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Gene Review

EPHB4  -  EPH receptor B4

Homo sapiens

Synonyms: Ephrin type-B receptor 4, HTK, Hepatoma transmembrane kinase, MYK1, TYRO11, ...
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Disease relevance of EPHB4


High impact information on EPHB4

  • Receptor tyrosine kinase, EphB4 (HTK), accelerates differentiation of select human hematopoietic cells [7].
  • Immunohistochemical analysis of one of the newly identified correlated L-R pairs (i.e., EFNB3-EPHB4) revealed the correlated expression of ephrin-B3 and EphB4 proteins in 45 of 55 epithelial ovarian tumor samples (P < 0.0001) [8].
  • In vitro cytotrophoblasts avoided EPHB4-coated substrates; upon co-culture with 3T3 cells expressing this molecule, their migration was significantly inhibited [9].
  • When cytotrophoblasts encounter EPHB4 expressed by venous endothelium, ephrin B-generated repulsive signals and a reduction in chemokine-mediated responses limit their interaction with veins [9].
  • Additionally, cytotrophoblast commitment to uterine invasion was accompanied by rapid downregulation of EPHB4, a transmembrane receptor associated with venous identity, and upregulation of ephrin B1 [9].

Chemical compound and disease context of EPHB4


Biological context of EPHB4


Anatomical context of EPHB4

  • We propose that EPHB4/ephrin B1 interactions generate repulsive signals that direct cytotrophoblast invasion toward the uterus, where chemokines stimulate cytotrophoblast migration through the decidua [9].
  • METHODS: Ten and 11 liver grafts were perfused via the portal vein with University of Wisconsin solutions (UW group) and Bretschneider's Histidine-Tryptophan-Ketoglutarate solutions (HTK group), respectively [14].
  • When cultured hepatocytes were incubated in HTK solution or in modified Krebs-Henseleit buffer containing 198 mM L-histidine at 37 degrees C, most cells lost viability within 3 h (LDH release 86 +/- 7% and 89 +/- 5%, respectively) [15].
  • METHODS: A telomerase-infected, extended-lifespan human corneal fibroblast cell line (HTK) was transfected by using a vector for enhanced green fluorescent protein (GFP)-alpha-actinin [16].
  • UW is superior to Celsior and HTK in the protection of human liver endothelial cells against preservation injury [17].

Associations of EPHB4 with chemical compounds

  • Chemical modification experiments of cysteine residues have shown that the cysteine residues of HTK are less accessible to an SH reagent than those of the preevolved KNT [18].
  • The superior protection provided by Bretschneider HTK was due to its additives histidine, tryptophan, and KH-2-oxygluterate (p less than 0.005), and to its low chloride content (p less than 0.005) [4].
  • In Group A, in which ketoglutarate was excluded from the HTK solution, percent developed pressure was significantly decreased (p<0.01) and the released enzyme (CK-MB) was significantly increased, but coronary flow was not significantly changed [19].
  • The aim of our study was to compare the protective effect of UW and HTK solutions on preservation-induced injury of jejunal grafts, as evaluated by the histological changes (semiquantitative method) and small bowel mucosal serotonin levels (as a possible new quantitative method) [20].
  • Therefore, histidine-tryptophan-ketoglutarate solution (HTK; alpha-ketoglutarate) and University of Wisconsin solution (UW; adenosine) were supplied with energy substrates to achieve graft viability [21].

