ephb4 receptor


Summary: An eph family receptor found in a variety of adult and embryonic tissues. Unlike the majority of proteins in this class there is little or no expression of EphB4 receptor in the BRAIN. It has been found at high levels in developing mammary glands and in invasive mammary tumors.

Top Publications

  1. Noren N, Lu M, Freeman A, Koolpe M, Pasquale E. Interplay between EphB4 on tumor cells and vascular ephrin-B2 regulates tumor growth. Proc Natl Acad Sci U S A. 2004;101:5583-8 pubmed
    ..These results support a model in which EphB4 promotes tumor growth by stimulating angiogenesis through ephrin-B2. ..
  2. Alam S, Fujimoto J, Jahan I, Sato E, Tamaya T. Overexpression of ephrinB2 and EphB4 in tumor advancement of uterine endometrial cancers. Ann Oncol. 2007;18:485-90 pubmed
    ..Therefore, ephrinB2/EphB4 might work on tumor advancement and may be recognized as a novel prognostic indicator for uterine endometrial cancers. ..
  3. Wu Q, Suo Z, Risberg B, Karlsson M, Villman K, Nesland J. Expression of Ephb2 and Ephb4 in breast carcinoma. Pathol Oncol Res. 2004;10:26-33 pubmed
    ..These findings indicate that both EphB2 and EphB4 are involved in the development of breast cancer and that both molecules could be potential predictive markers. ..
  4. Füller T, Korff T, Kilian A, Dandekar G, Augustin H. Forward EphB4 signaling in endothelial cells controls cellular repulsion and segregation from ephrinB2 positive cells. J Cell Sci. 2003;116:2461-70 pubmed
    ..Taken together, these data identify distinct propulsive and repulsive effector functions of endothelial ephrinB2 and EphB4 that mediate spatial positional signals during angiogenesis and vessel assembly. ..
  5. Yang N, Pasquale E, Owen L, Ethell I. The EphB4 receptor-tyrosine kinase promotes the migration of melanoma cells through Rho-mediated actin cytoskeleton reorganization. J Biol Chem. 2006;281:32574-86 pubmed
    ..Highly malignant melanoma cells express the highest levels of EphB4 receptor and migrate faster than less malignant melanoma cells...
  6. Castellano G, Reid J, Alberti P, Carcangiu M, Tomassetti A, Canevari S. New potential ligand-receptor signaling loops in ovarian cancer identified in multiple gene expression studies. Cancer Res. 2006;66:10709-19 pubmed
  7. Munarini N, Jäger R, Abderhalden S, Zuercher G, Rohrbach V, Loercher S, et al. Altered mammary epithelial development, pattern formation and involution in transgenic mice expressing the EphB4 receptor tyrosine kinase. J Cell Sci. 2002;115:25-37 pubmed
    We have previously documented the cell-type-specific and hormone-dependent expression of the EphB4 receptor in the mouse mammary gland...
  8. Kwan Tat S, Pelletier J, Amiable N, Boileau C, Lajeunesse D, Duval N, et al. Activation of the receptor EphB4 by its specific ligand ephrin B2 in human osteoarthritic subchondral bone osteoblasts. Arthritis Rheum. 2008;58:3820-30 pubmed publisher
    ..The presence of the EphB4 receptor was determined by immunohistochemistry, and its expression level, modulation upon treatment, and consequences ..
  9. Lee Y, Perren J, Douglas E, Raynor M, Bartley M, Bardy P, et al. Investigation of the expression of the EphB4 receptor tyrosine kinase in prostate carcinoma. BMC Cancer. 2005;5:119 pubmed
    The EphB4 receptor tyrosine kinase has been reported as increased in tumours originating from several different tissues and its expression in a prostate cancer xenograft model has been reported...

More Information


  1. Xia G, Kumar S, Stein J, Singh J, Krasnoperov V, Zhu S, et al. EphB4 receptor tyrosine kinase is expressed in bladder cancer and provides signals for cell survival. Oncogene. 2006;25:769-80 pubmed
    ..EphB4 is thus a potential candidate as a predictor of disease outcome in bladder cancer and as target for novel therapy. ..
