3 complex formation by binding the EphA3-binding site on NCAM Ig2, inhibiting kinase activation and growth cone collapse.

    Evidence Co-IP, NCAM Ig-domain binding-site mapping, clustering imaging, kinase activation, and growth cone collapse assays

    PMID:29670169

    Open questions at the time
    • Whether neurocan regulation operates outside cortical interneurons untested
  15. 2018 High

    Transcriptional control of EphA3 was incompletely mapped; an androgen-receptor/SP1 complex was shown to bind the core promoter and drive androgen-stimulated expression.

    Evidence Promoter luciferase deletion, AR/SP1 perturbation, Co-IP, and ChIP at the EPHA3 promoter

    PMID:29917167

    Open questions at the time
    • Downstream consequence of AR-driven EphA3 in prostate cancer not functionally tied to signaling
  16. 2019 High

    A ligand-independent signaling output of EphA3 was undefined; presenilin/γ-secretase cleavage was shown to release an ICD that binds NMIIA, raises its Ser1943 phosphorylation, and promotes axon elongation while inhibiting RhoA.

    Evidence Genetic rescue in PS1/EphA3-deficient neurons, ICD interactome proteomics, NMIIA phosphorylation assays, and pharmacological NMII inhibition

    PMID:31577226

    Open questions at the time
    • Trigger for cleavage in vivo not defined
    • Balance between full-length signaling and ICD function unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the receptor's context-dependent switch between tumor-suppressive full-length signaling, microenvironmental effects, and ligand-independent ICD functions is coordinated at the molecular level remains unresolved.
  • No unified model integrating full-length kinase signaling, cis-silencing, and ICD output
  • Effectors downstream of Y779 not identified
  • Mechanistic basis of EZH2/DNMT1-mediated PTEN regulation remains correlative

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 3 GO:0001618 virus receptor activity 2 GO:0016740 transferase activity 2 GO:0140096 catalytic activity, acting on a protein 2 GO:0060090 molecular adaptor activity 1
Localization
GO:0005886 plasma membrane 3
Pathway
R-HSA-1266738 Developmental Biology 3 R-HSA-162582 Signal Transduction 3 R-HSA-1643685 Disease 3
Partners
CRKEFNA1EFNA5MYH9NCAM1NCK1PSEN1
Complex memberships
NCAM/EphA3 complex