Other interactions of EPHB4


Analytical, diagnostic and therapeutic context of EPHB4


  1. 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]
  2. Significance and molecular targets of protein kinase A during cAMP-mediated protection of cold stored liver grafts. Akbar, S., Minor, T. Cell. Mol. Life Sci. (2001) [Pubmed]
  3. Impact of polysol, a newly developed preservation solution, on cold storage of steatotic rat livers. Hata, K., Tolba, R.H., Wei, L., Doorschodt, B.M., B??ttner, R., Yamamoto, Y., Minor, T. Liver Transpl. (2007) [Pubmed]
  4. Endothelial cell toxicity of solid-organ preservation solutions. von Oppell, U.O., Pfeiffer, S., Preiss, P., Dunne, T., Zilla, P., Reichart, B. Ann. Thorac. Surg. (1990) [Pubmed]
  5. Selective killing of cancer cells based on translational control of a suicide gene. DeFatta, R.J., Li, Y., De Benedetti, A. Cancer Gene Ther. (2002) [Pubmed]
  6. EPHB4 and survival of colorectal cancer patients. Davalos, V., Dopeso, H., Castaño, J., Wilson, A.J., Vilardell, F., Romero-Gimenez, J., Espín, E., Armengol, M., Capella, G., Mariadason, J.M., Aaltonen, L.A., Schwartz, S., Arango, D. Cancer Res. (2006) [Pubmed]
  7. Receptor tyrosine kinase, EphB4 (HTK), accelerates differentiation of select human hematopoietic cells. Wang, Z., Miura, N., Bonelli, A., Mole, P., Carlesso, N., Olson, D.P., Scadden, D.T. Blood (2002) [Pubmed]
  8. New potential ligand-receptor signaling loops in ovarian cancer identified in multiple gene expression studies. Castellano, G., Reid, J.F., Alberti, P., Carcangiu, M.L., Tomassetti, A., Canevari, S. Cancer Res. (2006) [Pubmed]
  9. 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]
  10. A simplified general method for determination of recombinant retrovirus titers. Miyao, Y., Shimizu, K., Tamura, M., Yamada, M., Tamura, K., Nakahira, K., Kuriyama, S., Hayakawa, T., Ikenaka, K. Cell Struct. Funct. (1995) [Pubmed]
  11. Treatment of glioblastoma by direct inoculation of concentrated high titer-recombinant retrovirus carrying the herpes simplex virus thymidine kinase gene. Ikenaka, K., Sasaki, M., Tamura, K., Tamura, M., Miyao, Y., Nanmoku, K., Kawano, Y., Nakahira, K., Yoshimine, T., Shimizu, K. Hum. Cell (2001) [Pubmed]
  12. EphB4 provides survival advantage to squamous cell carcinoma of the head and neck. Masood, R., Kumar, S.R., Sinha, U.K., Crowe, D.L., Krasnoperov, V., Reddy, R.K., Zozulya, S., Singh, J., Xia, G., Broek, D., Schönthal, A.H., Gill, P.S. Int. J. Cancer (2006) [Pubmed]
  13. Cloning and characterization of HTK, a novel transmembrane tyrosine kinase of the EPH subfamily. Bennett, B.D., Wang, Z., Kuang, W.J., Wang, A., Groopman, J.E., Goeddel, D.V., Scadden, D.T. J. Biol. Chem. (1994) [Pubmed]
  14. Exposure of hepatic sinusoidal mononuclear cells to UW solution in situ but not ex vivo induces apoptosis. Kinoshita, K., Ikai, I., Gomi, T., Kanai, M., Tsuyuki, S., Hirose, T., Kawai, Y., Yamauchi, A., Inamoto, T., Inomata, Y., Tanaka, K., Yamaoka, Y. J. Hepatol. (1998) [Pubmed]
  15. Histidine-induced injury to cultured liver cells, effects of histidine derivatives and of iron chelators. Rauen, U., Klempt, S., de Groot, H. Cell. Mol. Life Sci. (2007) [Pubmed]
  16. Modulation of corneal fibroblast contractility within fibrillar collagen matrices. Vishwanath, M., Ma, L., Otey, C.A., Jester, J.V., Petroll, W.M. Invest. Ophthalmol. Vis. Sci. (2003) [Pubmed]
  17. UW is superior to Celsior and HTK in the protection of human liver endothelial cells against preservation injury. Janssen, H., Janssen, P.H., Broelsch, C.E. Liver Transpl. (2004) [Pubmed]
  18. Increased rigidity of domain structures enhances the stability of a mutant enzyme created by directed evolution. Hoseki, J., Okamoto, A., Takada, N., Suenaga, A., Futatsugi, N., Konagaya, A., Taiji, M., Yano, T., Kuramitsu, S., Kagamiyama, H. Biochemistry (2003) [Pubmed]
  19. Effect of HTK solution for myocardial preservation. Hachida, M., Ookado, A., Nonoyama, M., Koyanagi, H. The Journal of cardiovascular surgery. (1996) [Pubmed]
  20. Preservation injury of jejunal grafts and its modulation by custodiol and university of wisconsin perfusion solutions in wistar rats. Baláz, P., Matia, I., Jackanin, S., Rybárová, E., Kron, I., Pomfy, M., Fronek, J., Ryska, M. European surgical research. Europäische chirurgische Forschung. Recherches chirurgicales européennes. (2004) [Pubmed]
  21. Value of energy substrates in HTK and UW to protect human liver endothelial cells against ischemia and reperfusion injury. Janssen, H., Janssen, P.H., Broelsch, C.E. European surgical research. Europäische chirurgische Forschung. Recherches chirurgicales européennes. (2004) [Pubmed]
  22. Expression of Ephb2 and Ephb4 in breast carcinoma. Wu, Q., Suo, Z., Risberg, B., Karlsson, M.G., Villman, K., Nesland, J.M. Pathol. Oncol. Res. (2004) [Pubmed]
  23. Does using HTK solution for cold perfusion of cadaveric kidneys save money? Englesbe, M.J., Heidt, D., Sung, R., Pietroski, R. Transplantation (2006) [Pubmed]
  24. Preservation of canine liver grafts using HTK solution. van Gulik, T.M., Reinders, M.E., Nio, R., Frederiks, W.M., Bosma, A., Klopper, P.J. Transplantation (1994) [Pubmed]
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