  2. Kumar S, Singh J, Xia G, Krasnoperov V, Hassanieh L, Ley E, et al. Receptor tyrosine kinase EphB4 is a survival factor in breast cancer. Am J Pathol. 2006;169:279-93 pubmed
    ..Our data indicate that biologically active EphB4 functions as a survival factor in breast cancer and is a novel target for therapy. ..
  3. Sinha U, Kundra A, Scalia P, Smith D, Parsa B, Masood R, et al. Expression of EphB4 in head and neck squamous cell carcinoma. Ear Nose Throat J. 2003;82:866, 869-70, 887 pubmed
    ..In each of the six patients, expression was greater in the metastatic tumor than in the primary tumor. We conclude that EphB4 is a novel target in the treatment of HNSCC. ..
  4. Zhao C, Irie N, Takada Y, Shimoda K, Miyamoto T, Nishiwaki T, et al. Bidirectional ephrinB2-EphB4 signaling controls bone homeostasis. Cell Metab. 2006;4:111-21 pubmed
    ..These data demonstrate that ephrin-Eph bidirectional signaling links two major molecular mechanisms for cell differentiation--one in osteoclasts and the other in osteoblasts--thereby maintaining bone homeostasis. ..
  5. Takai N, Miyazaki T, Fujisawa K, Nasu K, Miyakawa I. Expression of receptor tyrosine kinase EphB4 and its ligand ephrin-B2 is associated with malignant potential in endometrial cancer. Oncol Rep. 2001;8:567-73 pubmed
    ..Furthermore, these results suggest that EphB4 receptor kinase may modulate the biological behavior of endometrial carcinomas through autocrine and/or paracrine ..
  6. Masood R, Kumar S, Sinha U, Crowe D, Krasnoperov V, Reddy R, et al. EphB4 provides survival advantage to squamous cell carcinoma of the head and neck. Int J Cancer. 2006;119:1236-48 pubmed
    ..Expression of EphB4 in HNSCC tumor cells confers survival and invasive properties, and thereby provides a strong rationale for targeting EphB4 as novel therapy for HNSCC. ..
  7. Wu Q, Suo Z, Kristensen G, Baekelandt M, Nesland J. The prognostic impact of EphB2/B4 expression on patients with advanced ovarian carcinoma. Gynecol Oncol. 2006;102:15-21 pubmed
    ..03) or EphB4 (P = 0.003) receptors had poorer survival, and patients with strong immunostaining for EphB4 receptor showed poorer response to chemotherapy (P = 0.036)...
  8. Noren N, Pasquale E. Paradoxes of the EphB4 receptor in cancer. Cancer Res. 2007;67:3994-7 pubmed
    ..Understanding the multifaceted role of EphB4 in tumorigenesis may allow the development of new anticancer therapies. ..
  9. Liu W, Ahmad S, Jung Y, Reinmuth N, Fan F, Bucana C, et al. Coexpression of ephrin-Bs and their receptors in colon carcinoma. Cancer. 2002;94:934-9 pubmed
    ..Further studies are necessary to determine the functional role of ephrin-Bs in colon carcinoma angiogenesis and growth. ..
  10. Berclaz G, Karamitopoulou E, Mazzucchelli L, Rohrbach V, Dreher E, Ziemiecki A, et al. Activation of the receptor protein tyrosine kinase EphB4 in endometrial hyperplasia and endometrial carcinoma. Ann Oncol. 2003;14:220-6 pubmed
    ..007). These findings indicate that in the endometrium, EphB4 is an early indicator of malignant development and, thus, EphB4 may represent a potent tool for diagnosis and therapeutic intervention. ..
  11. Andres A, Munarini N, Djonov V, Bruneau S, Zuercher G, Loercher S, et al. EphB4 receptor tyrosine kinase transgenic mice develop glomerulopathies reminiscent of aglomerular vascular shunts. Mech Dev. 2003;120:511-6 pubmed
    We have established transgenic mice over-expressing the EphB4 receptor tyrosine kinase in the kidney. The EphB4 protein was localised to the developing tubular system of both control and transgenic newborn mice...
  12. Xia G, Kumar S, Masood R, Zhu S, Reddy R, Krasnoperov V, et al. EphB4 expression and biological significance in prostate cancer. Cancer Res. 2005;65:4623-32 pubmed
    ..These data show a role for EphB4 in prostate cancer and provide a rationale to study EphB4 for diagnostic, prognostic, and therapeutic applications. ..
