Skip to main content

EphA3, Erythropoietin-Producing Hepatocellular Carcinoma Cell Receptor A3

  • Reference work entry
Book cover Encyclopedia of Signaling Molecules
  • 58 Accesses

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Institutional subscriptions

References

  • Bae HJ, Song JH, Noh JH, Kim JK, Jung KH, Eun JW, et al. Low frequency mutation of the Ephrin receptor A3 gene in hepatocellular carcinoma. Neoplasma. 2009;56:331–4.

    Article  PubMed  CAS  Google Scholar 

  • Balakrishnan A, Bleeker FE, Lamba S, Rodolfo M, Daniotti M, Scarpa A, et al. Novel somatic and germline mutations in cancer candidate genes in glioblastoma, melanoma, and pancreatic carcinoma. Cancer Res. 2007;67:3545–50.

    Article  PubMed  CAS  Google Scholar 

  • Beckmann MP, Cerretti DP, 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  CAS  Google Scholar 

  • Boyd AW, Ward LD, Wicks IP, Simpson RJ, Salvaris E, Wilks A, et al. Isolation and characterization of a novel receptor-type protein tyrosine kinase (hek) from a human pre-B cell line. J Biol Chem. 1992;267:3262–7.

    PubMed  CAS  Google Scholar 

  • Brantley-Sieders DM, Caughron J, Hicks D, Pozzi A, Ruiz JC, Chen J. EphA2 receptor tyrosine kinase regulates endothelial cell migration and vascular assembly through phosphoinositide 3-kinase-mediated Rac1 GTPase activation. J Cell Sci. 2004;117:2037–49.

    Article  PubMed  CAS  Google Scholar 

  • Brown A, Yates PA, Burrola P, Ortuno D, Vaidya A, Jessell TM, 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.

    Article  PubMed  CAS  Google Scholar 

  • Carim-Todd L, Bath KG, Fulgenzi G, Yanpallewar S, Jing D, Barrick CA, et al. Endogenous truncated TrkB.T1 receptor regulates neuronal complexity and TrkB kinase receptor function in vivo. J Neurosci. 2009;29:678–85.

    Article  PubMed  CAS  Google Scholar 

  • Carvalho RF, Beutler M, Marler KJ, Knoll B, Becker-Barroso E, Heintzmann R, et al. Silencing of EphA3 through a cis interaction with ephrinA5. Nat Neurosci. 2006;9:322–30.

    Article  PubMed  CAS  Google Scholar 

  • Cerretti DP, Vanden Bos T, Nelson N, Kozlosky CJ, Reddy P, Maraskovsky E, et al. Isolation of LERK-5: a ligand of the eph-related receptor tyrosine kinases. Mol Immunol. 1995;32:1197–205.

    Article  PubMed  CAS  Google Scholar 

  • Cheng HJ, Flanagan JG. Identification and cloning of ELF-1, a developmentally expressed ligand for the Mek4 and Sek receptor tyrosine kinases. Cell. 1994;79:157–68.

    Article  PubMed  CAS  Google Scholar 

  • Cheng HJ, Nakamoto M, Bergemann AD, Flanagan JG. Complementary gradients in expression and binding of ELF-1 and Mek4 in development of the topographic retinotectal projection map. Cell. 1995;82:371–81.

    Article  PubMed  CAS  Google Scholar 

  • Chiari R, Hames G, Stroobant V, Texier C, Maillere B, Boon T, et al. Identification of a tumor-specific shared antigen derived from an Eph receptor and presented to CD4 T cells on HLA class II molecules. Cancer Res. 2000;60:4855–63.

    PubMed  CAS  Google Scholar 

  • Ciossek T, Monschau B, Kremoser C, Loschinger J, Lang S, Muller BK, et al. Eph receptor-ligand interactions are necessary for guidance of retinal ganglion cell axons in vitro. Eur J Neurosci. 1998;10:1574–80.

    Article  PubMed  CAS  Google Scholar 

  • Cooper MA, Son AI, Komlos D, Sun Y, Kleiman NJ, Zhou R. Loss of ephrin-A5 function disrupts lens fiber cell packing and leads to cataract. Proc Natl Acad Sci USA. 2008;105:16620–5.

    Article  PubMed  CAS  Google Scholar 

  • Corbo V, Ritelli R, Barbi S, Funel N, Campani D, Bardelli A, et al. Mutational profiling of kinases in human tumours of pancreatic origin identifies candidate cancer genes in ductal and ampulla of vater carcinomas. PLoS One. 2010;5:e12653.

    Article  PubMed  CAS  Google Scholar 

  • Davis TL, Walker JR, Loppnau P, Butler-Cole C, Allali-Hassani A, Dhe-Paganon S. Autoregulation by the juxtamembrane region of the human ephrin receptor tyrosine kinase A3 (EphA3). Structure. 2008;16:873–84.

