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Gene Review

Efnb1  -  ephrin B1

Mus musculus

Synonyms: CEK5 receptor ligand, CEK5-L, Cek5 ligand, Cek5-L, EFL-3, ...
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Disease relevance of Efnb1


High impact information on Efnb1

  • We conclude that in the intestinal epithelium beta-catenin and TCF couple proliferation and differentiation to the sorting of cell populations through the EphB/ephrin-B system [3].
  • Moreover, Lerk2 is an in vivo substrate for the platelet-derived growth factor receptor, which suggests crosstalk between Lerk2 signaling and signaling cascades activated by tyrosine kinases [4].
  • Complete ablation of ephrin-B1 resulted in perinatal lethality associated with a range of phenotypes, including defects in neural crest cell (NCC)-derived tissues, incomplete body wall closure, and abnormal skeletal patterning [5].
  • To understand the role of ephrin-B1 and the importance of ephrin-B1-induced reverse signaling during embryonic development, we have generated mouse lines carrying mutations in the efnb1 gene [5].
  • To explore how ephrins could provide positional labels for cell targeting, we tested whether endogenous endothelial and P19 cell EphB1 (ELK) and EphB2 (Nuk) receptors discriminate between different oligomeric forms of an ephrin-B1/Fc fusion ligand [6].

Biological context of Efnb1

  • In addition, we show that Efnb1/Efnb2 double heterozygous embryos exhibit phenotypes in a number of NCC derivatives [7].
  • Ephrin-B1 reverse signaling activates JNK through a novel mechanism that is independent of tyrosine phosphorylation [8].
  • We report here that transfection of ephrin-B1 into 293 cells resulted in robust increase in JNK activity, whereas expression of truncated ephrin-B1 lacking the cytoplasmic domain had a negligible effect, indicating that the induction of JNK activity was attributed mainly to the reverse signaling [8].
  • Genomic organization and chromosomal localization of mouse Eplg2, a gene encoding a binding protein for the receptor tyrosine kinase elk [9].
  • The Eplg2 genomic locus spans a region of approximately 12 kb, encoding five exons and four introns [9].

Anatomical context of Efnb1

  • Here, we use DiI (1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate) labeling to assess the pathfinding of commissural axons in the spinal cords of ephrin-B and EphB mutant mouse embryos [10].
  • Similarly, Elk-L is expressed in hindbrain segments, the roof plate, and floor plate, which overlaps with that of other transmembrane ligands, but has distinct expression in somites [11].
  • Lac z Histochemistry and immunohistochemistry reveal ephrin-B ligand expression in the inner ear [12].
  • Here we reported the expression of ephrin-B1 and its cognate EphB receptors in the adult mouse hippocampus at 3, 7, 15, 30 and 60 days after transections of the entorhinal afferents [13].
  • EphB receptor tyrosine kinases and ephrin-B ligands regulate several types of cell-cell interactions during brain development, generally by modulating the cytoskeleton [14].

Associations of Efnb1 with chemical compounds

  • Surprisingly, ephrin-B1 that lacked all six intracellular tyrosine residues still triggered JNK activation and rounding morphology of the transfected cells [8].
  • Ephrin-B1 transduces signals to activate integrin-mediated migration, attachment and angiogenesis [15].
  • Human DEC (differentially expressed in chondrocytes), mouse STRA (stimulated with retinoic acid), and rat SHARP (split and hairy related protein) proteins constitute a new and structurally distinct class of the basic helix-loop-helix proteins [16].
  • By contrast, ephrin-B1 was detected in tubules throughout the whole nephron [17].
  • We investigated the mobilizing effect of a combined cyclophosphamide (CTX) and granulocyte colony-stimulating factor (G-CSF) treatment on progenitor cells (STRA) and primitive stem cells (LTRA) in normal and splenectomized CBA/H mice [18].

Physical interactions of Efnb1

  • By using a series of deletion and domain substitution mutants, we now report that an N-terminal globular domain of the Nuk/Cek5 receptor is the ligand binding domain of the transmembrane ligand Lerk2 [19].
  • 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 [20].

Regulatory relationships of Efnb1

  • Interestingly, treatment of COS cells and B35 neuronal-like cells with ephrin-B1 to activate endogenous EphB2 decreased the kinase activity of endogenous Abl [21].

Other interactions of Efnb1

  • We also report the sequence and expression pattern in mouse embryos and adult tissues of one of these novel RA-inducible genes, Stra1, and show that it corresponds to the mouse ligand for the Cek5 receptor protein-tyrosine kinase [1].
  • EphB receptors and their ephrin-B ligands are required for midline guidance decisions at several rostrocaudal levels of the developing CNS [10].
  • Eplg2 was mapped to the mouse X chromosome by interspecific backcross analysis and is tightly linked to the androgen receptor (Ar) locus [9].
  • Consistent with these observations, activation of JNK and the resulting morphological changes mediated by ephrin-B1 could be abolished by the JNK inhibitor SP600125 but not the Src inhibitor PP2 [8].
  • Vax2 mutants also exhibit flattened DV and NT gradients of the EphA5, EphB2, EphB3, ephrin-B1 and ephrin-B2 axon guidance cues [22].

Analytical, diagnostic and therapeutic context of Efnb1

  • Using reverse transcription-polymerase chain reaction (RT-PCR), Western blot and immunocytochemical analyses, we identified distinct and reciprocal expression patterns of full-length isoforms of EphA5, EphA6, EphA7, EphB1, ephrin-A2 and ephrin-B1 that correlated with structural features of the peripheral vestibular system in adult rats [23].
  • We have detected substantial levels of the EphB2 and EphB6 receptors and the ephrin-B1 ligand in the adult mouse kidney by RT-PCR amplification [17].