  13. Berclaz G, Andres A, Albrecht D, Dreher E, Ziemiecki A, Gusterson B, et al. Expression of the receptor protein tyrosine kinase myk-1/htk in normal and malignant mammary epithelium. Biochem Biophys Res Commun. 1996;226:869-75 pubmed
    ..The specific epithelial expression of the myk-1/htk receptor PTK suggest a specialised role of this eph-related PTK in the differentiation and/or maintenance of secretory epithelium in the adult. ..
  14. Noren N, Yang N, Silldorff M, Mutyala R, Pasquale E. Ephrin-independent regulation of cell substrate adhesion by the EphB4 receptor. Biochem J. 2009;422:433-42 pubmed publisher
    ..These findings demonstrate that EphB4 can affect cancer cell behaviour in an ephrin-independent manner. ..
  15. Berclaz G, Flütsch B, Altermatt H, Rohrbach V, Djonov V, Ziemiecki A, et al. Loss of EphB4 receptor tyrosine kinase protein expression during carcinogenesis of the human breast. Oncol Rep. 2002;9:985-9 pubmed
    ..002) suggesting that in breast cancer, EphB4 expression is not compatible with tumor progression. This raises the possibility that EphB4 could represent a potent tool for therapeutic intervention. ..
  16. Bennett B, Wang Z, Kuang W, Wang A, Groopman J, Goeddel D, et al. Cloning and characterization of HTK, a novel transmembrane tyrosine kinase of the EPH subfamily. J Biol Chem. 1994;269:14211-8 pubmed
    ..The novel transmembrane protein, Htk, may function as a receptor with an expression pattern suggesting a role in events mediating differentiation and development. ..
  17. Bruhl T, Urbich C, Aicher D, Acker Palmer A, Zeiher A, Dimmeler S. Homeobox A9 transcriptionally regulates the EphB4 receptor to modulate endothelial cell migration and tube formation. Circ Res. 2004;94:743-51 pubmed
    ..role of HoxA9 for endothelial cell migration and angiogenesis in vitro and identified a novel target gene, the EphB4 receptor. Inhibition of HoxA9 expression decreased endothelial cell tube formation and inhibited endothelial cell ..
  18. Martiny Baron G, Korff T, Schaffner F, Esser N, Eggstein S, Marme D, et al. Inhibition of tumor growth and angiogenesis by soluble EphB4. Neoplasia. 2004;6:248-57 pubmed
    ..Taken together, the data identify dual effects of sEphB4 on the tumor and the vascular compartment that collectively inhibit tumor growth. ..
  19. Noren N, Foos G, Hauser C, Pasquale E. The EphB4 receptor suppresses breast cancer cell tumorigenicity through an Abl-Crk pathway. Nat Cell Biol. 2006;8:815-25 pubmed
    ..Here, we report that the EphB4 receptor can behave as a tumour suppressor in a mouse xenograft model of breast cancer when stimulated by its ligand, ..
  20. Mundy G, Elefteriou F. Boning up on ephrin signaling. Cell. 2006;126:441-3 pubmed
    ..Such bidirectional signaling limits osteoclast activity while stimulating osteoblast differentiation. ..
  21. Zamora D, Babra B, Pan Y, Planck S, Rosenbaum J. Human leukocytes express ephrinB2 which activates microvascular endothelial cells. Cell Immunol. 2006;242:99-109 pubmed
    ..This suggests a novel mechanism by which EC and lymphocytes communicate to regulate cell activation/migration during inflammation. ..
  22. Yuan K, Hong T, Chen J, Tsai W, Lin M. Syndecan-1 up-regulated by ephrinB2/EphB4 plays dual roles in inflammatory angiogenesis. Blood. 2004;104:1025-33 pubmed
    ..Depending on the presence of heparanases, the roles of syndecan-1 may be opposite in different physiological settings. ..
  23. Asundi V, Carey D. Phosphorylation of recombinant N-syndecan (syndecan 3) core protein. Biochem Biophys Res Commun. 1997;240:502-6 pubmed
    ..Our results clearly demonstrate that the tyrosine residues in the cytoplasmic domain of N-syndecan can be phosphorylated by a tyrosine-specific kinase, and that all four tyrosine residues are capable of being phosphorylated. ..
