epha3 receptor


Summary: An eph family receptor that is found primarily in adult BRAIN and variety of tissues in the developing embryo tissues. During embryonic development high levels of EphA3 receptor expression is seen in the nervous system and coincides with neuronal cell migration, suggesting a role for this protein in axonal pathfinding.

Top Publications

  1. Hu T, Shi G, Larose L, Rivera G, Mayer B, Zhou R. Regulation of process retraction and cell migration by EphA3 is mediated by the adaptor protein Nck1. Biochemistry. 2009;48:6369-78 pubmed publisher
    ..mediated through binding of the Nck1 SH2 domain to the phosphotyrosine residue at position 602 (Y602) of the EphA3 receptor. The removal of the SH2 domain or the mutation of the Y602 residue abolishes the interaction...
  2. Cobb J, Duboule D. Comparative analysis of genes downstream of the Hoxd cluster in developing digits and external genitalia. Development. 2005;132:3055-67 pubmed
    ..e. the digits and the penis/clitoris. ..
  3. Lackmann M, Mann R, Kravets L, Smith F, Bucci T, Maxwell K, et al. Ligand for EPH-related kinase (LERK) 7 is the preferred high affinity ligand for the HEK receptor. J Biol Chem. 1997;272:16521-30 pubmed
    ..By extrapolation, our findings indicate that some of the reported LERK-receptor interactions are a consequence of the use of bivalent ligand or receptor constructs and may be functionally irrelevant. ..
  4. Stephen L, Fawkes A, Verhoeve A, Lemke G, Brown A. A critical role for the EphA3 receptor tyrosine kinase in heart development. Dev Biol. 2007;302:66-79 pubmed
    ..We now describe a critical role for EphA3 receptor signaling in heart development as revealed by the phenotype of EphA3 null mice...
  5. Lackmann M, Oates A, Dottori M, Smith F, Do C, Power M, et al. Distinct subdomains of the EphA3 receptor mediate ligand binding and receptor dimerization. J Biol Chem. 1998;273:20228-37 pubmed
    ..Based on exon structure we have dissected the extracellular region of EphA3 receptor into evolutionarily conserved subdomains and used kinetic BIAcore analysis, mRNA injection into zebrafish ..
  6. Hattori M, Osterfield M, Flanagan J. Regulated cleavage of a contact-mediated axon repellent. Science. 2000;289:1360-5 pubmed
    ..These studies reveal mechanisms for protease recognition and control of cell surface proteins, and, for ephrin-A2, they may provide a means for efficient axon detachment and termination of signaling. ..
  7. Clifford N, Smith L, Powell J, Gattenlohner S, Marx A, O Connor R. The EphA3 receptor is expressed in a subset of rhabdomyosarcoma cell lines and suppresses cell adhesion and migration. J Cell Biochem. 2008;105:1250-9 pubmed publisher
    ..These data indicate that EphA3 expression may define subsets of RMS tumours, and that EphA3 suppresses motility through regulation of Rho GTPases in RMS cells. ..
  8. Brown A, Yates P, Burrola P, Ortuno D, Vaidya A, Jessell T, et al. Topographic mapping from the retina to the midbrain is controlled by relative but not absolute levels of EphA receptor signaling. Cell. 2000;102:77-88 pubmed
    ..We find that these two populations form separate maps in the colliculus, which can be predicted as a function of the net EphA receptor level that a given ganglion cell expresses relative to its neighbors. ..
  9. Wicks I, Wilkinson D, Salvaris E, Boyd A. Molecular cloning of HEK, the gene encoding a receptor tyrosine kinase expressed by human lymphoid tumor cell lines. Proc Natl Acad Sci U S A. 1992;89:1611-5 pubmed
    ..5- to 6.0-kb HEK transcripts in LK63 and the T-cell lines JM and HSB-2. Southern blot analysis of DNA from LK63 suggested that the HEK gene was neither amplified nor rearranged in the LK63 tumor. ..