Evidence

Reading pass · 26 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 EphA3 extracellular region contains distinct functional subdomains: ligand binding is restricted to the N-terminal region encoded by exon III, while an independent C-terminal domain mediates receptor dimerization/oligomerization. A two-step activation mechanism was proposed involving sequential ligand binding and ligand-independent receptor-receptor oligomerization. BIAcore kinetic binding analysis, mRNA injection into zebrafish embryos, receptor transphosphorylation analysis using recombinant subdomain proteins The Journal of biological chemistry High 9685371
1995 EphA3 (hek) binds GPI-anchored membrane proteins (ephrin-A ligands) with high affinity (Kd ~2×10^8 M^-1); two related ephrin ligands were isolated from a human T-lymphoma line that bind both EphA3 and the related ELK receptor tyrosine kinase. Expression cloning using soluble EphA3-Fc fusion protein as affinity probe; binding affinity measured by Fc-fusion pulldown Oncogene High 7838529
2002 Ephrin-A5 stimulation of EphA3 causes rapid RhoA activation, leading to actin/myosin cytoskeleton reorganization, membrane blebbing, retraction of cellular protrusions, and cell detachment. Receptor clustering (polymeric ephrin-A5) is required. The adaptor CrkII associates with tyrosine-phosphorylated EphA3 in vitro and is recruited in vivo upon ephrin-A5 stimulation; expression of SH3-domain-mutated CrkII abolishes cell rounding, blebbing, and detachment. Ephrin-A5 stimulation assays, RhoA activation assay, co-immunoprecipitation of CrkII with phosphorylated EphA3, dominant-negative CrkII expression, morphological assays in EphA3-expressing 293T and melanoma cells Journal of cell science High 11870224
2003 Three distinct surface areas of EphA3 are essential for ephrin-A5 binding and assembly of signaling-competent oligomeric receptor-ligand complexes: two map to interfaces identified in the EphB2-ephrin-B2 crystal structure, and a third falls outside the structurally characterized interaction domains. Random mutagenesis of EphA3 in yeast expression library, selection for impaired ephrin-A5 binding, functional characterization of point mutants The Journal of biological chemistry High 14660665
2006 EphA3 forms a cis-interaction with ephrinA5 (on the same cell surface) that is independent of the established ligand-binding domain of EphA3. This cis-complex abolishes ephrinA5-induced tyrosine phosphorylation of EphA3 and renders retinal axons insensitive to ephrinA in trans, thereby converting uniform EphA3 expression into a functional gradient. Truncated EphA3 constructs, single-amino acid point mutants of ephrinA5, FRET (fluorescence resonance energy transfer) imaging, tyrosine phosphorylation assays, retinal axon sensitivity assays Nature neuroscience High 16491080
2006 EphA3 signaling is required for atrioventricular endocardial cushion development and epithelial-to-mesenchymal transformation (EMT) in the developing heart. EphA3 knockout mice show hypoplastic endocardial cushions and reduced mesenchymal cell migration from cushion explants; EphA3 and its ligand ephrin-A1 are expressed in adjacent cells in the developing endocardial cushions. EphA3 null mouse generation, cardiac morphological analysis, endocardial cushion explant migration assay, expression analysis by in situ/immunostaining Developmental biology High 17046737
2008 The unphosphorylated juxtamembrane (JM) region of EphA3 inhibits kinase activity through an autoinhibitory mechanism: two tyrosines in the JM region are sites of autophosphorylation and interact with the kinase active site to modulate catalysis. Crystal structures of multiple states (with/without JM segment, wild-type and mutants) revealed a conserved pathway of coupled residues connecting the JM segment to the activation loop and catalytic residues. X-ray crystallography of EphA3 kinase domain with and without juxtamembrane segment; site-specific mutagenesis of JM tyrosines; structural comparison of multiple states Structure High 18547520
2009 Adaptor protein Nck1 interacts with activated EphA3 through binding of the Nck1 SH2 domain to phosphotyrosine Y602 of EphA3. This interaction mediates EphA3-induced inhibition of cell migration and process retraction; dominant-negative Nck1 mutants lacking functional SH2 or SH3 domains partially alleviate the EphA3-mediated inhibitory effects. Yeast two-hybrid screen using EphA3 cytoplasmic domain as bait; GST pulldown; co-immunoprecipitation; Y602 point mutagenesis; dominant-negative Nck1 rescue experiments; cell migration and process retraction assays Biochemistry High 19505147