    Article  PubMed  CAS  Google Scholar 

  • Day B, To C, Himanen JP, Smith FM, Nikolov DB, Boyd AW, et al. Three distinct molecular surfaces in ephrin-A5 are essential for a functional interaction with EphA3. J Biol Chem. 2005;280:26526–32.

    Article  PubMed  CAS  Google Scholar 

  • Demyanenko GP, Siesser PF, Wright AG, Brennaman LH, Bartsch U, Schachner M, et al. L1 and CHL1 cooperate in thalamocortical axon targeting. Cereb Cortex. 2011;21:401–12.

    Article  PubMed  Google Scholar 

  • Ding L, Getz G, Wheeler DA, Mardis ER, McLellan MD, Cibulskis K, et al. Somatic mutations affect key pathways in lung adenocarcinoma. Nature. 2008;455:1069–75.

    Article  PubMed  CAS  Google Scholar 

  • Drescher U, Kremoser C, Handwerker C, Loschinger J, Noda M, Bonhoeffer F. In vitro guidance of retinal ganglion cell axons by RAGS, a 25 kDa tectal protein related to ligands for Eph receptor tyrosine kinases. Cell. 1995;82:359–70.

    Article  PubMed  CAS  Google Scholar 

  • Dufour A, Seibt J, Passante L, Depaepe V, Ciossek T, Frisen J, et al. Area specificity and topography of thalamocortical projections are controlled by ephrin/Eph genes. Neuron. 2003;39:453–65.

    Article  PubMed  CAS  Google Scholar 

  • Feldheim DA, Kim YI, Bergemann AD, Frisen J, Barbacid M, Flanagan JG. Genetic analysis of ephrin-A2 and ephrin-A5 shows their requirement in multiple aspects of retinocollicular mapping. Neuron. 2000;25:563–74.

    Article  PubMed  CAS  Google Scholar 

  • Feldheim DA, Nakamoto M, Osterfield M, Gale NW, DeChiara TM, Rohatgi R, et al. Loss-of-function analysis of EphA receptors in retinotectal mapping. J Neurosci. 2004;24:2542–50.

    Article  PubMed  CAS  Google Scholar 

  • Frieden LA, Townsend TA, Vaught DB, Delaughter DM, Hwang Y, Barnett JV, et al. Regulation of heart valve morphogenesis by Eph receptor ligand, ephrin-A1. Dev Dyn. 2010;239:3226–34.

    Article  PubMed  CAS  Google Scholar 

  • Gallarda BW, Bonanomi D, Muller D, Brown A, Alaynick WA, Andrews SE, et al. Segregation of axial motor and sensory pathways via heterotypic trans-axonal signaling. Science (New York NY). 2008;320:233–6.

    Article  CAS  Google Scholar 

  • Himanen JP, Nikolov DB. Eph signaling: a structural view. Trends Neurosci. 2003;26:46–51.

    Article  PubMed  CAS  Google Scholar 

  • Himanen JP, Rajashankar KR, Lackmann M, Cowan CA, Henkemeyer M, Nikolov DB. Crystal structure of an Eph receptor-ephrin complex. Nature. 2001;414:933–8.

    Article  PubMed  CAS  Google Scholar 

  • Holzman LB, Marks RM, Dixit VM. A novel immediate-early response gene of endothelium is induced by cytokines and encodes a secreted protein. Mol Cell Biol. 1990;10:5830–8.

    PubMed  CAS  Google Scholar 

  • Hu T, Shi G, Larose L, Rivera GM, Mayer BJ, Zhou R. Regulation of process retraction and cell migration by EphA3 is mediated by the adaptor protein Nck1. Biochemistry. 2009;48:6369–78.

    Article  PubMed  CAS  Google Scholar 

  • Iwamasa H, Ohta K, Yamada T, Ushijima K, Terasaki H, Tanaka H. Expression of Eph receptor tyrosine kinases and their ligands in chick embryonic motor neurons and hindlimb muscles. Dev Growth Differ. 1999;41:685–98.

    Article  PubMed  CAS  Google Scholar 

  • Janes PW, Saha N, Barton WA, Kolev MV, Wimmer-Kleikamp SH, 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.

    Article  PubMed  CAS  Google Scholar 

  • Kilpatrick TJ, Brown A, Lai C, Gassmann M, Goulding M, Lemke G. Expression of the Tyro4/Mek4/Cek4 gene specifically marks a subset of embryonic motor neurons and their muscle targets. Mol Cell Neurosci. 1996;7:62–74.