  24. Luiz de Freitas P, Li M, Ninomiya T, Nakamura M, Ubaidus S, Oda K, et al. Intermittent PTH administration stimulates pre-osteoblastic proliferation without leading to enhanced bone formation in osteoclast-less c-fos(-/-) mice. J Bone Miner Res. 2009;24:1586-97 pubmed publisher
  25. Umeda N, Ozaki H, Hayashi H, Oshima K. Expression of ephrinB2 and its receptors on fibroproliferative membranes in ocular angiogenic diseases. Am J Ophthalmol. 2004;138:270-9 pubmed
    ..These data suggest that the ephrinB2-EphB2/B3 system may play an important role in ocular angiogenesis. ..
  26. Ganetzky B, Robertson G, Wilson G, Trudeau M, Titus S. The eag family of K+ channels in Drosophila and mammals. Ann N Y Acad Sci. 1999;868:356-69 pubmed
    ..Biochemical evidence indicates a direct physical interaction between EAG and HK proteins. Overall, these studies highlight the diverse properties of the eag family of K+ channels, which are likely to subserve diverse functions in vivo. ..
  27. Krasnoperov V, Kumar S, Ley E, Li X, Scehnet J, Liu R, et al. Novel EphB4 monoclonal antibodies modulate angiogenesis and inhibit tumor growth. Am J Pathol. 2010;176:2029-38 pubmed publisher
    b>EphB4 receptor tyrosine kinase and its cognate ligand EphrinB2 regulate induction and maturation of newly forming vessels. Inhibition of their interaction arrests angiogenesis, vessel maturation, and pericyte recruitment...
  28. Warren N, Voloudakis G, Yoon Y, Robakis N, Georgakopoulos A. The product of the γ-secretase processing of ephrinB2 regulates VE-cadherin complexes and angiogenesis. Cell Mol Life Sci. 2018;75:2813-2826 pubmed publisher
    ..that the cytosolic peptide efnB2/CTF2 produced by the PS1/γ-secretase cleavage of efnB2 ligand promotes EphB4 receptor-dependent angiogenesis in vitro...
  29. Birgbauer E, Oster S, Severin C, Sretavan D. Retinal axon growth cones respond to EphB extracellular domains as inhibitory axon guidance cues. Development. 2001;128:3041-8 pubmed
    ..In conclusion, development of neuronal connectivity may involve the combined activity of Eph proteins serving as guidance receptors and as axon guidance cues. ..
  30. Knaust R, Nordlund P. Screening for soluble expression of recombinant proteins in a 96-well format. Anal Biochem. 2001;297:79-85 pubmed
    ..The method is well suited for automation and should be applicable to expression screening of most proteins and fusion domains to which specific antibodies are available. ..
  31. Kumar S, Masood R, Spannuth W, Singh J, Scehnet J, Kleiber G, et al. The receptor tyrosine kinase EphB4 is overexpressed in ovarian cancer, provides survival signals and predicts poor outcome. Br J Cancer. 2007;96:1083-91 pubmed
    ..Furthermore, EphB4 antisense significantly inhibited growth of ovarian tumour xenografts and tumour microvasculature in vivo. Inhibition of EphB4 may hence have prognostic and therapeutic utility in ovarian carcinoma. ..
  32. Red Horse K, Kapidzic M, Zhou Y, Feng K, Singh H, Fisher S. EPHB4 regulates chemokine-evoked trophoblast responses: a mechanism for incorporating the human placenta into the maternal circulation. Development. 2005;132:4097-106 pubmed
    ..When they encounter ephrin B2 ligands expressed in uterine arterioles, migration is permitted. The net effect is preferential cytotrophoblast remodeling of arterioles, a hallmark of human placentation. ..
  33. Ferguson B, Tan Y, Kanteti R, Liu R, Gayed M, Vokes E, et al. Novel EPHB4 Receptor Tyrosine Kinase Mutations and Kinomic Pathway Analysis in Lung Cancer. Sci Rep. 2015;5:10641 pubmed publisher
    Lung cancer outcomes remain poor despite the identification of several potential therapeutic targets. The EPHB4 receptor tyrosine kinase (RTK) has recently emerged as an oncogenic factor in many cancers, including lung cancer...
