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EFNB1  -  ephrin-B1

Homo sapiens

Synonyms: CFND, CFNS, EFB1, EFL-3, EFL3, ...
 
 
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Disease relevance of EFNB1

 

High impact information on EFNB1

 

Chemical compound and disease context of EFNB1

  • Moreover, endogenous ARMS protein is tyrosine phosphorylated after neurotrophin treatment of pheochromocytoma 12 cells and primary hippocampal neurons or ephrin B treatment of NG108-15 cells, demonstrating that ARMS is a downstream target for both neurotrophin and ephrin receptors [11].
 

Biological context of EFNB1

  • Here, we show that the classical female CFNS phenotype is caused by heterozygous loss-of-function mutations in EFNB1, which encodes a member of the ephrin family of transmembrane ligands for Eph receptor tyrosine kinases [12].
  • Although EFNB1 is X-inactivated, we did not observe markedly skewed X-inactivation in either blood or cranial periosteum from females with CFNS, indicating that lack of ephrin-B1 does not compromise cell viability in these tissues [12].
  • Recently, we have mapped a gene for CFNS in the pericentromeric region of the X chromosome that contains the EFNB1 gene, which encodes the ephrin-B1 ligand for Eph receptors [13].
  • In the two other families, missense mutations in EFNB1 were detected that lead to amino acid exchanges P54L and T111I [13].
  • Comparative genomics analyses on EFNB1, EFNB2 and EFNB3 were performed by using bioinformatics and human intelligence (humint) [14].
 

Anatomical context of EFNB1

 

Associations of EFNB1 with chemical compounds

  • Moreover, in EFNB1-treated fetal thymus organ culture, CD117(+), CD25(+), DP, CD4 SP, and CD8 SP cells all had significantly enhanced proliferation history, according to bromodeoxyuridine uptake [18].
  • We propose that in heterozygous females, patchwork loss of ephrin-B1 disturbs tissue boundary formation at the developing coronal suture, whereas in males deficient in ephrin-B1, an alternative mechanism maintains the normal boundary [12].
  • These findings suggest that ephrin B1-expressing granulosa cells can directly interact with Eph-bearing cells during corpus luteum formation in vivo, suggesting that Eph-ephrin system is involved in this process [19].
  • Interactions between these molecules are promiscuous, but largely fall into two groups: EphA receptors bind to glycosylphosphatidyl inositol-anchored ephrin-A ligands, and EphB receptors bind to transmembrane ephrin-B proteins [20].
  • Interactions between ephrin-B and metabotropic glutamate 1 receptors in brain tissue and cultured neurons [21].
 

Physical interactions of EFNB1

  • Within the group of LERKs, LERK-2 and -5 were shown to bind to HEK2 [22].
 

Regulatory relationships of EFNB1

  • This interaction could be inhibited by preincubation of HEK2 expressing cells with soluble LERK-2 [22].
  • A dominant-negative mutant of dynamin or potassium depletion blocks ephrin-B1 endocytosis [23].
  • Knockdown of Numb suppressed the ephrin-B1-induced spine development and maturation [24].
  • Our results suggest a novel function of the C-terminus of ephrin-B1 in activating MMP-8 secretion, which promotes the invasion of cancer cells [25].
 

Other interactions of EFNB1

  • Ephrin-B1 and ephrin-B2 proteins are predominantly found in the developing plexiform layers, suggesting a role in the development of intraretinal connections [26].
  • Coexpression of transcripts encoding EPHB receptor protein tyrosine kinases and their ephrin-B ligands in human small cell lung carcinoma [27].
  • CONCLUSIONS: These findings suggest that not only the expression of EPHB2, but the expression of its ligand EFNB1 may have some relation with the oncogenesis of gastric cancer [1].
  • A second mRNA profile that included ephrin-A3, ephrin-A5, and ephrin-B1 was expressed by a subset of tumors [2].
  • Ligands of EPH family receptors are called ephrins, which include ephrin-A and ephrin-B subgroups [28].
 

