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Gene Review

EPHB2  -  EPH receptor B2

Homo sapiens

Synonyms: CAPB, DRT, Developmentally-regulated Eph-related tyrosine kinase, EK5, ELK-related tyrosine kinase, ...
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Disease relevance of EPHB2


Psychiatry related information on EPHB2

  • While we previously demonstrated that ERK is activated in Alzheimer's disease, the upstream cascade leading to its activation had not been fully examined [4].
  • Drug addiction results in part from the distortion of dopamine-controlled plasticity, and extracellular signal-regulated kinase (ERK) plays an important role in the underlying molecular mechanisms of this process [5].
  • At least in this study, a life style of physical activity appeared to play a more dominant role in determining SRT, DRT, and MT than age [6].
  • The SRT, DRT, and MT of older men (OA) who have experienced a life style of chronic physical activity were compared to those of nonactive men of similar age (ONA), and also to active (YA) and nonactive young men (YNA) [6].
  • Cross-sectional analyses revealed slowing of simple (SRT) and relatively greater slowing of disjunctive (DRT; aka "go-no-go") reaction time across decades for both males and females [7].

High impact information on EPHB2

  • Inhibition of ERK activation partially inhibits T48 phosphorylation, Cdc25C activation, and mitotic induction [8].
  • This approach enabled us to identify previously unknown mutations in the receptor tyrosine kinase gene EPHB2 [1].
  • Transfection of DU 145 cells, which lack functional EphB2, with wild-type EPHB2 suppresses clonogenic growth [1].
  • Transactivation joins multiple tracks to the ERK/MAPK cascade [9].
  • This pathway is responsible for several of the effects of SDF-1alpha on T cells, including prolonged ERK MAP kinase activity, increased intracellular calcium ion concentrations, robust AP-1 transcriptional activity, and SDF-1alpha costimulation of cytokine secretion [10].

Chemical compound and disease context of EPHB2


Biological context of EPHB2


Anatomical context of EPHB2


Associations of EPHB2 with chemical compounds

  • The EPHB2v protein lacks one arginine residue that resides immediately following the EPHB2 transmembrane domain [2].
  • Certain studies report sequential activation of cGMP-dependent protein kinase (PKG) and p38/ERK pathways by platelet agonists, leading to integrin activation and secretion, whereas others establish an essential role of Src/ERK-mediated TxA(2) generation for fibrinogen receptor activation in human platelets [17].
  • A reduction in the downstream signalling effector phosphorylated ERK was seen in both resistant cell lines when GW282974A was used in combination with either cisplatin or paclitaxel [18].
  • Enamel Matrix Derivative Stimulates Human Gingival Fibroblast Proliferation via ERK [15].
  • The increased expression of Egr-1 and Bcl-2 by isoflurane was inhibited by ERK inhibition [12].

Regulatory relationships of EPHB2

  • Cotreatment with the Rho kinase inhibitors Y-27632 and H1152 attenuated the CaR-induced morphological change but not intracellular Ca2+ (Ca2+(i)) mobilization or ERK activation, although transfection with a dominant-negative RhoA-binding protein also inhibited calcimimetic-induced actin stress fiber assembly [19].
  • Neuroprotection was due to the inhibition of NMDA-induced apoptosis through ERK activation [20].

Other interactions of EPHB2

  • 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 [3].
  • Expression profile of EFNB1, EFNB2, two ligands of EPHB2 in human gastric cancer [3].
  • This effect was partially reduced by PKG inhibition and completely abolished by PKA inhibition.We conclude that sildenafil exerts an antiproliferative effect on human PASMC that is mediated by an interaction between the cGMP-PKG and the cAMP-PKA activated pathways, leading to inhibition of PDGF-mediated activation of the ERK [21].
  • Association among EPHB2, TrkA, and MYCN expression in low-stage neuroblastomas [22].
  • OBJECTIVE: The RYK, EPHB2, and EPHB3 genes are attractive candidates for cleft lip and/or palate and cleft palate only pathogenesis [23].