  34. Dalva M, Takasu M, Lin M, Shamah S, Hu L, Gale N, et al. EphB receptors interact with NMDA receptors and regulate excitatory synapse formation. Cell. 2000;103:945-56 pubmed
    ..These findings indicate that EphrinB activation of EphB promotes an association of EphB with NMDA receptors that may be critical for synapse development or function. ..
  35. Wang Z, Xuan S, Qiu W, Zhu J, Guo X, Li W, et al. Near infrared light mediated photochemotherapy for efficiently treating deep orthotopic tumors guided by ultrasound imaging. Drug Deliv. 2017;24:1441-1452 pubmed publisher
    ..Here, we reported an EphB4 receptor-targeting polymeric nanoplatform containing hollow gold nanospheres (HAuNS) and the anticancer drug paclitaxel ..
  36. Hubbard S. Theme and variations: juxtamembrane regulation of receptor protein kinases. Mol Cell. 2001;8:481-2 pubmed
  37. Diehl S, Bruno R, Wilkinson G, Loose D, Wilting J, Schweigerer L, et al. Altered expression patterns of EphrinB2 and EphB2 in human umbilical vessels and congenital venous malformations. Pediatr Res. 2005;57:537-44 pubmed
    ..Our study shows that the arterial markers ephrin B2 and EphB2 are expressed in a subset of veins, and it remains to be studied whether this is cause or consequence of an altered vascular identity. ..
  38. Birgbauer E, Cowan C, Sretavan D, Henkemeyer M. Kinase independent function of EphB receptors in retinal axon pathfinding to the optic disc from dorsal but not ventral retina. Development. 2000;127:1231-41 pubmed
    ..Thus, while Eph kinase function is involved in RGC axon mapping in the brain, RGC axon pathfinding within the retina is partially mediated by EphB receptors acting in a kinase-independent manner. ..
  39. Lhotak V, Greer P, Letwin K, Pawson T. Characterization of elk, a brain-specific receptor tyrosine kinase. Mol Cell Biol. 1991;11:2496-502 pubmed
    ..The characteristics of the Elk tyrosine kinase suggest that it may be involved in cell-cell interactions in the nervous system. ..
  40. Zhang S, Jiang T, Liang M. Expression of Eph B4 and Ephrin B2 in cervical cancer tissues and angiogenesis. Int J Gynaecol Obstet. 2007;96:46-7 pubmed
  41. Liu X, Liu X, Liu W, Luo M, Tao H, Wu D, et al. HOXA9 transcriptionally regulates the EPHB4 receptor to modulate trophoblast migration and invasion. Placenta. 2017;51:38-48 pubmed publisher
    ..HOXA9 transcriptionally regulated EPHB4 expression to modulate trophoblasts migration and invasion, which may suggest a contribution of HOXA9-EPHB4 in the poor placentation in the pathogenesis of preeclampsia. ..
  42. Kuang S, Bai H, Fang Z, Lopez G, Yang H, Tong W, et al. Aberrant DNA methylation and epigenetic inactivation of Eph receptor tyrosine kinases and ephrin ligands in acute lymphoblastic leukemia. Blood. 2010;115:2412-9 pubmed publisher
    ..These results suggest that epigenetic silencing by hypermethylation of EPH/EPHRIN family genes contributes to ALL pathogenesis and that EPHB4 can function as a tumor suppressor in ALL. ..
  43. Sakamoto H, Zhang X, Suenobu S, Ohbo K, Ogawa M, Suda T. Cell adhesion to ephrinb2 is induced by EphB4 independently of its kinase activity. Biochem Biophys Res Commun. 2004;321:681-7 pubmed
    ..We have shown that EphB4 receptor is expressed in erythroid progenitor and its activation accelerates erythroid differentiation...
  44. Swift M, Weinstein B. Arterial-venous specification during development. Circ Res. 2009;104:576-88 pubmed publisher
  45. Kertesz N, Krasnoperov V, Reddy R, Leshanski L, Kumar S, Zozulya S, et al. The soluble extracellular domain of EphB4 (sEphB4) antagonizes EphB4-EphrinB2 interaction, modulates angiogenesis, and inhibits tumor growth. Blood. 2006;107:2330-8 pubmed
    ..sEphB4 also inhibits tumor growth in murine tumor xenograft models. sEphB4 is thus a therapeutic candidate for vascular proliferative diseases and cancer. ..
