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Gene Review

EFNB2  -  ephrin-B2

Homo sapiens

Synonyms: EPH-related receptor tyrosine kinase ligand 5, EPLG5, Ephrin-B2, HTK ligand, HTK-L, ...
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Disease relevance of EFNB2


High impact information on EFNB2

  • The recently characterized crystal structure of the complex formed between the ligand-binding domain of EphB2 and the ectodomain of its binding partner ephrin-B2 provides an insight into the recognition and signal transduction mechanisms of this large multifunctional family of surface receptors [6].
  • A three-day infusion of the ectodomain of either EphB2 or ephrin-B2 into the lateral ventricle disrupted migration of neuroblasts and increased cell proliferation [7].
  • Here, we report that the EphB4 receptor can behave as a tumour suppressor in a mouse xenograft model of breast cancer when stimulated by its ligand, ephrin-B2 [8].
  • These results identify Lerk2 and HtkL as potential determinants of segmental pattern in the peripheral nervous system [9].
  • Interestingly, two cell lines expressing ephrin B2 were not susceptible for rNiV-EGFP, indicating that additional factors are clearly required for full NiV replication [10].

Chemical compound and disease context of EFNB2


Biological context of EFNB2


Anatomical context of EFNB2

  • In transgenic livers, we showed that DLL4, active Notch4, and ephrin B2 were gradually up-regulated within the hepatocarcinoma progression and expressed on tumor sinusoidal endothelial cells [14].
  • Clustered soluble HTKL stimulated the proliferation of sorted HTK+ cord blood cells and a hematopoietic cell line, UT-7/EPO from which HTK was isolated [16].
  • Using RNA fingerprinting, we detected increased expression of Lerk-5 mRNA in human melanocytes as a response to the tumor-promoting drug 12-O-tetradecanoylphorbol-13-acetate, which suggests a possible role of the Lerks in melanoma tumorigenesis and progression [4].
  • Our group has shown that EphB and the ephrin-B subfamilies are coexpressed in human colorectal cancer, and ephrin-B2 is expressed at higher levels in human colorectal cancer than in adjacent normal mucosa [15].
  • Here, we show expression of EphB6 in human thymus, as well as the expression of ephrin-B2 in both human and mouse thymus [17].

Associations of EFNB2 with chemical compounds


Other interactions of EFNB2

  • Ephrin-B1 and ephrin-B2 proteins are predominantly found in the developing plexiform layers, suggesting a role in the development of intraretinal connections [23].
  • Expression profile of EFNB1, EFNB2, two ligands of EPHB2 in human gastric cancer [1].
  • Taken together, these data indicate that the expression of EPHB6, EFNB2, and EFNB3 may serve as prognostic indicators of favorable NBs [24].
  • These findings suggest the involvement of HTK-HTKL system in the proliferation of HTK+ hematopoietic progenitor cells in the hematopoietic environment [16].
  • Moreover, when EphB4 and ephrin-B2 were expressed in neighbouring Swiss 3T3 fibroblasts, VASP and Mena co-accumulated with activated Eph receptors at protrusions formed by EphB4-expressing cells [25].