  1. Efficient cloning of cDNAs of retinoic acid-responsive genes in P19 embryonal carcinoma cells and characterization of a novel mouse gene, Stra1 (mouse LERK-2/Eplg2). Bouillet, P., Oulad-Abdelghani, M., Vicaire, S., Garnier, J.M., Schuhbaur, B., Dollé, P., Chambon, P. Dev. Biol. (1995) [Pubmed]
  2. Distribution of EphB receptors and ephrin-B1 in the developing vertebrate spinal cord. Jevince, A.R., Kadison, S.R., Pittman, A.J., Chien, C.B., Kaprielian, Z. J. Comp. Neurol. (2006) [Pubmed]
  3. Beta-catenin and TCF mediate cell positioning in the intestinal epithelium by controlling the expression of EphB/ephrinB. Batlle, E., Henderson, J.T., Beghtel, H., van den Born, M.M., Sancho, E., Huls, G., Meeldijk, J., Robertson, J., van de Wetering, M., Pawson, T., Clevers, H. Cell (2002) [Pubmed]
  4. Tyrosine phosphorylation of transmembrane ligands for Eph receptors. Brückner, K., Pasquale, E.B., Klein, R. Science (1997) [Pubmed]
  5. Ephrin-B1 forward and reverse signaling are required during mouse development. Davy, A., Aubin, J., Soriano, P. Genes Dev. (2004) [Pubmed]
  6. Eph receptors discriminate specific ligand oligomers to determine alternative signaling complexes, attachment, and assembly responses. Stein, E., Lane, A.A., Cerretti, D.P., Schoecklmann, H.O., Schroff, A.D., Van Etten, R.L., Daniel, T.O. Genes Dev. (1998) [Pubmed]
  7. Ephrin-B2 forward signaling regulates somite patterning and neural crest cell development. Davy, A., Soriano, P. Dev. Biol. (2007) [Pubmed]
  8. Ephrin-B1 reverse signaling activates JNK through a novel mechanism that is independent of tyrosine phosphorylation. Xu, Z., Lai, K.O., Zhou, H.M., Lin, S.C., Ip, N.Y. J. Biol. Chem. (2003) [Pubmed]
  9. Genomic organization and chromosomal localization of mouse Eplg2, a gene encoding a binding protein for the receptor tyrosine kinase elk. Fletcher, F.A., Renshaw, B., Hollingsworth, T., Baum, P., Lyman, S.D., Jenkins, N.A., Gilbert, D.J., Copeland, N.G., Davison, B.L. Genomics (1994) [Pubmed]
  10. EphB receptors and ephrin-B3 regulate axon guidance at the ventral midline of the embryonic mouse spinal cord. Kadison, S.R., Mäkinen, T., Klein, R., Henkemeyer, M., Kaprielian, Z. J. Neurosci. (2006) [Pubmed]
  11. Distinct and overlapping expression patterns of ligands for Eph-related receptor tyrosine kinases during mouse embryogenesis. Flenniken, A.M., Gale, N.W., Yancopoulos, G.D., Wilkinson, D.G. Dev. Biol. (1996) [Pubmed]
  12. 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]
  13. Induction of ephrin-B1 and EphB receptors during denervation-induced plasticity in the adult mouse hippocampus. Wang, Y., Ying, G.X., Liu, X., Wang, W.Y., Dong, J.H., Ni, Z.M., Zhou, C.F. Eur. J. Neurosci. (2005) [Pubmed]
  14. EphB receptor tyrosine kinases control morphological development of the ventral midbrain. Altick, A.L., Dravis, C., Bowdler, T., Henkemeyer, M., Mastick, G.S. Mech. Dev. (2005) [Pubmed]
  15. Ephrin-B1 transduces signals to activate integrin-mediated migration, attachment and angiogenesis. Huynh-Do, U., Vindis, C., Liu, H., Cerretti, D.P., McGrew, J.T., Enriquez, M., Chen, J., Daniel, T.O. J. Cell. Sci. (2002) [Pubmed]
  16. DEC1 negatively regulates the expression of DEC2 through binding to the E-box in the proximal promoter. Li, Y., Xie, M., Song, X., Gragen, S., Sachdeva, K., Wan, Y., Yan, B. J. Biol. Chem. (2003) [Pubmed]
  17. EphB2 and ephrin-B1 expressed in the adult kidney regulate the cytoarchitecture of medullary tubule cells through Rho family GTPases. Ogawa, K., Wada, H., Okada, N., Harada, I., Nakajima, T., Pasquale, E.B., Tsuyama, S. J. Cell. Sci. (2006) [Pubmed]
  18. Peripheral blood stem cells differ from bone marrow stem cells in cell cycle status, repopulating potential, and sensitivity toward hyperthermic purging in mice mobilized with cyclophosphamide and granulocyte colony-stimulating factor. Wierenga, P.K., Setroikromo, R., Kamps, G., Kampinga, H.H., Vellenga, E. J. Hematother. Stem Cell Res. (2002) [Pubmed]
  19. The N-terminal globular domain of Eph receptors is sufficient for ligand binding and receptor signaling. Labrador, J.P., Brambilla, R., Klein, R. EMBO J. (1997) [Pubmed]
  20. 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]
  21. Multiple signaling interactions of Abl and Arg kinases with the EphB2 receptor. Yu, H.H., Zisch, A.H., Dodelet, V.C., Pasquale, E.B. Oncogene (2001) [Pubmed]
  22. 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]
  23. Distinct expression patterns of eph receptors and ephrins relate to the structural organization of the adult rat peripheral vestibular system. Matsunaga, T., Greene, M.I., Davis, J.G. Eur. J. Neurosci. (2000) [Pubmed]
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