  46. Chrencik J, Brooun A, Kraus M, Recht M, Kolatkar A, Han G, et al. Structural and biophysical characterization of the EphB4*ephrinB2 protein-protein interaction and receptor specificity. J Biol Chem. 2006;281:28185-92 pubmed
    Increasing evidence implicates the interaction of the EphB4 receptor with its preferred ligand, ephrinB2, in pathological forms of angiogenesis and in tumorigenesis...
  47. Webler A, Popp R, Korff T, Michaelis U, Urbich C, Busse R, et al. Cytochrome P450 2C9-induced angiogenesis is dependent on EphB4. Arterioscler Thromb Vasc Biol. 2008;28:1123-9 pubmed publisher
    ..Our data indicate that EphB4 is a critical component of the CYP2C9- and 11,12-EET-activated signaling cascade that promotes angiogenesis in vitro as well as in vivo. ..
  48. Masumura T, Yamamoto K, Shimizu N, Obi S, Ando J. Shear stress increases expression of the arterial endothelial marker ephrinB2 in murine ES cells via the VEGF-Notch signaling pathways. Arterioscler Thromb Vasc Biol. 2009;29:2125-31 pubmed publisher
    ..Exposure to shear stress induces an increase in expression of ephrinB2 in murine ES cells via VEGF-Notch signaling pathways. ..
  49. Ciossek T, Lerch M, Ullrich A. Cloning, characterization, and differential expression of MDK2 and MDK5, two novel receptor tyrosine kinases of the eck/eph family. Oncogene. 1995;11:2085-95 pubmed
  50. Zhou X, Suh J, Cerretti D, Zhou R, Dicicco Bloom E. Ephrins stimulate neurite outgrowth during early cortical neurogenesis. J Neurosci Res. 2001;66:1054-63 pubmed
    ..Ephrin systems may induce initial process elaboration by early cortical neurons that is restricted at later stages by well-characterized repulsive signaling mechanisms. ..
  51. Makinen T, Adams R, Bailey J, Lu Q, Ziemiecki A, Alitalo K, et al. PDZ interaction site in ephrinB2 is required for the remodeling of lymphatic vasculature. Genes Dev. 2005;19:397-410 pubmed
    ..Our studies define ephrinB2 as an essential regulator of lymphatic development and indicate that interactions with PDZ domain effectors are required to mediate its functions. ..
  52. Xue C, Huang Z, Wang J, Dong Y, Zhou X. EphrinB2 and EphB4 expression in pterygia: new insights and preliminary results. Can J Ophthalmol. 2009;44:185-8 pubmed publisher
    ..EphrinB2 and EphB4 appear to be overexpressed in pterygium, and they may play important roles in its development. ..
  53. Le Noble F, Moyon D, Pardanaud L, Yuan L, Djonov V, Matthijsen R, et al. Flow regulates arterial-venous differentiation in the chick embryo yolk sac. Development. 2004;131:361-75 pubmed
    ..In conclusion, we show that flow shapes the global patterning of the arterial tree and regulates the activation of the arterial markers ephrinB2 and neuropilin 1...
  54. Xiao H, Bian X, Li Z, Long Z, Wang D. [Detecting protein expression of EphrinB2 ligand and its receptor EphB4 in astrocytoma using confocal laser scanning microscopy]. Ai Zheng. 2004;23:1161-5 pubmed
    ..7, and 53.6+/-18.8). But the green fluorescence intensity of GFAP in SHG-44 cells was 22.3+/-15.3, while in CHG-5 cells was 47.5+/-16.7. Expressions of EphB4 and EphrinB2 proteins may be related to differentiation degree of tumor cells. ..
  55. Pfaff D, Heroult M, Riedel M, Reiss Y, Kirmse R, Ludwig T, et al. Involvement of endothelial ephrin-B2 in adhesion and transmigration of EphB-receptor-expressing monocytes. J Cell Sci. 2008;121:3842-50 pubmed publisher
    ..Collectively, our study identifies a role of EphBR-ephrinB interactions as a new step in the cascade of events leading to monocyte adhesion and transmigration through the vascular endothelium. ..