Analytical, diagnostic and therapeutic context of EFNB2


  1. Expression profile of EFNB1, EFNB2, two ligands of EPHB2 in human gastric cancer. Kataoka, H., Tanaka, M., Kanamori, M., Yoshii, S., Ihara, M., Wang, Y.J., Song, J.P., Li, Z.Y., Arai, H., Otsuki, Y., Kobayashi, T., Konno, H., Hanai, H., Sugimura, H. J. Cancer Res. Clin. Oncol. (2002) [Pubmed]
  2. Prognostic significance of EPHB6, EFNB2, and EFNB3 expressions in neuroblastoma. Tang, X.X., Zhao, H., Robinson, M.E., Cnaan, A., London, W., Cohn, S.L., Cheung, N.K., Brodeur, G.M., Evans, A.E., Ikegaki, N. Med. Pediatr. Oncol. (2000) [Pubmed]
  3. Comparative integromics on Ephrin family. Katoh, Y., Katoh, M. Oncol. Rep. (2006) [Pubmed]
  4. Overexpression of Lerk-5/Eplg5 messenger RNA: a novel marker for increased tumorigenicity and metastatic potential in human malignant melanomas. Vogt, T., Stolz, W., Welsh, J., Jung, B., Kerbel, R.S., Kobayashi, H., Landthaler, M., McClelland, M. Clin. Cancer Res. (1998) [Pubmed]
  5. Activation of the receptor EphB4 by its specific ligand ephrin B2 in human osteoarthritic subchondral bone osteoblasts. Kwan Tat, S., Pelletier, J.P., Amiable, N., Boileau, C., Lajeunesse, D., Duval, N., Martel-Pelletier, J. Arthritis Rheum. (2008) [Pubmed]
  6. Ephs and ephrins close ranks. Cutforth, T., Harrison, C.J. Trends Neurosci. (2002) [Pubmed]
  7. Disruption of Eph/ephrin signaling affects migration and proliferation in the adult subventricular zone. Conover, J.C., Doetsch, F., Garcia-Verdugo, J.M., Gale, N.W., Yancopoulos, G.D., Alvarez-Buylla, A. Nat. Neurosci. (2000) [Pubmed]
  8. The EphB4 receptor suppresses breast cancer cell tumorigenicity through an Abl-Crk pathway. Noren, N.K., Foos, G., Hauser, C.A., Pasquale, E.B. Nat. Cell Biol. (2006) [Pubmed]
  9. Eph family transmembrane ligands can mediate repulsive guidance of trunk neural crest migration and motor axon outgrowth. Wang, H.U., Anderson, D.J. Neuron (1997) [Pubmed]
  10. Establishment of a Nipah virus rescue system. Yoneda, M., Guillaume, V., Ikeda, F., Sakuma, Y., Sato, H., Wild, T.F., Kai, C. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  11. Expression of receptor tyrosine kinase HTK (hepatoma transmembrane kinase) and HTK ligand by human leukemia-lymphoma cell lines. Steube, K.G., Meyer, C., Habig, S., Uphoff, C.C., Drexler, H.G. Leuk. Lymphoma (1999) [Pubmed]
  12. Ephrin-B2 induces migration of endothelial cells through the phosphatidylinositol-3 kinase pathway and promotes angiogenesis in adult vasculature. Maekawa, H., Oike, Y., Kanda, S., Ito, Y., Yamada, Y., Kurihara, H., Nagai, R., Suda, T. Arterioscler. Thromb. Vasc. Biol. (2003) [Pubmed]
  13. Ephrin-B2 ligand is a functional receptor for Hendra virus and Nipah virus. Bonaparte, M.I., Dimitrov, A.S., Bossart, K.N., Crameri, G., Mungall, B.A., Bishop, K.A., Choudhry, V., Dimitrov, D.S., Wang, L.F., Eaton, B.T., Broder, C.C. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  14. The Role of the Vascular Endothelial Growth Factor-Delta-like 4 Ligand/Notch4-Ephrin B2 Cascade in Tumor Vessel Remodeling and Endothelial Cell Functions. Hainaud, P., Contrerès, J.O., Villemain, A., Liu, L.X., Plouët, J., Tobelem, G., Dupuy, E. Cancer Res. (2006) [Pubmed]
  15. Effects of overexpression of ephrin-B2 on tumour growth in human colorectal cancer. Liu, W., Jung, Y.D., Ahmad, S.A., McCarty, M.F., Stoeltzing, O., Reinmuth, N., Fan, F., Ellis, L.M. Br. J. Cancer (2004) [Pubmed]
  16. Characterization of a ligand for receptor protein-tyrosine kinase HTK expressed in immature hematopoietic cells. Sakano, S., Serizawa, R., Inada, T., Iwama, A., Itoh, A., Kato, C., Shimizu, Y., Shinkai, F., Shimizu, R., Kondo, S., Ohno, M., Suda, T. Oncogene (1996) [Pubmed]
  17. Ephrin-B2 is a candidate ligand for the Eph receptor, EphB6. Munthe, E., Rian, E., Holien, T., Rasmussen, A., Levy, F.O., Aasheim, H. FEBS Lett. (2000) [Pubmed]
  18. Coexpression of ephrin-Bs and their receptors in colon carcinoma. Liu, W., Ahmad, S.A., Jung, Y.D., Reinmuth, N., Fan, F., Bucana, C.D., Ellis, L.M. Cancer (2002) [Pubmed]
  19. Specification of distinct dopaminergic neural pathways: roles of the Eph family receptor EphB1 and ligand ephrin-B2. Yue, Y., Widmer, D.A., Halladay, A.K., Cerretti, D.P., Wagner, G.C., Dreyer, J.L., Zhou, R. J. Neurosci. (1999) [Pubmed]
  20. Biphasic functions of the kinase-defective Ephb6 receptor in cell adhesion and migration. Matsuoka, H., Obama, H., Kelly, M.L., Matsui, T., Nakamoto, M. J. Biol. Chem. (2005) [Pubmed]
  21. Cell-type specific and estrogen dependent expression of the receptor tyrosine kinase EphB4 and its ligand ephrin-B2 during mammary gland morphogenesis. Nikolova, Z., Djonov, V., Zuercher, G., Andres, A.C., Ziemiecki, A. J. Cell. Sci. (1998) [Pubmed]
  22. Engineered fibrin matrices for functional display of cell membrane-bound growth factor-like activities: study of angiogenic signaling by ephrin-B2. Zisch, A.H., Zeisberger, S.M., Ehrbar, M., Djonov, V., Weber, C.C., Ziemiecki, A., Pasquale, E.B., Hubbell, J.A. Biomaterials (2004) [Pubmed]
  23. Graded and lamina-specific distributions of ligands of EphB receptor tyrosine kinases in the developing retinotectal system. Braisted, J.E., McLaughlin, T., Wang, H.U., Friedman, G.C., Anderson, D.J., O'leary, D.D. Dev. Biol. (1997) [Pubmed]
  24. Association among EPHB2, TrkA, and MYCN expression in low-stage neuroblastomas. Tang, X.X., Evans, A.E., Zhao, H., Cnaan, A., Brodeur, G.M., Ikegaki, N. Med. Pediatr. Oncol. (2001) [Pubmed]
  25. Ena/VASP proteins mediate repulsion from ephrin ligands. Evans, I.R., Renne, T., Gertler, F.B., Nobes, C.D. J. Cell. Sci. (2007) [Pubmed]
  26. Ephrin-B2 is differentially expressed in the intestinal epithelium in Crohn's disease and contributes to accelerated epithelial wound healing in vitro. Hafner, C., Meyer, S., Langmann, T., Schmitz, G., Bataille, F., Hagen, I., Becker, B., Roesch, A., Rogler, G., Landthaler, M., Vogt, T. World J. Gastroenterol. (2005) [Pubmed]
  27. Assignments of the GAS6, POSTN and EFNB2 genes to SSC11 by somatic cell and radiation hybrid panels. Ma, H., Liu, X., Shi, Q., He, C., Yerle, M., Ren, H., Li, K. Anim. Genet. (2005) [Pubmed]
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