2010 EphA3-mediated inhibition of cell migration, neurite outgrowth, and growth cone collapse requires collaboration between phosphotyrosine residues Y602 and Y779 in the cytoplasmic domain. Mutation of either residue alone partially decreases EphA3-induced responses; full abrogation requires mutation of both Y602 and Y779 together. Individual tyrosine-to-phenylalanine mutagenesis of EphA3 cytoplasmic domain residues; cell migration assay (293A cells); neurite outgrowth assay (NG108-15 cells); growth cone collapse assay (hippocampal neurons) Cell research High 20697431
2012 Somatic cancer mutations in EphA3 impair kinase activity and/or ephrin ligand binding and/or decrease receptor cell surface localization through multiple distinct mechanisms, consistent with EphA3 having ephrin- and kinase-dependent tumor-suppressing activities disrupted by cancer mutations. Functional analysis of cancer-derived EphA3 point mutants: in vitro kinase assays, ephrin binding assays, cell surface biotinylation/flow cytometry Biochemistry High 22242939
2012 At least two cancer-associated EphA3 somatic mutations function as dominant inhibitors (dominant negative) of wild-type EphA3 protein. Wild-type EphA3 re-expression in lung cancer lines increases apoptosis by suppressing AKT activation in vitro and inhibits tumor xenograft growth in vivo; dominant-negative mutations override these tumor-suppressive effects in trans. Immunoprecipitation, western blotting, kinase assays; AKT phosphorylation analysis; BrdU proliferation and apoptosis assays; xenograft tumor growth assay Journal of the National Cancer Institute High 22829656
2013 EphA3 maintains glioblastoma tumor-initiating cells in a less differentiated state by modulating MAPK signaling. EphA3 knockdown or depletion of EphA3-positive cells reduces tumorigenic potential. EphA3 knockdown (siRNA/shRNA), tumor sphere formation, MAPK signaling analysis, xenograft mouse model, radiolabeled EphA3 antibody depletion of EphA3+ cells Cancer cell Medium 23410976
2005 The anti-EphA3 monoclonal antibody IIIA4 binds a conformation-specific epitope within the ephrin-binding domain adjacent to the ephrin-A5 heterotetramerization site. Preclustered IIIA4 triggers EphA3 activation and cytoskeletal contraction similarly to ephrin-A5. Unclustered IIIA4 and ephrin-A5 Fc in combination initiate greatly enhanced EphA3 signaling through allosteric permissive conformational effects. BIAcore binding analysis, immunoblot for EphA3 phosphorylation, confocal microscopy, wild-type and binding-site mutant EphA3 analysis, cell contraction assays Cancer research High 16061656
2015 EphA3 forms dimers in the absence of ligand binding on the surface of live cells, and these unliganded dimers are stabilized by interactions involving the EphA3 SAM (sterile α-motif) domain, establishing a new role for the SAM domain in promoting Eph receptor lateral interactions. Quantitative FRET-based dimerization assay on live cells, deletion mutants removing the SAM domain, comparison of wild-type vs. SAM-deleted EphA3 The Biochemical journal High 26232493
2019 Presenilin-1 (PS1)/γ-secretase cleaves EphA3 independently of ligand binding to generate an intracellular domain (ICD) fragment. EphA3 ICD promotes axon elongation by binding to non-muscle myosin IIA (NMIIA) and increasing its phosphorylation at Ser1943, promoting NMIIA filament disassembly and cytoskeletal rearrangement. This PS/EphA3-dependent cleavage also inhibits RhoA signaling to promote axon growth. Genetic rescue experiments in PS1/γ-secretase- and EphA3-deficient hippocampal neurons; proteomic analysis of EphA3 ICD binding partners; NMIIA phosphorylation assays; pharmacological NMII inhibition; RhoA signaling assays; live imaging eLife High 31577226
2009 Stimulation of EphA3 with ephrin-A5 inhibits cell migration and process outgrowth; these effects are partially mediated through the Nck1 SH2-SH3 adaptor protein binding phosphoY602. Dominant-negative Nck1 (lacking functional SH2 or SH3) partially rescues the inhibitory effects, indicating Nck1 is a downstream effector of EphA3-mediated cytoskeletal responses. Cell migration assays, process retraction assay, dominant-negative Nck1 expression, co-immunoprecipitation Biochemistry High 19505147
2004 EphA3 stimulation by ephrin-A5 in Jurkat and RMS cells causes loss of cell adhesion to fibronectin and recruitment of CrkII to EphA3. EphA3 expression is transcriptionally upregulated by CD28 co-stimulation and by IGF-1/IGF-1R signaling; anti-IGF-1R blocking antibodies suppress this upregulation. Receptor array screening, ephrin-A5 stimulation assays, Co-IP of CrkII with EphA3, western blotting, anti-IGF-1R blocking antibody experiments Experimental cell research Medium 14697337