More Information


  1. Beckmann M, Cerretti D, Baum P, Vanden Bos T, James L, Farrah T, et al. Molecular characterization of a family of ligands for eph-related tyrosine kinase receptors. EMBO J. 1994;13:3757-62 pubmed
    ..Since these two ligand sequences are similar, and since elk and hek are members of a larger family of eph-related receptor molecules, we refer to these ligands as LERKs (ligands for eph-related kinases). ..
  2. Wimmer Kleikamp S, Nievergall E, Gegenbauer K, Adikari S, Mansour M, Yeadon T, et al. Elevated protein tyrosine phosphatase activity provokes Eph/ephrin-facilitated adhesion of pre-B leukemia cells. Blood. 2008;112:721-32 pubmed publisher
  3. Das S, Lin J, Papamatheakis J, Sykulev Y, Tsichlis P. Differential splicing generates Tvl-1/RFXANK isoforms with different functions. J Biol Chem. 2002;277:45172-80 pubmed
    ..Since both Tvl-L and Tvl-S are identical in their ability to induce the expression of EphA3, we conclude that Tvl-1 regulates the expression of non-MHC genes by RFX-independent mechanisms. ..
  4. Otal R, Burgaya F, Frisen J, Soriano E, Martinez A. Ephrin-A5 modulates the topographic mapping and connectivity of commissural axons in murine hippocampus. Neuroscience. 2006;141:109-21 pubmed
    ..Immunocytochemical analyses revealed prominent expression of the EphA3 receptor, a putative receptor for ephrin-A5, in the main cells and the neuropil of the developing hippocampus...
  5. Janes P, Saha N, Barton W, Kolev M, Wimmer Kleikamp S, Nievergall E, et al. Adam meets Eph: an ADAM substrate recognition module acts as a molecular switch for ephrin cleavage in trans. Cell. 2005;123:291-304 pubmed
    ..Our data suggest a simple mechanism for regulating ADAM10-mediated ephrin proteolysis, which ensures that only Eph bound ephrins are recognized and cleaved. ..
  6. Wimmer Kleikamp S, Janes P, Squire A, Bastiaens P, Lackmann M. Recruitment of Eph receptors into signaling clusters does not require ephrin contact. J Cell Biol. 2004;164:661-6 pubmed
  7. Ivanov A, Steiner A, Scheck A, Romanovsky A. Expression of Eph receptors and their ligands, ephrins, during lipopolysaccharide fever in rats. Physiol Genomics. 2005;21:152-60 pubmed
  8. Xu B, Li S, Brown A, Gerlai R, Fahnestock M, Racine R. EphA/ephrin-A interactions regulate epileptogenesis and activity-dependent axonal sprouting in adult rats. Mol Cell Neurosci. 2003;24:984-99 pubmed
    ..Our results suggest that EphA receptors and ephrin-A ligands modify neuronal plasticity and may serve as spatial cues that modulate the development and pattern of activation-dependent axonal growth in adult CNS. ..
  9. Smith L, Walsh P, Rudiger T, Cotter T, Mc Carthy T, Marx A, et al. EphA3 is induced by CD28 and IGF-1 and regulates cell adhesion. Exp Cell Res. 2004;292:295-303 pubmed
    ..The data suggest that CD28- and IGF-1-regulated expression of EphA3 is associated with adherence and that it may be involved in the motility of malignant T cells. ..
  10. Day B, To C, Himanen J, Smith F, Nikolov D, Boyd A, et al. Three distinct molecular surfaces in ephrin-A5 are essential for a functional interaction with EphA3. J Biol Chem. 2005;280:26526-32 pubmed
  11. Mancia F, Shapiro L. ADAM and Eph: how Ephrin-signaling cells become detached. Cell. 2005;123:185-7 pubmed
    ..In this issue of Cell, Janes et al. (2005) show that the ephrin ligand can be proteolytically released from its membrane tether by a complex on the opposing cell composed of the ephrin receptor and an ADAM metalloprotease. ..
  12. Pabbisetty K, Yue X, Li C, Himanen J, Zhou R, Nikolov D, et al. Kinetic analysis of the binding of monomeric and dimeric ephrins to Eph receptors: correlation to function in a growth cone collapse assay. Protein Sci. 2007;16:355-61 pubmed
    ..Our kinetic analysis and correlation of binding affinity with function helped us better understand the interactions between ephrins and Eph receptors and should be useful in the design of inhibitors that interfere with the interactions. ..