Analytical, diagnostic and therapeutic context of EFNB1

References

  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. Human osteosarcoma expresses specific ephrin profiles: implications for tumorigenicity and prognosis. Varelias, A., Koblar, S.A., Cowled, P.A., Carter, C.D., Clayer, M. Cancer (2002) [Pubmed]
  3. A novel phenotypic pattern in X-linked inheritance: craniofrontonasal syndrome maps to Xp22. Feldman, G.J., Ward, D.E., Lajeunie-Renier, E., Saavedra, D., Robin, N.H., Proud, V., Robb, L.J., Der Kaloustian, V., Carey, J.C., Cohen, M.M., Cormier, V., Munnich, A., Zackai, E.H., Wilkie, A.O., Price, R.A., Muenke, M. Hum. Mol. Genet. (1997) [Pubmed]
  4. Ephrin-B3 Ligand Promotes Glioma Invasion through Activation of Rac1. Nakada, M., Drake, K.L., Nakada, S., Niska, J.A., Berens, M.E. Cancer Res. (2006) [Pubmed]
  5. Phosphorylation of ephrin-B1 regulates dissemination of gastric scirrhous carcinoma. Tanaka, M., Kamata, R., Takigahira, M., Yanagihara, K., Sakai, R. Am. J. Pathol. (2007) [Pubmed]
  6. Axon guidance: the cytoplasmic tail. Patel, B.N., Van Vactor, D.L. Curr. Opin. Cell Biol. (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. 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]
  9. Tiam1 mediates neurite outgrowth induced by ephrin-B1 and EphA2. Tanaka, M., Ohashi, R., Nakamura, R., Shinmura, K., Kamo, T., Sakai, R., Sugimura, H. EMBO J. (2004) [Pubmed]
  10. Surface densities of ephrin-B1 determine EphB1-coupled activation of cell attachment through alphavbeta3 and alpha5beta1 integrins. Huynh-Do, U., Stein, E., Lane, A.A., Liu, H., Cerretti, D.P., Daniel, T.O. EMBO J. (1999) [Pubmed]
  11. An evolutionarily conserved transmembrane protein that is a novel downstream target of neurotrophin and ephrin receptors. Kong, H., Boulter, J., Weber, J.L., Lai, C., Chao, M.V. J. Neurosci. (2001) [Pubmed]
  12. Mutations of ephrin-B1 (EFNB1), a marker of tissue boundary formation, cause craniofrontonasal syndrome. Twigg, S.R., Kan, R., Babbs, C., Bochukova, E.G., Robertson, S.P., Wall, S.A., Morriss-Kay, G.M., Wilkie, A.O. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  13. Mutations of the ephrin-B1 gene cause craniofrontonasal syndrome. Wieland, I., Jakubiczka, S., Muschke, P., Cohen, M., Thiele, H., Gerlach, K.L., Adams, R.H., Wieacker, P. Am. J. Hum. Genet. (2004) [Pubmed]
  14. Comparative integromics on Ephrin family. Katoh, Y., Katoh, M. Oncol. Rep. (2006) [Pubmed]
  15. The carboxyl terminus of B class ephrins constitutes a PDZ domain binding motif. Lin, D., Gish, G.D., Songyang, Z., Pawson, T. J. Biol. Chem. (1999) [Pubmed]
  16. Downregulation of the Ras-mitogen-activated protein kinase pathway by the EphB2 receptor tyrosine kinase is required for ephrin-induced neurite retraction. Elowe, S., Holland, S.J., Kulkarni, S., Pawson, T. Mol. Cell. Biol. (2001) [Pubmed]
  17. EPHB4 regulates chemokine-evoked trophoblast responses: a mechanism for incorporating the human placenta into the maternal circulation. Red-Horse, K., Kapidzic, M., Zhou, Y., Feng, K.T., Singh, H., Fisher, S.J. Development (2005) [Pubmed]
  18. Ephrin-B1 is critical in T-cell development. Yu, G., Mao, J., Wu, Y., Luo, H., Wu, J. J. Biol. Chem. (2006) [Pubmed]
  19. Ephrin B1 is expressed on human luteinizing granulosa cells in corpora lutea of the early luteal phase: the possible involvement of the B class Eph-ephrin system during corpus luteum formation. Egawa, M., Yoshioka, S., Higuchi, T., Sato, Y., Tatsumi, K., Fujiwara, H., Fujii, S. J. Clin. Endocrinol. Metab. (2003) [Pubmed]
  20. Roles of Eph receptors and ephrins in segmental patterning. Xu, Q., Mellitzer, G., Wilkinson, D.G. Philos. Trans. R. Soc. Lond., B, Biol. Sci. (2000) [Pubmed]
  21. Interactions between ephrin-B and metabotropic glutamate 1 receptors in brain tissue and cultured neurons. Calò, L., Bruno, V., Spinsanti, P., Molinari, G., Korkhov, V., Esposito, Z., Patanè, M., Melchiorri, D., Freissmuth, M., Nicoletti, F. J. Neurosci. (2005) [Pubmed]
  22. Cell-cell adhesion mediated by binding of membrane-anchored ligand LERK-2 to the EPH-related receptor human embryonal kinase 2 promotes tyrosine kinase activity. Böhme, B., VandenBos, T., Cerretti, D.P., Park, L.S., Holtrich, U., Rübsamen-Waigmann, H., Strebhardt, K. J. Biol. Chem. (1996) [Pubmed]
  23. Reverse endocytosis of transmembrane ephrin-B ligands via a clathrin-mediated pathway. Parker, M., Roberts, R., Enriquez, M., Zhao, X., Takahashi, T., Pat Cerretti, D., Daniel, T., Chen, J. Biochem. Biophys. Res. Commun. (2004) [Pubmed]
  24. Role of numb in dendritic spine development with a Cdc42 GEF intersectin and EphB2. Nishimura, T., Yamaguchi, T., Tokunaga, A., Hara, A., Hamaguchi, T., Kato, K., Iwamatsu, A., Okano, H., Kaibuchi, K. Mol. Biol. Cell (2006) [Pubmed]
  25. The C-terminus of ephrin-B1 regulates metalloproteinase secretion and invasion of cancer cells. Tanaka, M., Sasaki, K., Kamata, R., Sakai, R. J. Cell. Sci. (2007) [Pubmed]
  26. 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]
  27. Coexpression of transcripts encoding EPHB receptor protein tyrosine kinases and their ephrin-B ligands in human small cell lung carcinoma. Tang, X.X., Brodeur, G.M., Campling, B.G., Ikegaki, N. Clin. Cancer Res. (1999) [Pubmed]
  28. 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]
  29. 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]
  30. In vivo tyrosine phosphorylation sites of activated ephrin-B1 and ephB2 from neural tissue. Kalo, M.S., Yu, H.H., Pasquale, E.B. J. Biol. Chem. (2001) [Pubmed]
 
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