2008 EphA3 stimulation with ephrin-A5 increases EphA3 phosphorylation and Rho GTPase activity in rhabdomyosarcoma cells, resulting in suppression of cell adhesion to fibronectin and decreased migration toward SDF-1. EphA3 siRNA knockdown increases SDF-1-mediated motility, confirming a suppressive role in cell motility. Ephrin-A5 stimulation, phosphorylation assays, Rho GTPase activity assay, fibronectin adhesion assay, Transwell migration assay, siRNA knockdown Journal of cellular biochemistry Medium 18814179
2018 Neurocan (a perineuronal net proteoglycan) binds NCAM at the EphA3-binding site within the immunoglobulin-2 domain of NCAM, inhibiting NCAM/EphA3 association, membrane clustering of NCAM/EphA3, EphA3 kinase activation, and ephrin-A5-induced growth cone collapse in cortical interneuron axons. Co-immunoprecipitation of neurocan with NCAM, binding site mapping using NCAM-Ig domain mutants, EphA3 kinase activation assays, NCAM/EphA3 clustering assay by imaging, growth cone collapse assay in cortical neurons Scientific reports High 29670169
1999 EphA3 expression in hematopoietic tumor cell lines is regulated by DNA methylation of CpG sites downstream of the basal promoter; these methylation sites are absent in normal tissues but present in leukemia patient samples, indicating epigenetic regulation of EphA3 transcription. Promoter deletion/reporter assays; Southern blot with methylation-sensitive restriction enzymes; bisulfite sequencing of genomic DNA from cell lines and clinical leukemia samples Blood High 10498621
2014 EphA3 is highly expressed on bone marrow-derived mesenchymal/stromal cells (CD90+/Sca1+) and myeloid cells within the tumor microenvironment. Activation of EphA3+ mesenchymal/stromal cells with an agonistic EphA3 antibody leads to cell contraction, cell-cell segregation, and apoptosis, disrupting newly formed tumor stroma and microvasculature and inhibiting tumor growth in vivo. EphA3 agonist antibody treatment of isolated stromal cells, cell contraction/segregation assays, apoptosis assays, in vivo mouse xenograft model with α-EphA3 antibody treatment Cancer research Medium 25125683
2014 HIF-1α controls EphA3 expression on human endometrial multipotent mesenchymal stromal cells (eMSCs) under hypoxic conditions. EphA3 silencing significantly inhibits the ability of transplanted eMSCs to support neovascularisation in immunocompromised mice, placing EphA3 downstream of HIF-1α in stromal cell-mediated vascular support. HIF-1α-EphA3 expression correlation, EphA3 siRNA knockdown in eMSCs, in vivo neovascularization assay in NSG mice PloS one Medium 25420155
2016 EPHA3 overexpression in small cell lung cancer cells decreases chemoresistance by increasing apoptosis and inducing G0/G1 arrest, accompanied by reduced phosphorylation of the PI3K/BMX/STAT3 signaling pathway. Conversely, EPHA3 knockdown generates a resistant phenotype with increased PI3K/BMX/STAT3 phosphorylation; PI3K inhibitor (LY294002) and BMX inhibitor (LFM-A13) both reverse the EPHA3-deficiency-induced resistance. EPHA3 overexpression and siRNA knockdown in SCLC cells; PI3K/BMX/STAT3 phosphorylation western blots; apoptosis and cell cycle assays; pharmacological inhibitor rescue; in vivo xenograft Tumour biology Medium 27101199
2021 EPHA3 regulates PTEN expression epigenetically in radioresistant head and neck cancer cells via two mechanisms downstream of EPHA3/c-Myc signaling: DNMT1-mediated DNA methylation and EZH2-mediated histone H3K27 trimethylation of the PTEN promoter. Western blotting for DNMT1, EZH2, H3K27me3, and PTEN in radioresistant vs. sensitive cells; EPHA3 knockdown/overexpression; correlation of EPHA3 levels with DNMT1/EZH2/H3K27me3/PTEN Biomolecules Low 33919657
2018 Androgen receptor (AR) induces EPHA3 expression in prostate cancer cells by forming a transcription factor complex with SP1 that binds SP1 binding sites (−295 to −261) in the EPHA3 core promoter region, as required for androgen-stimulated EPHA3 transcription. Luciferase reporter assays with EPHA3 promoter deletion constructs; AR overexpression and siRNA knockdown; SP1 inhibitor (mithramycin A) and siSP1 treatment; co-immunoprecipitation and chromatin immunoprecipitation (ChIP) of AR/SP1 complex at EPHA3 promoter Oncology reports High 29917167
2003 EphA3(-/-) null mice do not show defects in motor axon guidance to axial muscle targets, contrary to prior prediction based on EphA3 expression in the medial motor column; retrograde labeling studies confirm motor axons reach correct targets without EphA3. EphA3 null mouse generation; retrograde axonal labeling of motor projections in embryos and adults Molecular and cellular biology High 14585969

