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Gene Review

Efnb2  -  ephrin B2

Mus musculus

Synonyms: ELF-2, EPH-related receptor tyrosine kinase ligand 5, Elf2, Ephrin-B2, Epl5, ...
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Disease relevance of Efnb2


High impact information on Efnb2


Chemical compound and disease context of Efnb2


Biological context of Efnb2

  • In addition, we show that Efnb1/Efnb2 double heterozygous embryos exhibit phenotypes in a number of NCC derivatives [10].
  • Expression of one copy of a mutant version of Efnb2 that lacks tyrosine phosphorylation sites was sufficient to rescue the embryonic phenotypes associated with loss of Efnb2 [10].
  • Our results uncover an important role for ephrin-B2 in NCC and somites during embryogenesis and suggest that ephrin-B2 exerts many of its embryonic function via activation of forward signaling [10].
  • We now show that cell surface molecules essential for proper axon pathfinding in the developing nervous system, namely ephrin-B2 and the ephrin receptors EphB2 and EphB3, also play major roles in cell adhesion events that tubularize the urethra and partition the urinary and alimentary tracts [11].
  • Therefore, we addressed the question of whether ephrin-B2 signaling modulates MM cell migration and matrix interaction [3].

Anatomical context of Efnb2


Associations of Efnb2 with chemical compounds

  • In db/db mice at the normoalbuminuric stage, hypoxia-inducible factor-1alpha (HIF-1alpha), ephrin B2, glomerular epithelial protein 1, and Pod-1, which play key roles in glomerulogenesis, were already upregulated in parallel with an alteration of genes related to glucose metabolism, lipid metabolism, and oxidative stress [8].
  • The list of differentially expressed genes includes genes involved in cell growth, differentiation, adhesion, proteolysis, as well as signaling molecules of receptors for growth factors, integrin, Ephrin B2, endothelin, and adhesion G protein coupled receptor [15].
  • In a chemotaxis assay, the PI3 kinase-specific inhibitor LY294002 blocked the migratory response of HUVECs induced by addition of ephrin-B2/Fc [9].

Physical interactions of Efnb2

  • The main structural difference between ephrin-B1 and ephrin-B2 is the conformation of the receptor-binding G-H loop and the partially disordered N-terminal tetramerization region of ephrin-B1 [16].

Regulatory relationships of Efnb2

  • Ephrin-B2 is expressed at the mouse chiasm midline as the ipsilateral projection is generated and is selectively inhibitory to axons from ventrotemporal (VT) retina, where ipsilaterally projecting RGCs reside [17].

Other interactions of Efnb2

  • ELF-2, a new member of the Eph ligand family, is segmentally expressed in mouse embryos in the region of the hindbrain and newly forming somites [12].
  • Vax2 mutants also exhibit flattened DV and NT gradients of the EphA5, EphB2, EphB3, ephrin-B1 and ephrin-B2 axon guidance cues [18].
  • In the lateral wall, EphA4, ephrin-A3 and ephrin-B2 were strongly expressed, while ephrin-A3 was particularly strongly expressed in utricular and saccular sensory epithelia [19].
  • Cells transfected with the paxillin mutant Y31F/Y118F displayed a reduced migration in response to ephrin B2 stimulation [20].
  • The expression of other members of this gene family, including ephrin-B2, EphA2, and ephrin-A1, in a compartmentalized pattern within the Purkinje cell layer suggests a possible redundancy and/or a compensation of EphA4 function in the segmental patterning of cerebellar Purkinje cells [21].

