Gene Symbol: Ephb4
Description: Eph receptor B4
Alias: AI042935, Htk, MDK2, Myk1, Tyro11, b2b2412Clo, ephrin type-B receptor 4, developmental kinase 2, hepatoma transmembrane kinase, mDK-2, tyrosine kinase MYK-1
Species: mouse
Products:     Ephb4

Top Publications

  1. Lavine K, Long F, Choi K, Smith C, Ornitz D. Hedgehog signaling to distinct cell types differentially regulates coronary artery and vein development. Development. 2008;135:3161-71 pubmed publisher
    ..Finally, we present evidence suggesting that coronary arteries and veins may be derived from distinct lineages. ..
  2. Wang H, Chen Z, Anderson D. Molecular distinction and angiogenic interaction between embryonic arteries and veins revealed by ephrin-B2 and its receptor Eph-B4. Cell. 1998;93:741-53 pubmed
    ..These results provide evidence that differences between arteries and veins are in part genetically determined and suggest that reciprocal signaling between these two types of vessels is crucial for morphogenesis of the capillary beds. ..
  3. Raft S, Andrade L, Shao D, Akiyama H, Henkemeyer M, Wu D. Ephrin-B2 governs morphogenesis of endolymphatic sac and duct epithelia in the mouse inner ear. Dev Biol. 2014;390:51-67 pubmed publisher
    ..We propose that developmental dysplasias described here are a gene dose-sensitive cause of the vestibular dysfunction observed in EphB-Efnb2 signaling-deficient mice. ..
  4. Wu B, Zhang Z, Lui W, Chen X, Wang Y, Chamberlain A, et al. Endocardial cells form the coronary arteries by angiogenesis through myocardial-endocardial VEGF signaling. Cell. 2012;151:1083-96 pubmed publisher
    ..This information may help develop better cell therapies for coronary artery disease...
  5. 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
    ..We postulated that activation of the EphB4/ephrin-B2 system may enhance EPC proangiogenic potential...
  6. Duarte A, Hirashima M, Benedito R, Trindade A, Diniz P, Bekman E, et al. Dosage-sensitive requirement for mouse Dll4 in artery development. Genes Dev. 2004;18:2474-8 pubmed
    ..This implicates Dll4 as the specific mammalian endothelial ligand for autocrine endothelial Notch signaling, and suggests that Dll4 may be a suitable target for intervention in arterial angiogenesis. ..
  7. Adams R, Wilkinson G, Weiss C, Diella F, Gale N, Deutsch U, et al. Roles of ephrinB ligands and EphB receptors in cardiovascular development: demarcation of arterial/venous domains, vascular morphogenesis, and sprouting angiogenesis. Genes Dev. 1999;13:295-306 pubmed
  8. Red Horse K, Ueno H, Weissman I, Krasnow M. Coronary arteries form by developmental reprogramming of venous cells. Nature. 2010;464:549-53 pubmed publisher
    ..Understanding this new reprogramming process and identifying the endogenous signals should suggest more natural ways of engineering coronary bypass grafts and revascularizing the heart. ..
  9. Van Den Akker N, Caolo V, Wisse L, Peters P, Poelmann R, Carmeliet P, et al. Developmental coronary maturation is disturbed by aberrant cardiac vascular endothelial growth factor expression and Notch signalling. Cardiovasc Res. 2008;78:366-75 pubmed
    ..This knowledge can contribute to optimizing therapies targeting VEGF signalling by enabling balancing between angiogenesis and vascular maturation. ..