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1997 Protein kinase C activation regulates human serotonin transporters in HEK-293 cells via altered cell surface expression. The Journal of neuroscience : the official journal of the Society for Neuroscience 307 8987735
2013 EphA3 maintains tumorigenicity and is a therapeutic target in glioblastoma multiforme. Cancer cell 175 23410976
2006 Silencing of EphA3 through a cis interaction with ephrinA5. Nature neuroscience 155 16491080
2002 Ephrin-A5 induces rounding, blebbing and de-adhesion of EphA3-expressing 293T and melanoma cells by CrkII and Rho-mediated signalling. Journal of cell science 149 11870224
1998 Comparison of Na-K-Cl cotransporters. NKCC1, NKCC2, and the HEK cell Na-L-Cl cotransporter. The Journal of biological chemistry 110 9556622
2018 Nose-to-brain delivery of temozolomide-loaded PLGA nanoparticles functionalized with anti-EPHA3 for glioblastoma targeting. Drug delivery 92 30176744
1998 Distinct subdomains of the EphA3 receptor mediate ligand binding and receptor dimerization. The Journal of biological chemistry 86 9685371
1995 Ligands for the receptor tyrosine kinases hek and elk: isolation of cDNAs encoding a family of proteins. Oncogene 83 7838529
2003 Dissecting the EphA3/Ephrin-A5 interactions using a novel functional mutagenesis screen. The Journal of biological chemistry 77 14660665
2014 Targeting EphA3 inhibits cancer growth by disrupting the tumor stromal microenvironment. Cancer research 67 25125683
2004 D1 dopamine receptor signaling involves caveolin-2 in HEK-293 cells. Kidney international 66 15569306
2005 Concurrent binding of anti-EphA3 antibody and ephrin-A5 amplifies EphA3 signaling and downstream responses: potential as EphA3-specific tumor-targeting reagents. Cancer research 65 16061656
1999 Cloning and characterization of EphA3 (Hek) gene promoter: DNA methylation regulates expression in hematopoietic tumor cells. Blood 65 10498621
1993 PCR mediated detection of a new human receptor-tyrosine-kinase, HEK 2. Oncogene 64 8397371
2006 Somatic mutations of GUCY2F, EPHA3, and NTRK3 in human cancers. Human mutation 63 16941478
2006 A critical role for the EphA3 receptor tyrosine kinase in heart development. Developmental biology 60 17046737
2003 Protein kinase C-mediated Ca2+ entry in HEK 293 cells transiently expressing human TRPV4. British journal of pharmacology 59 12970074
2021 Intranasal Delivery of Temozolomide-Conjugated Gold Nanoparticles Functionalized with Anti-EphA3 for Glioblastoma Targeting. Molecular pharmaceutics 57 33417456
2012 Cancer somatic mutations disrupt functions of the EphA3 receptor tyrosine kinase through multiple mechanisms. Biochemistry 54 22242939
2012 Effects of cancer-associated EPHA3 mutations on lung cancer. Journal of the National Cancer Institute 53 22829656
2008 Autoregulation by the juxtamembrane region of the human ephrin receptor tyrosine kinase A3 (EphA3). Structure (London, England : 1993) 53 18547520
2014 EphA3 biology and cancer. Growth factors (Chur, Switzerland) 52 25391995
1995 G protein beta gamma subunit activates Ras, Raf, and MAP kinase in HEK 293 cells. FEBS letters 51 7615078
2014 PACAP-induced ERK activation in HEK cells expressing PAC1 receptors involves both receptor internalization and PKC signaling. American journal of physiology. Cell physiology 48 24696141
2003 Expression of Drosophila trehalose-phosphate synthase in HEK-293 cells increases hypoxia tolerance. The Journal of biological chemistry 47 13129920