Analytical, diagnostic and therapeutic context of EPHB2


  1. Nonsense-mediated decay microarray analysis identifies mutations of EPHB2 in human prostate cancer. Huusko, P., Ponciano-Jackson, D., Wolf, M., Kiefer, J.A., Azorsa, D.O., Tuzmen, S., Weaver, D., Robbins, C., Moses, T., Allinen, M., Hautaniemi, S., Chen, Y., Elkahloun, A., Basik, M., Bova, G.S., Bubendorf, L., Lugli, A., Sauter, G., Schleutker, J., Ozcelik, H., Elowe, S., Pawson, T., Trent, J.M., Carpten, J.D., Kallioniemi, O.P., Mousses, S. Nat. Genet. (2004) [Pubmed]
  2. A variant transcript encoding an isoform of the human protein tyrosine kinase EPHB2 is generated by alternative splicing and alternative use of polyadenylation signals. Tang, X.X., Pleasure, D.E., Brodeur, G.M., Ikegaki, N. Oncogene (1998) [Pubmed]
  3. 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]
  4. Distribution, levels and phosphorylation of Raf-1 in Alzheimer's disease. Mei, M., Su, B., Harrison, K., Chao, M., Siedlak, S.L., Previll, L.A., Jackson, L., Cai, D.X., Zhu, X. J. Neurochem. (2006) [Pubmed]
  5. ERK2: a logical AND gate critical for drug-induced plasticity? Girault, J.A., Valjent, E., Caboche, J., Hervé, D. Current opinion in pharmacology (2007) [Pubmed]
  6. Reaction and movement time as a function of age and physical activity level. Spirduso, W.W. Journal of gerontology. (1975) [Pubmed]
  7. Age differences and changes in reaction time: the Baltimore Longitudinal Study of Aging. Fozard, J.L., Vercryssen, M., Reynolds, S.L., Hancock, P.A., Quilter, R.E. Journal of gerontology. (1994) [Pubmed]
  8. Regulation of Cdc25C by ERK-MAP Kinases during the G(2)/M Transition. Wang, R., He, G., Nelman-Gonzalez, M., Ashorn, C.L., Gallick, G.E., Stukenberg, P.T., Kirschner, M.W., Kuang, J. Cell (2007) [Pubmed]
  9. Transactivation joins multiple tracks to the ERK/MAPK cascade. Wetzker, R., Böhmer, F.D. Nat. Rev. Mol. Cell Biol. (2003) [Pubmed]
  10. CXCR4 physically associates with the T cell receptor to signal in T cells. Kumar, A., Humphreys, T.D., Kremer, K.N., Bramati, P.S., Bradfield, L., Edgar, C.E., Hedin, K.E. Immunity (2006) [Pubmed]
  11. Molecular characterization and chromosomal localization of DRT (EPHT3): a developmentally regulated human protein-tyrosine kinase gene of the EPH family. Ikegaki, N., Tang, X.X., Liu, X.G., Biegel, J.A., Allen, C., Yoshioka, A., Sulman, E.P., Brodeur, G.M., Pleasure, D.E. Hum. Mol. Genet. (1995) [Pubmed]
  12. Isoflurane preconditioning protects human neuroblastoma SH-SY5Y cells against in vitro simulated ischemia-reperfusion through the activation of extracellular signal-regulated kinases pathway. Zuo, Z., Wang, Y., Huang, Y. Eur. J. Pharmacol. (2006) [Pubmed]
  13. The adhesion molecule L1 (CD171) promotes melanoma progression. Meier, F., Busch, S., Gast, D., Göppert, A., Altevogt, P., Maczey, E., Riedle, S., Garbe, C., Schittek, B. Int. J. Cancer (2006) [Pubmed]