  13. Murai K, Pasquale E. Neuroscience. Axons seek neighborly advice. Science. 2008;320:185-6 pubmed publisher
  14. Gallarda B, Bonanomi D, Muller D, Brown A, Alaynick W, Andrews S, et al. Segregation of axial motor and sensory pathways via heterotypic trans-axonal signaling. Science. 2008;320:233-6 pubmed publisher
    ..Effective assembly of a key circuit underlying motor behaviors thus critically depends on trans-axonal signaling interactions resolving motor and sensory projections into discrete pathways. ..
  15. Carvalho R, Beutler M, Marler K, Knöll B, Becker Barroso E, Heintzmann R, et al. Silencing of EphA3 through a cis interaction with ephrinA5. Nat Neurosci. 2006;9:322-30 pubmed
    ..Our data suggest that formation of this complex transforms the uniform expression of EphAs in the nasal part of the retina into a gradient of functional EphAs and has a key role in controlling retinotectal mapping. ..
  16. Pickles J, van Heumen W. The expression of messenger RNAs coding for growth factors, their receptors, and eph-class receptor tyrosine kinases in normal and ototoxically damaged chick cochleae. Dev Neurosci. 1997;19:476-87 pubmed
    ..The eph-class receptor tyrosine kinase CEK10 may be involved in cell interactions in the cochlear sensory epithelium, while CEK4 and CEK8 may play a role in the cochlear innervation. ..
  17. Ajioka I, Nakajima K. Birth-date-dependent segregation of the mouse cerebral cortical neurons in reaggregation cultures. Eur J Neurosci. 2005;22:331-42 pubmed
    ..These findings suggest that cortical neurons acquire a birth-date-dependent segregation mechanism before their somas reach the MZ. ..
  18. Yun M, Johnson R, Antic A, Donoghue M. EphA family gene expression in the developing mouse neocortex: regional patterns reveal intrinsic programs and extrinsic influence. J Comp Neurol. 2003;456:203-16 pubmed
  19. Eszlinger M, Krohn K, Paschke R. Complementary DNA expression array analysis suggests a lower expression of signal transduction proteins and receptors in cold and hot thyroid nodules. J Clin Endocrinol Metab. 2001;86:4834-42 pubmed
  20. Durbin L, Brennan C, Shiomi K, Cooke J, Barrios A, Shanmugalingam S, et al. Eph signaling is required for segmentation and differentiation of the somites. Genes Dev. 1998;12:3096-109 pubmed
    ..We suggest that Eph signaling has a key role in the translation of the patterning of presomitic mesoderm into somites. ..
  21. Pfeiffenberger C, Cutforth T, Woods G, Yamada J, RENTERIA R, Copenhagen D, et al. Ephrin-As and neural activity are required for eye-specific patterning during retinogeniculate mapping. Nat Neurosci. 2005;8:1022-7 pubmed
    ..Thus, ephrin-As and neural activity act together to control patterning of eye-specific retinogeniculate layers. ..
  22. Kudo C, Ajioka I, Hirata Y, Nakajima K. Expression profiles of EphA3 at both the RNA and protein level in the developing mammalian forebrain. J Comp Neurol. 2005;487:255-69 pubmed
  23. Yue Y, Su J, Cerretti D, Fox G, Jing S, Zhou R. Selective inhibition of spinal cord neurite outgrowth and cell survival by the Eph family ligand ephrin-A5. J Neurosci. 1999;19:10026-35 pubmed
  24. Kao H, Chen H, Wu C, Lin W. Tyrosine-kinase expression profiles in human gastric cancer cell lines and their modulations with retinoic acids. Br J Cancer. 2003;88:1058-64 pubmed
    ..In the present study, we demonstrate an efficient and simple RAGE approach for examining tyrosine kinases' expression in tumour cells and their alterations following drug treatments. ..