2005 Endogenous channels in HEK cells and potential roles in HCN ionic current measurements. Progress in biophysics and molecular biology 45 15979128
2015 Unliganded EphA3 dimerization promoted by the SAM domain. The Biochemical journal 44 26232493
2012 Aberrant expression of EphA3 in gastric carcinoma: correlation with tumor angiogenesis and survival. Journal of gastroenterology 44 22350700
2014 DNA damage and S phase arrest induced by Ochratoxin A in human embryonic kidney cells (HEK 293). Mutation research 43 25847125
2018 N-Glycosylation of Extracellular Vesicles from HEK-293 and Glioma Cell Lines. Analytical chemistry 42 29888905
2004 EphA3 is induced by CD28 and IGF-1 and regulates cell adhesion. Experimental cell research 40 14697337
2005 Upregulation of EphA3 receptor after spinal cord injury. Journal of neurotrauma 38 16083359
2004 Functional expression and cellular distribution of diastrophic dysplasia sulfate transporter (DTDST) gene mutations in HEK cells. Human molecular genetics 38 15294877
2016 EPHA3 regulates the multidrug resistance of small cell lung cancer via the PI3K/BMX/STAT3 signaling pathway. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 37 27101199
2013 Human respiratory syncytial virus N, P and M protein interactions in HEK-293T cells. Virus research 36 23892143
2017 High-Throughput Lipidomic and Transcriptomic Analysis To Compare SP2/0, CHO, and HEK-293 Mammalian Cell Lines. Analytical chemistry 35 27991764
2011 Phosphorylation and transport in the Na-K-2Cl cotransporters, NKCC1 and NKCC2A, compared in HEK-293 cells. PloS one 35 21464992
2008 The EphA3 receptor is expressed in a subset of rhabdomyosarcoma cell lines and suppresses cell adhesion and migration. Journal of cellular biochemistry 32 18814179
2018 Perineuronal Net Protein Neurocan Inhibits NCAM/EphA3 Repellent Signaling in GABAergic Interneurons. Scientific reports 31 29670169
2020 Critical role of EphA3 in cancer and current state of EphA3 drug therapeutics. Molecular biology reports 30 32621117
2007 The Hek outer membrane protein of Escherichia coli is an auto-aggregating adhesin and invasin. FEMS microbiology letters 30 17241243
2020 ZnO Quantum Dots Induced Oxidative Stress and Apoptosis in HeLa and HEK-293T Cell Lines. Frontiers in pharmacology 29 32180717
2016 EphA3 as a target for antibody immunotherapy in acute lymphoblastic leukemia. Leukemia 29 27922598
2011 Copy number variations of EphA3 are associated with multiple types of hematologic malignancies. Clinical lymphoma, myeloma & leukemia 29 21454190
2022 Endogenous ion channels expressed in human embryonic kidney (HEK-293) cells. Pflugers Archiv : European journal of physiology 28 35567642
2018 EphA3 Pay-Loaded Antibody Therapeutics for the Treatment of Glioblastoma. Cancers 28 30562956
2017 Transcriptome analysis reveals dynamic changes in coxsackievirus A16 infected HEK 293T cells. BMC genomics 28 28198671
2019 Characterization of influenza H1N1 Gag virus-like particles and extracellular vesicles co-produced in HEK-293SF. Vaccine 27 31358407
2009 Regulation of process retraction and cell migration by EphA3 is mediated by the adaptor protein Nck1. Biochemistry 26 19505147
2009 The time course of Akt and ERK activation on XIAP expression in HEK 293 cell line. Molecular biology reports 24 19649722
2016 Chelerythrine chloride induces apoptosis in renal cancer HEK-293 and SW-839 cell lines. Oncology letters 23 27313717