    Article  PubMed  CAS  Google Scholar 

  • Kozlosky CJ, Maraskovsky E, McGrew JT, VandenBos T, Teepe M, Lyman SD, et al. Ligands for the receptor tyrosine kinases hek and elk: isolation of cDNAs encoding a family of proteins. Oncogene. 1995;10:299–306.

    PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • Labrador JP, 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.

    Article  PubMed  CAS  Google Scholar 

  • Lackmann M, Bucci T, Mann RJ, Kravets LA, Viney E, Smith F, et al. Purification of a ligand for the EPH-like receptor HEK using a biosensor-based affinity detection approach. Proc Natl Acad Sci USA. 1996;93:2523–7.

    Article  PubMed  CAS  Google Scholar 

  • Lackmann M, Mann RJ, Kravets L, Smith FM, Bucci TA, Maxwell KF, 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.

    Article  PubMed  CAS  Google Scholar 

  • Lackmann M, Oates AC, Dottori M, Smith FM, 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.

    Article  PubMed  CAS  Google Scholar 

  • Lai C, Lemke G. An extended family of protein-tyrosine kinase genes differentially expressed in the vertebrate nervous system. Neuron. 1991;6:691–704.

    Article  PubMed  CAS  Google Scholar 

  • Lawrenson ID, Wimmer-Kleikamp SH, Lock P, Schoenwaelder SM, Down M, Boyd AW, et al. Ephrin-A5 induces rounding, blebbing and de-adhesion of EphA3-expressing 293 T and melanoma cells by CrkII and Rho-mediated signalling. J Cell Sci. 2002;115:1059–72.

    PubMed  CAS  Google Scholar 

  • Lee DJ, Schonleben F, Banuchi VE, Qiu W, Close LG, Assaad AM, et al. Multiple tumor-suppressor genes on chromosome 3p contribute to head and neck squamous cell carcinoma tumorigenesis. Cancer Biol Ther. 2010;10:689–93.

    Article  PubMed  CAS  Google Scholar 

  • Li YY, McTiernan CF, Feldman AM. 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  CAS  Google Scholar 

  • Li W, Fan J, Woodley DT. Nck/Dock: an adapter between cell surface receptors and the actin cytoskeleton. Oncogene. 2001;20:6403–17.

    Article  PubMed  CAS  Google Scholar 

  • Mackarehtschian K, Lau CK, Caras I, McConnell SK. Regional differences in the developing cerebral cortex revealed by ephrin-A5 expression. Cereb Cortex. 1999;9:601–10.

    Article  PubMed  CAS  Google Scholar 

  • Nievergall E, Janes PW, Stegmayer C, Vail ME, Haj FG, Teng SW, et al. PTP1B regulates Eph receptor function and trafficking. J Cell Biol. 2010;191:1189–203.

    Article  PubMed  CAS  Google Scholar 

  • Pabbisetty KB, Yue X, Li C, Himanen JP, Zhou R, Nikolov DB, 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.

    Article  PubMed  CAS  Google Scholar 

  • Pasquale EB. Eph-ephrin bidirectional signaling in physiology and disease. Cell. 2008;133:38–52.

    Article  PubMed  CAS  Google Scholar 

  • Passante L, Gaspard N, Degraeve M, Frisen J, Kullander K, De Maertelaer V, et al. Temporal regulation of ephrin/Eph signalling is required for the spatial patterning of the mammalian striatum. Development(Cambridge, England). 2008;135:3281–90.

    Article  CAS  Google Scholar 

  • Sajjadi FG, Pasquale EB, 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  CAS  Google Scholar 

  • Schulte D, Cepko CL. Two homeobox genes define the domain of EphA3 expression in the developing chick retina. Development (Cambridge, England). 2000;127:5033–45.

    CAS  Google Scholar 

  • Sharfe N, Freywald A, Toro A, Roifman CM. Ephrin-A1 induces c-Cbl phosphorylation and EphA receptor down-regulation in T cells. J Immunol. 2003;170:6024–32.

    PubMed  CAS  Google Scholar 

  • Shi G, Yue G, Zhou R. EphA3 functions are regulated by collaborating phosphotyrosine residues. Cell Res. 2010;20:1263–75.

    Article  PubMed  CAS  Google Scholar 

  • Sieber BA, Kuzmin A, Canals JM, Danielsson A, Paratcha G, Arenas E, et al. Disruption of EphA/ephrin-a signaling in the nigrostriatal system reduces dopaminergic innervation and dissociates behavioral responses to amphetamine and cocaine. Mol Cell Neurosci. 2004;26:418–28.

    Article  PubMed  CAS  Google Scholar 

  • Smith FM, Vearing C, Lackmann M, Treutlein H, Himanen J, Chen K, et al. Dissecting the EphA3/Ephrin-A5 interactions using a novel functional mutagenesis screen. J Biol Chem. 2004a;279:9522–31.