  14. Mechanisms of inactivation of the receptor tyrosine kinase EPHB2 in colorectal tumors. Alazzouzi, H., Davalos, V., Kokko, A., Domingo, E., Woerner, S.M., Wilson, A.J., Konrad, L., Laiho, P., Espín, E., Armengol, M., Imai, K., Yamamoto, H., Mariadason, J.M., Gebert, J.F., Aaltonen, L.A., Schwartz, S., Arango, D. Cancer Res. (2005) [Pubmed]
  15. Enamel Matrix Derivative Stimulates Human Gingival Fibroblast Proliferation via ERK. Zeldich, E., Koren, R., Nemcovsky, C., Weinreb, M. J. Dent. Res. (2007) [Pubmed]
  16. Chloramphenicol induces in vitro growth arrest and apoptosis of human keratinocytes. Popadic, S., Popadic, D., Ramic, Z., Stojkovic, M.M., Trajkovic, V., Milinkovic, M., Medenica, L. Cell Biol. Toxicol. (2006) [Pubmed]
  17. Thrombin stimulation of p38 MAP kinase in human platelets is mediated by ADP and thromboxane A2 and inhibited by cGMP/cGMP-dependent protein kinase. Begonja, A.J., Geiger, J., Rukoyatkina, N., Rauchfuss, S., Gambaryan, S., Walter, U. Blood (2007) [Pubmed]
  18. Receptor tyrosine kinase (RTK) inhibition is effective in chemosensitising EGFR-expressing drug resistant human ovarian cancer cell lines when used in combination with cytotoxic agents. Coley, H.M., Shotton, C.F., Ajose-Adeogun, A., Modjtahedi, H., Thomas, H. Biochem. Pharmacol. (2006) [Pubmed]
  19. Ca2+-sensing receptor induces Rho kinase-mediated actin stress fiber assembly and altered cell morphology, but not in response to aromatic amino acids. Davies, S.L., Gibbons, C.E., Vizard, T., Ward, D.T. Am. J. Physiol., Cell Physiol. (2006) [Pubmed]
  20. The HSV-2 protein ICP10PK prevents neuronal apoptosis and loss of function in an in vivo model of neurodegeneration associated with glutamate excitotoxicity. Golembewski, E.K., Wales, S.Q., Aurelian, L., Yarowsky, P.J. Exp. Neurol. (2007) [Pubmed]
  21. Antiproliferative effect of sildenafil on human pulmonary artery smooth muscle cells. Tantini, B., Manes, A., Fiumana, E., Pignatti, C., Guarnieri, C., Zannoli, R., Md, A.B., Galiè, N. Basic Res. Cardiol. (2005) [Pubmed]
  22. 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]
  23. A mutation in RYK is a genetic factor for nonsyndromic cleft lip and palate. Watanabe, A., Akita, S., Tin, N.T., Natsume, N., Nakano, Y., Niikawa, N., Uchiyama, T., Yoshiura, K. Cleft Palate Craniofac. J. (2006) [Pubmed]
  24. Overexpression of ERK, an EPH family receptor protein tyrosine kinase, in various human tumors. Kiyokawa, E., Takai, S., Tanaka, M., Iwase, T., Suzuki, M., Xiang, Y.Y., Naito, Y., Yamada, K., Sugimura, H., Kino, I. Cancer Res. (1994) [Pubmed]
  25. (+/-)-2-Chloropropionic acid elevates reactive oxygen species formation in human neutrophil granulocytes. Aam, B.B., Fonnum, F. Toxicology (2006) [Pubmed]
  26. Inhibition of Tumor Endothelial ERK Activation, Angiogenesis, and Tumor Growth by Sorafenib (BAY43-9006). Murphy, D.A., Makonnen, S., Lassoued, W., Feldman, M.D., Carter, C., Lee, W.M. Am. J. Pathol. (2006) [Pubmed]
  27. ERK binds, phosphorylates InsP3 type 1 receptor and regulates intracellular calcium dynamics in DT40 cells. Yang, L.H., Bai, G.R., Huang, X.Y., Sun, F.Z. Biochem. Biophys. Res. Commun. (2006) [Pubmed]
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