2015 Transcriptional and post-transcriptional limitations of high-yielding, PEI-mediated transient transfection with CHO and HEK-293E cells. Biotechnology progress 22 25683738
2012 EPHA3 as a novel therapeutic target in the hematological malignancies. Expert review of hematology 22 22780212
2023 Effect of trans-sodium crocetinate on contrast-induced cytotoxicity in HEK-293 cells. Iranian journal of basic medical sciences 21 36742140
2010 EphA3 functions are regulated by collaborating phosphotyrosine residues. Cell research 21 20697431
2023 Peptide ligands for the affinity purification of adeno-associated viruses from HEK 293 cell lysates. Biotechnology and bioengineering 20 37435968
2023 LRRK2 Knockout Confers Resistance in HEK-293 Cells to Rotenone-Induced Oxidative Stress, Mitochondrial Damage, and Apoptosis. International journal of molecular sciences 20 37445652
2022 Production of Lentiviral Vectors Using a HEK-293 Producer Cell Line and Advanced Perfusion Processing. Frontiers in bioengineering and biotechnology 20 35774066
2018 Rapid Isolation of the Mitoribosome from HEK Cells. Journal of visualized experiments : JoVE 20 30346389
2014 EphA3, induced by PC-1/PrLZ, contributes to the malignant progression of prostate cancer. Oncology reports 20 25231727
2010 Biotin regulates the expression of holocarboxylase synthetase in the miR-539 pathway in HEK-293 cells. The Journal of nutrition 20 20592104
2006 Transcriptional profiling of batch and fed-batch protein-free 293-HEK cultures. Metabolic engineering 20 17097906
2021 Antibody-mediated depletion of CCR10+EphA3+ cells ameliorates fibrosis in IPF. JCI insight 19 33945505
2003 EphA3 null mutants do not demonstrate motor axon guidance defects. Molecular and cellular biology 19 14585969
2019 EPHA3 enhances macrophage autophagy and apoptosis by disrupting the mTOR signaling pathway in mice with endometriosis. Bioscience reports 18 31262977
2019 Mitochondrial mRNA fragments are circularized in a human HEK cell line. Mitochondrion 18 31821898
2024 EphA3-targeted chimeric antigen receptor T cells are effective in glioma and generate curative memory T cell responses. Journal for immunotherapy of cancer 17 39111833
2018 EphA3 contributes to tumor growth and angiogenesis in human gastric cancer cells. Oncology reports 17 30066881
2016 EphA3 promotes malignant transformation of colorectal epithelial cells by upregulating oncogenic pathways. Cancer letters 17 27721017
2013 A high-content cellular senescence screen identifies candidate tumor suppressors, including EPHA3. Cell cycle (Georgetown, Tex.) 17 23324396
2018 MiR-340 suppresses the metastasis by targeting EphA3 in cervical cancer. Cell biology international 16 29660208
2017 Epha3 acts as proangiogenic factor in multiple myeloma. Oncotarget 16 28415715
2021 EPHA3 Contributes to Epigenetic Suppression of PTEN in Radioresistant Head and Neck Cancer. Biomolecules 15 33919657
2021 Signaling profiles in HEK 293T cells co-expressing GLP-1 and GIP receptors. Acta pharmacologica Sinica 15 34446852
2015 Antitumor Effects of Oncolytic Adenovirus-Carrying siRNA Targeting Potential Oncogene EphA3. PloS one 15 25978371
1998 IL-1 beta alters the expression of the receptor tyrosine kinase gene r-EphA3 in neonatal rat cardiomyocytes. The American journal of physiology 15 9458884
2024 EphA3 CAR T cells are effective against glioblastoma in preclinical models. Journal for immunotherapy of cancer 14 39111832