  25. Bardelli A, Parsons D, Silliman N, Ptak J, Szabo S, Saha S, et al. Mutational analysis of the tyrosine kinome in colorectal cancers. Science. 2003;300:949 pubmed
  26. Jayasena C, Flood W, Koblar S. High EphA3 expressing ophthalmic trigeminal sensory axons are sensitive to ephrin-A5-Fc: implications for lobe specific axon guidance. Neuroscience. 2005;135:97-109 pubmed
    ..The implication of these results is that EphA3 forward signaling in ophthalmic sensory axons may be an important mechanism in vivo for lobe specific guidance of trigeminal ganglion ophthalmic projections. ..
  27. Triplett J, Owens M, Yamada J, Lemke G, Cang J, Stryker M, et al. Retinal input instructs alignment of visual topographic maps. Cell. 2009;139:175-85 pubmed publisher
    ..These data suggest a general model in which convergent maps use coincident activity patterns to achieve alignment. ..
  28. Aasheim H, Terstappen L, Logtenberg T. Regulated expression of the Eph-related receptor tyrosine kinase Hek11 in early human B lymphopoiesis. Blood. 1997;90:3613-22 pubmed
  29. Sharfe N, Freywald A, Toro A, Roifman C. Ephrin-A1 induces c-Cbl phosphorylation and EphA receptor down-regulation in T cells. J Immunol. 2003;170:6024-32 pubmed
  30. Li Y, McTiernan C, Feldman A. IL-1 beta alters the expression of the receptor tyrosine kinase gene r-EphA3 in neonatal rat cardiomyocytes. Am J Physiol. 1998;274:H331-41 pubmed
    ..In the adult rat, r-EphA3 transcripts were most abundant in the heart, brain, and lung. These results suggest that IL-1 beta may exert its effect on cardiac myocytes at least in part by altering r-EphA3 expression. ..
  31. Himanen J, Chumley M, Lackmann M, Li C, Barton W, Jeffrey P, et al. Repelling class discrimination: ephrin-A5 binds to and activates EphB2 receptor signaling. Nat Neurosci. 2004;7:501-9 pubmed
    ..The structural data reveal the molecular basis for EphB2-ephrin-A5 signaling and provide a framework for understanding the complexities of functional interactions and crosstalk between A- and B-subclass Eph receptors and ephrins. ..
  32. Scully A, McKeown M, Thomas J. Isolation and characterization of Dek, a Drosophila eph receptor protein tyrosine kinase. Mol Cell Neurosci. 1999;13:337-47 pubmed
    ..Dek is also expressed by photoreceptor cells of third-instar larvae as they project axons into the optic brain lobe. Misexpression and overexpression of full-length Dek or kinase-inactive Dek do not grossly affect axon pathfinding. ..
  33. Nishida K, Flanagan J, Nakamoto M. Domain-specific olivocerebellar projection regulated by the EphA-ephrin-A interaction. Development. 2002;129:5647-58 pubmed
    ..Conversely, overexpression of a truncated EphA3 receptor in the cerebellum reduces endogenous ligand activity to undetectable levels and causes aberrant mapping, with ..
  34. Labrador J, Brambilla R, Klein R. The N-terminal globular domain of Eph receptors is sufficient for ligand binding and receptor signaling. EMBO J. 1997;16:3889-97 pubmed
    ..Our studies have determined the first structural elements involved in ligand-receptor interaction and will allow more fine-tuned genetic experiments to elucidate the mechanism of action of these important guidance molecules. ..
  35. Feldheim D, Nakamoto M, Osterfield M, Gale N, DeChiara T, Rohatgi R, et al. Loss-of-function analysis of EphA receptors in retinotectal mapping. J Neurosci. 2004;24:2542-50 pubmed
    ..Expressing patches of a cytoplasmically truncated EphA3 receptor in chick retina caused temporal axons to have reduced responsiveness to posterior tectal repellent activity in ..
  36. Wicks I, Lapsys N, Baker E, Campbell L, Boyd A, Sutherland G. Localization of a human receptor tyrosine kinase (ETK1) to chromosome region 3p11.2. Genomics. 1994;19:38-41 pubmed
    ..2. Karyotype analysis of the cell lines that over-express hek showed no cytogenetically visible abnormality involving the hek locus. ..