    Article  PubMed  CAS  Google Scholar 

  • Smith LM, Walsh PT, Rudiger T, Cotter TG, Mc Carthy TV, Marx A, et al. EphA3 is induced by CD28 and IGF-1 and regulates cell adhesion. Exp Cell Res. 2004b;292:295–303.

    Article  PubMed  CAS  Google Scholar 

  • Stein E, Lane AA, Cerretti DP, Schoecklmann HO, Schroff AD, Van Etten RL, et al. Eph receptors discriminate specific ligand oligomers to determine alternative signaling complexes, attachment, and assembly responses. Genes Dev. 1998;12:667–78.

    Article  PubMed  CAS  Google Scholar 

  • Stephen LJ, Fawkes AL, Verhoeve A, Lemke G, Brown A. A critical role for the EphA3 receptor tyrosine kinase in heart development. Dev Biol. 2007;302:66–79.

    Article  PubMed  CAS  Google Scholar 

  • Stubbs J, Palmer A, Vidovic M, Marotte LR. 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. Eur J Neurosci. 2000;12:3626–36.

    Article  PubMed  CAS  Google Scholar 

  • Takahashi H, Shintani T, Sakuta H, Noda M. CBF1 controls the retinotectal topographical map along the anteroposterior axis through multiple mechanisms. Development (Cambridge, England). 2003;130:5203–15.

    Article  CAS  Google Scholar 

  • Takahashi H, Sakuta H, Shintani T, Noda M. Functional mode of FoxD1/CBF2 for the establishment of temporal retinal specificity in the developing chick retina. Dev Biol. 2009;331:300–10.

    Article  PubMed  CAS  Google Scholar 

  • Uziel D, Muhlfriedel S, Zarbalis K, Wurst W, Levitt P, Bolz J. Miswiring of limbic thalamocortical projections in the absence of ephrin-A5. J Neurosci. 2002;22:9352–7.

    PubMed  CAS  Google Scholar 

  • Uziel D, Garcez P, Lent R, Peuckert C, Niehage R, Weth F, et al. Connecting thalamus and cortex: the role of ephrins. Anat Rec. 2006;288:135–42.

    Article  CAS  Google Scholar 

  • Vearing CJ, Lackmann M. Eph receptor signalling; dimerisation just isn’t enough. Growth factors (Chur, Switzerland). 2005;23:67–76.

    Article  CAS  Google Scholar 

  • Vearing C, Lee FT, Wimmer-Kleikamp S, Spirkoska V, To C, Stylianou C, et al. Concurrent binding of anti-EphA3 antibody and ephrin-A5 amplifies EphA3 signaling and downstream responses: potential as EphA3-specific tumor-targeting reagents. Cancer Res. 2005;65:6745–54.

    Article  PubMed  CAS  Google Scholar 

  • Wicks IP, Wilkinson D, Salvaris E, Boyd AW. Molecular cloning of HEK, the gene encoding a receptor tyrosine kinase expressed by human lymphoid tumor cell lines. Proc Natl Acad Sci USA. 1992;89:1611–5.

    Article  PubMed  CAS  Google Scholar 

  • Wimmer-Kleikamp SH, 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.

    Article  PubMed  CAS  Google Scholar 

  • Winslow JW, Moran P, Valverde J, Shih A, Yuan JQ, Wong SC, et al. Cloning of AL-1, a ligand for an Eph-related tyrosine kinase receptor involved in axon bundle formation. Neuron. 1995;14:973–81.

    Article  PubMed  CAS  Google Scholar 

  • Wood LD, Calhoun ES, Silliman N, Ptak J, Szabo S, Powell SM, et al. Somatic mutations of GUCY2F, EPHA3, and NTRK3 in human cancers. Hum Mutat. 2006;27:1060–1.

    Article  PubMed  Google Scholar 

  • Yue Y, Widmer DA, Halladay AK, Cerretti DP, Wagner GC, Dreyer JL, et al. Specification of distinct dopaminergic neural pathways: roles of the Eph family receptor EphB1 and ligand ephrin-B2. J Neurosci. 1999;19:2090–101.

    PubMed  CAS  Google Scholar 

  • Yue Y, Chen ZY, Gale NW, Blair-Flynn J, Hu TJ, Yue X, et al. Mistargeting hippocampal axons by expression of a truncated Eph receptor. Proc Natl Acad Sci USA. 2002;99:10777–82.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Renping Zhou .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2012 Springer Science+Business Media, LLC

About this entry

Cite this entry

Zhou, R. (2012). EphA3, Erythropoietin-Producing Hepatocellular Carcinoma Cell Receptor A3. In: Choi, S. (eds) Encyclopedia of Signaling Molecules. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-0461-4_628

Download citation

Publish with us

Policies and ethics