  56. Kwan Tat S, Pelletier J, Amiable N, Boileau C, Lavigne M, Martel Pelletier J. Treatment with ephrin B2 positively impacts the abnormal metabolism of human osteoarthritic chondrocytes. Arthritis Res Ther. 2009;11:R119 pubmed publisher
    ..b>EphB4 receptor and ephrin B2 levels were determined by quantitative PCR and immunohistochemistry, and the effects of ephrin ..
  57. Zhang G, Zhou J, Fan Q, Zheng Z, Zhang F, Liu X, et al. Arterial-venous endothelial cell fate is related to vascular endothelial growth factor and Notch status during human bone mesenchymal stem cell differentiation. FEBS Lett. 2008;582:2957-64 pubmed publisher
    ..Therefore, differentiation of hMSCs into arterial- or venous-specific ECs depends on VEGF and is regulated by the Notch pathway. ..
  58. Mitchell S, Danca M, Blomgren P, Darrow J, Currie K, Kropf J, et al. Imidazo[1,2-a]pyrazine diaryl ureas: inhibitors of the receptor tyrosine kinase EphB4. Bioorg Med Chem Lett. 2009;19:6991-5 pubmed publisher
    ..Herein we report the discovery and SAR of a novel series of imidazo[1,2-a]pyrazine diarylureas that show nanomolar potency for the EphB4 receptor, in addition to potent activity against several other RTKs.
  59. Salvucci O, De La Luz Sierra M, Martina J, McCormick P, Tosato G. EphB2 and EphB4 receptors forward signaling promotes SDF-1-induced endothelial cell chemotaxis and branching remodeling. Blood. 2006;108:2914-22 pubmed
  60. Kolb P, Caflisch A. Automatic and efficient decomposition of two-dimensional structures of small molecules for fragment-based high-throughput docking. J Med Chem. 2006;49:7384-92 pubmed
    ..DAIM has been successfully used in the in silico screening for inhibitors of beta-secretase and EphB4 kinase by fragment-based high-throughput docking. Possible future applications for de novo ligand design are briefly discussed. ..
  61. Lafleur K, Huang D, Zhou T, Caflisch A, Nevado C. Structure-based optimization of potent and selective inhibitors of the tyrosine kinase erythropoietin producing human hepatocellular carcinoma receptor B4 (EphB4). J Med Chem. 2009;52:6433-46 pubmed publisher
    ..A 45 ns molecular dynamics (MD) simulation of the complex of EphB4 and compound 66 provides further validation of the binding mode obtained by fragment-based docking. ..
  62. Yuuki T, Kanda T, Kishi S. Expression of ephrin in retinal neovascularization and iris rubeosis. J Int Med Res. 2006;34:485-94 pubmed
    ..In the human tissue, ephrin-B2 was detected in two of the five eyes with rubeosis and three of the five eyes with retinal neovascularization. These data suggest that ephrin-B2 is a key regulator of neovascularization. ..
  63. He S, Kumar S, Zhou P, Krasnoperov V, Ryan S, Gill P, et al. Soluble EphB4 inhibition of PDGF-induced RPE migration in vitro. Invest Ophthalmol Vis Sci. 2010;51:543-52 pubmed publisher
    b>EphB4 receptor (EphB4) and its ligand (EphrinB2) play an important role in the regulation of cell adhesion, growth, and migration...
  64. Imondi R, Kaprielian Z. Commissural axon pathfinding on the contralateral side of the floor plate: a role for B-class ephrins in specifying the dorsoventral position of longitudinally projecting commissural axons. Development. 2001;128:4859-71 pubmed
    ..Taken together, these observations suggest that B-class ephrins act locally during a late phase of commissural axon pathfinding to specify the dorsoventral position at which decussated commissural axons turn into the longitudinal axis. ..
  65. Imondi R, Wideman C, Kaprielian Z. Complementary expression of transmembrane ephrins and their receptors in the mouse spinal cord: a possible role in constraining the orientation of longitudinally projecting axons. Development. 2000;127:1397-410 pubmed
    ..Taken together, these data support a possible role for repulsive B-class Eph receptor/ligand interactions in constraining the orientation of longitudinal axon projections at the ventral midline. ..
  66. Pennisi A, Ling W, Li X, Khan S, Shaughnessy J, Barlogie B, et al. The ephrinB2/EphB4 axis is dysregulated in osteoprogenitors from myeloma patients and its activation affects myeloma bone disease and tumor growth. Blood. 2009;114:1803-12 pubmed publisher
    ..Myeloma cells expressed low to undetectable ephrinB2 and EphB4 and did not respond to the chimeric proteins. The ephrinB2/EphB4 axis is dysregulated in MM, and its activation by EphB4-Fc inhibits myeloma growth and bone disease...