2020 Designing and evaluation of MERS-CoV siRNAs in HEK-293 cell line. Journal of infection and public health 14 33493920
2019 Presenilin/γ-secretase-dependent EphA3 processing mediates axon elongation through non-muscle myosin IIA. eLife 14 31577226
2014 Hypoxia-controlled EphA3 marks a human endometrium-derived multipotent mesenchymal stromal cell that supports vascular growth. PloS one 14 25420155
2008 TRP-2 expression protects HEK cells from dopamine- and hydroquinone-induced toxicity. Free radical biology & medicine 14 18674612
2022 Apolipoprotein L1 (APOL1) cation current in HEK-293 cells and in human podocytes. Pflugers Archiv : European journal of physiology 13 36449077
2018 Androgen receptor induces EPHA3 expression by interacting with transcription factor SP1. Oncology reports 13 29917167
2018 EphA3 inhibits migration and invasion of esophageal cancer cells by activating the mesenchymal‑epithelial transition process. International journal of oncology 13 30483759
2009 Infection kinetics of human adenovirus serotype 41 in HEK 293 cells. Memorias do Instituto Oswaldo Cruz 13 19820835
2007 JWA gene is involved in cadmium-induced growth inhibition and apoptosis in HEK-293T cells. Journal of toxicology and environmental health. Part A 13 17479408
2018 EphA3 maintains radioresistance in head and neck cancers through epithelial mesenchymal transition. Cellular signalling 12 29653204
2017 EphA3 targeting reduces in vitro adhesion and invasion and in vivo growth and angiogenesis of multiple myeloma cells. Cellular oncology (Dordrecht, Netherlands) 12 28721629
2011 Reporter gene HEK 293 cells and WNT/Frizzled fusion proteins as tools to study WNT signaling pathways. Biological chemistry 12 21864196
2015 The putative tumor suppressor gene EphA3 fails to demonstrate a crucial role in murine lung tumorigenesis or morphogenesis. Disease models & mechanisms 11 25713296
2014 A high affinity recombinant antibody to the human EphA3 receptor with enhanced ADCC activity. Growth factors (Chur, Switzerland) 11 25413948
2000 Graded expression of EphA3 in the retina and ephrin-A2 in the superior colliculus during initial development of coarse topography in the wallaby retinocollicular projection. The European journal of neuroscience 11 11029633
2023 Circular RNA EPHA3 suppresses progression and metastasis in prostate cancer through the miR-513a-3p/BMP2 axis. Journal of translational medicine 10 37118847
2023 The Ephrin tyrosine kinase a3 (EphA3) is a novel mediator of RAGE-prompted motility of breast cancer cells. Journal of experimental & clinical cancer research : CR 10 37434266
2023 Inhibition of EphA3 Expression in Tumour Stromal Cells Suppresses Tumour Growth and Progression. Cancers 10 37760615
2022 Thapsigargin blocks electromagnetic field-elicited intracellular Ca2+ increase in HEK 293 cells. Physiological reports 10 35510320
2020 Sam68 Promotes the Progression of Human Breast Cancer through inducing Activation of EphA3. Current cancer drug targets 10 31433759
2017 Investigation of the role of tyrosine kinase receptor EPHA3 in colorectal cancer. Scientific reports 10 28169277
2017 Expression and Purification of Protein Complexes Suitable for Structural Studies Using Mammalian HEK 293F Cells. Current protocols in protein science 10 29091272
1994 Localization of a human receptor tyrosine kinase (ETK1) to chromosome region 3p11.2. Genomics 9 8188238

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