Analytical, diagnostic and therapeutic context of Efnb2


  1. Interplay between EphB4 on tumor cells and vascular ephrin-B2 regulates tumor growth. Noren, N.K., Lu, M., Freeman, A.L., Koolpe, M., Pasquale, E.B. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  2. Regulation of vasculogenesis and angiogenesis by EphB/ephrin-B2 signaling between endothelial cells and surrounding mesenchymal cells. Oike, Y., Ito, Y., Hamada, K., Zhang, X.Q., Miyata, K., Arai, F., Inada, T., Araki, K., Nakagata, N., Takeya, M., Kisanuki, Y.Y., Yanagisawa, M., Gale, N.W., Suda, T. Blood (2002) [Pubmed]
  3. Ephrin-B2 overexpression enhances integrin-mediated ECM-attachment and migration of B16 melanoma cells. Meyer, S., Hafner, C., Guba, M., Flegel, S., Geissler, E.K., Becker, B., Koehl, G.E., Orsó, E., Landthaler, M., Vogt, T. Int. J. Oncol. (2005) [Pubmed]
  4. Expression of EphA4 in developing inner ears of the mouse and guinea pig. van Heumen, W.R., Claxton, C., Pickles, J.O. Hear. Res. (2000) [Pubmed]
  5. Ephrin-B2 controls cell motility and adhesion during blood-vessel-wall assembly. Foo, S.S., Turner, C.J., Adams, S., Compagni, A., Aubyn, D., Kogata, N., Lindblom, P., Shani, M., Zicha, D., Adams, R.H. Cell (2006) [Pubmed]
  6. Arteriovenous malformations in mice lacking activin receptor-like kinase-1. Urness, L.D., Sorensen, L.K., Li, D.Y. Nat. Genet. (2000) [Pubmed]
  7. Symmetrical mutant phenotypes of the receptor EphB4 and its specific transmembrane ligand ephrin-B2 in cardiovascular development. Gerety, S.S., Wang, H.U., Chen, Z.F., Anderson, D.J. Mol. Cell (1999) [Pubmed]
  8. Altered Gene Expression Related to Glomerulogenesis and Podocyte Structure in Early Diabetic Nephropathy of db/db Mice and Its Restoration by Pioglitazone. Makino, H., Miyamoto, Y., Sawai, K., Mori, K., Mukoyama, M., Nakao, K., Yoshimasa, Y., Suga, S. Diabetes (2006) [Pubmed]
  9. 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]
  10. Ephrin-B2 forward signaling regulates somite patterning and neural crest cell development. Davy, A., Soriano, P. Dev. Biol. (2007) [Pubmed]
  11. Bidirectional signaling mediated by ephrin-B2 and EphB2 controls urorectal development. Dravis, C., Yokoyama, N., Chumley, M.J., Cowan, C.A., Silvany, R.E., Shay, J., Baker, L.A., Henkemeyer, M. Dev. Biol. (2004) [Pubmed]
  12. ELF-2, a new member of the Eph ligand family, is segmentally expressed in mouse embryos in the region of the hindbrain and newly forming somites. Bergemann, A.D., Cheng, H.J., Brambilla, R., Klein, R., Flanagan, J.G. Mol. Cell. Biol. (1995) [Pubmed]
  13. Lac z Histochemistry and immunohistochemistry reveal ephrin-B ligand expression in the inner ear. Bianchi, L.M., Dinsio, K., Davoli, K., Gale, N.W. J. Histochem. Cytochem. (2002) [Pubmed]
  14. Ephrin-B2 reverse signaling is required for axon pathfinding and cardiac valve formation but not early vascular development. Cowan, C.A., Yokoyama, N., Saxena, A., Chumley, M.J., Silvany, R.E., Baker, L.A., Srivastava, D., Henkemeyer, M. Dev. Biol. (2004) [Pubmed]
  15. Global gene expression analysis in the bones reveals involvement of several novel genes and pathways in mediating an anabolic response of mechanical loading in mice. Xing, W., Baylink, D., Kesavan, C., Hu, Y., Kapoor, S., Chadwick, R.B., Mohan, S. J. Cell. Biochem. (2005) [Pubmed]
  16. Crystal structure of the ephrin-B1 ectodomain: implications for receptor recognition and signaling. Nikolov, D.B., Li, C., Barton, W.A., Himanen, J.P. Biochemistry (2005) [Pubmed]
  17. Ephrin-B2 and EphB1 mediate retinal axon divergence at the optic chiasm. Williams, S.E., Mann, F., Erskine, L., Sakurai, T., Wei, S., Rossi, D.J., Gale, N.W., Holt, C.E., Mason, C.A., Henkemeyer, M. Neuron (2003) [Pubmed]
  18. The homeodomain protein Vax2 patterns the dorsoventral and nasotemporal axes of the eye. Mui, S.H., Hindges, R., O'Leary, D.D., Lemke, G., Bertuzzi, S. Development (2002) [Pubmed]
  19. Expression of Ephs and ephrins in developing mouse inner ear. Pickles, J.O. Hear. Res. (2003) [Pubmed]
  20. EphB1-mediated cell migration requires the phosphorylation of paxillin at Tyr-31/Tyr-118. Vindis, C., Teli, T., Cerretti, D.P., Turner, C.E., Huynh-Do, U. J. Biol. Chem. (2004) [Pubmed]
  21. EphA4 is not required for Purkinje cell compartmentation. Karam, S.D., Dottori, M., Ogawa, K., Henderson, J.T., Boyd, A.W., Pasquale, E.B., Bothwell, M. Brain Res. Dev. Brain Res. (2002) [Pubmed]
  22. 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]
  23. Purification, crystallization and preliminary characterization of an Eph-B2/ephrin-B2 complex. Himanen, J.P., Nikolov, D.B. Acta Crystallogr. D Biol. Crystallogr. (2002) [Pubmed]
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