  37. Fox G, Holst P, Chute H, Lindberg R, Janssen A, Basu R, et al. cDNA cloning and tissue distribution of five human EPH-like receptor protein-tyrosine kinases. Oncogene. 1995;10:897-905 pubmed
    ..Analysis of these new EPH sub-family members will increase our understanding of the biology of this receptor family and their isolation will provide reagents for the identification of ligands for this large family of orphan receptors. ..
  38. Koulakov A, Tsigankov D. A stochastic model for retinocollicular map development. BMC Neurosci. 2004;5:30 pubmed
    ..including bifurcation in heterozygous Isl2/EphA3 knock-ins. The model is based on known chemical labels, axonal repulsion/competition, and stochasticity. Possible mapping in Isl2/EphB knock-ins is also discussed. ..
  39. Shintani T, Sakuta H, Noda M. [Molecular mechanisms for the formation of topographic retinotectal projection]. Brain Nerve. 2008;60:425-35 pubmed
    ..We show that Ptpro controls the sensitivity of retinal axons to ephrins, and thereby plays crucial roles in the topographic projection. ..
  40. Ting M, Day B, Spanevello M, Boyd A. Activation of ephrin A proteins influences hematopoietic stem cell adhesion and trafficking patterns. Exp Hematol. 2010;38:1087-98 pubmed publisher
  41. Kawakami Y, Uchiyama Y, Rodriguez Esteban C, Inenaga T, Koyano Nakagawa N, Kawakami H, et al. Sall genes regulate region-specific morphogenesis in the mouse limb by modulating Hox activities. Development. 2009;136:585-94 pubmed publisher
  42. Huberman A, Murray K, Warland D, Feldheim D, Chapman B. Ephrin-As mediate targeting of eye-specific projections to the lateral geniculate nucleus. Nat Neurosci. 2005;8:1013-21 pubmed
  43. Schulte D, Peters M, Sen J, Cepko C. The rod photoreceptor pattern is set at the optic vesicle stage and requires spatially restricted cVax expression. J Neurosci. 2005;25:2823-31 pubmed
    ..This pattern therefore appears to be specified by an activity acting before, or in parallel with, these factors. In contrast, misexpression of the ventrally restricted transcription factor, cVax, severely disturbed the rod pattern. ..
  44. Rodger J, Vitale P, Tee L, King C, Bartlett C, Fall A, et al. EphA/ephrin-A interactions during optic nerve regeneration: restoration of topography and regulation of ephrin-A2 expression. Mol Cell Neurosci. 2004;25:56-68 pubmed
    ..The findings, supported by in vitro studies, implicate EphA/ephrin-A interactions in restoring precise topography and in regulating ephrin-A2 expression during regeneration. ..
  45. Vaidya A, Pniak A, Lemke G, Brown A. EphA3 null mutants do not demonstrate motor axon guidance defects. Mol Cell Biol. 2003;23:8092-8 pubmed
    ..Our results also demonstrate that ephrin A5's ability to direct topographic innervation of the acromiotrapezius must be mediated through EphA receptors other than, or in addition to, EphA3. ..
  46. Böhme B, Holtrich U, Wolf G, Luzius H, Grzeschik K, Strebhardt K, et al. PCR mediated detection of a new human receptor-tyrosine-kinase, HEK 2. Oncogene. 1993;8:2857-62 pubmed
    ..In a protein kinase assay with HEK 2-specific immunoprecipitates from the human epidermoid carcinoma cell line A431, a protein of 130 kDa was found phosphorylated. ..
  47. Sajjadi F, Pasquale E, Subramani S. Identification of a new eph-related receptor tyrosine kinase gene from mouse and chicken that is developmentally regulated and encodes at least two forms of the receptor. New Biol. 1991;3:769-78 pubmed
    ..However, a shorter transcript was found to be expressed at reduced levels in the testis. This new Eph-related receptor may play an important role during development and in signal transduction pathways. ..