  67. Helbling P, Saulnier D, Robinson V, Christiansen J, Wilkinson D, Brändli A. Comparative analysis of embryonic gene expression defines potential interaction sites for Xenopus EphB4 receptors with ephrin-B ligands. Dev Dyn. 1999;216:361-73 pubmed
    ..The expression patterns also suggest that EphB4 receptors and their ligands may be involved in visceral arch formation, somitogenesis, and blood vessel development. ..
  68. Abe T, Kamida T, Fujiki M, Kobayashi H. [Angiogenesis-targeted therapy: therapeutic potential for neurosurgical disorders]. No Shinkei Geka. 2006;34:123-32 pubmed
  69. Kim Y, Hu H, Guevara Gallardo S, Lam M, Fong S, Wang R. Artery and vein size is balanced by Notch and ephrin B2/EphB4 during angiogenesis. Development. 2008;135:3755-64 pubmed publisher
    ..Our findings provide mechanistic insight into the processes underlying artery and vein size equilibration during angiogenesis. ..
  70. Foubert P, Silvestre J, Souttou B, Barateau V, Martin C, Ebrahimian T, et al. PSGL-1-mediated activation of EphB4 increases the proangiogenic potential of endothelial progenitor cells. J Clin Invest. 2007;117:1527-37 pubmed
    ..Therefore, activation of EphB4 is an innovative and potentially valuable therapeutic strategy for improving the recruitment of EPCs to sites of neovascularization and thereby the efficiency of cell-based proangiogenic therapy. ..
  71. Chennakesava C, di Santo S, Ziemiecki A, Schneider H, Andres A. Differential expression of the receptor tyrosine kinase EphB4 and its ligand Ephrin-B2 during human placental development. Placenta. 2006;27:959-67 pubmed
    ..These experiments suggest that EphB4 and ephrin-B2 are instrumental in the establishment of a functional placental structure and of the utero-placental circulation. ..
  72. Freywald A, Sharfe N, Roifman C. The kinase-null EphB6 receptor undergoes transphosphorylation in a complex with EphB1. J Biol Chem. 2002;277:3823-8 pubmed
    ..Our findings demonstrate that EphB6 is an actively signaling receptor that undergoes transphosphorylation upon ligand binding and that can initiate specific cytoplasmic signaling events. ..
  73. Spannuth W, Mangala L, Stone R, Carroll A, Nishimura M, Shahzad M, et al. Converging evidence for efficacy from parallel EphB4-targeted approaches in ovarian carcinoma. Mol Cancer Ther. 2010;9:2377-88 pubmed publisher
    ..001), which likely occur through modulation of phosphoinositide 3-kinase signaling. Collectively, these data identify EphB4 as a valuable therapeutic target in ovarian cancer and offer two new strategies for further development. ..
  74. Cooke J, Moens C, Roth L, Durbin L, Shiomi K, Brennan C, et al. Eph signalling functions downstream of Val to regulate cell sorting and boundary formation in the caudal hindbrain. Development. 2001;128:571-80 pubmed
    ..We propose that Val controls eph expression and that interactions between EphB4a and Ephrin-B2a mediate cell sorting and boundary formation in the segmenting caudal hindbrain. ..
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    ..Additionally, it appears that vascular growth may be modulated in the retina through activation of the PI3K pathway and its downstream components. ..
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    ..Gain of EPHB4 by midgestation spiral arteries may signal completion of pregnancy-induced arterial modification and provide a repulsion mechanism that limits subsequent interactions of the modified vessel with uNK cells and trophoblasts. ..
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    ..EFNB2 gene and EphB4 receptor gene were examined of mRNA specimens in 61 patients with oesophageal squamous cell carcinoma using reverse-..
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    ..Thus, Dll1-mediated Notch activation regulates ephrin-B2 expression and postnatal arteriogenesis. ..
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    ..These data are the first to demonstrate the association of EphB4 with advanced stages of disease and smoking in HNSCC and hence provide a strong rationale for targeting EphB4 for HNSCC therapies. ..