More Information


  1. Seo S, Fujita H, Nakano A, Kang M, Duarte A, Kume T. The forkhead transcription factors, Foxc1 and Foxc2, are required for arterial specification and lymphatic sprouting during vascular development. Dev Biol. 2006;294:458-70 pubmed
    ..Taken together, our results demonstrate that Foxc transcription factors are novel regulators of arterial cell specification upstream of Notch signaling and lymphatic sprouting during embryonic development. ..
  2. You L, Lin F, Lee C, DeMayo F, Tsai M, Tsai S. Suppression of Notch signalling by the COUP-TFII transcription factor regulates vein identity. Nature. 2005;435:98-104 pubmed
    ..Thus, COUP-TFII has a critical role in repressing Notch signalling to maintain vein identity, which suggests that vein identity is under genetic control and is not derived by a default pathway. ..
  3. Corada M, Nyqvist D, Orsenigo F, Caprini A, Giampietro C, Taketo M, et al. The Wnt/beta-catenin pathway modulates vascular remodeling and specification by upregulating Dll4/Notch signaling. Dev Cell. 2010;18:938-49 pubmed publisher
    ..We propose that early and sustained beta-catenin signaling prevents correct endothelial cell differentiation, altering vascular remodeling and arteriovenous specification. ..
  4. Wang Y, Nakayama M, Pitulescu M, Schmidt T, Bochenek M, Sakakibara A, et al. Ephrin-B2 controls VEGF-induced angiogenesis and lymphangiogenesis. Nature. 2010;465:483-6 pubmed publisher
    ..Our results show that full VEGFR3 signalling is coupled to receptor internalization. Ephrin-B2 is a key regulator of this process and thereby controls angiogenic and lymphangiogenic growth. ..
  5. Trindade A, Kumar S, Scehnet J, Lopes da Costa L, Becker J, Jiang W, et al. Overexpression of delta-like 4 induces arterialization and attenuates vessel formation in developing mouse embryos. Blood. 2008;112:1720-9 pubmed publisher
    ..These results establish the role of Dll4 in arterial identity determination, and regulation of angiogenesis subject to dose and location. ..
  6. Erber R, Eichelsbacher U, Powajbo V, Korn T, Djonov V, Lin J, et al. EphB4 controls blood vascular morphogenesis during postnatal angiogenesis. EMBO J. 2006;25:628-41 pubmed
    ..we demonstrate that endothelial cells of human malignant brain tumors also express guidance molecules, such as EphB4 and its ligand ephrinB2...
  7. Foo S, Turner C, Adams S, Compagni A, Aubyn D, Kogata N, et al. Ephrin-B2 controls cell motility and adhesion during blood-vessel-wall assembly. Cell. 2006;124:161-73 pubmed
    ..Our results indicate that the role of ephrin-B2 and EphB receptors in these processes involves Crk-p130(CAS) signaling and suggest that ephrin-B2 has some cell-cell-contact-independent functions. ..
  8. Gerety S, Wang H, Chen Z, Anderson D. Symmetrical mutant phenotypes of the receptor EphB4 and its specific transmembrane ligand ephrin-B2 in cardiovascular development. Mol Cell. 1999;4:403-14 pubmed
    ..Here we show that EphB4, a specific receptor for ephrin-B2, is exclusively expressed by vascular endothelial cells in embryos and is ..
  9. Zovein A, Luque A, Turlo K, Hofmann J, Yee K, Becker M, et al. Beta1 integrin establishes endothelial cell polarity and arteriolar lumen formation via a Par3-dependent mechanism. Dev Cell. 2010;18:39-51 pubmed publisher
    ..Combined, our findings demonstrate that beta1 integrin functions upstream of Par3 as part of a molecular cascade required for endothelial cell polarity and lumen formation. ..
  10. Baumer S, Keller L, Holtmann A, Funke R, August B, Gamp A, et al. Vascular endothelial cell-specific phosphotyrosine phosphatase (VE-PTP) activity is required for blood vessel development. Blood. 2006;107:4754-62 pubmed
    ..No signs for enhanced endothelial apoptosis or proliferation were observed. Thus, the activity of VE-PTP is not required for the initial formation of blood vessels, yet it is essential for their maintenance and remodeling. ..
  11. Xu K, Sacharidou A, Fu S, Chong D, Skaug B, Chen Z, et al. Blood vessel tubulogenesis requires Rasip1 regulation of GTPase signaling. Dev Cell. 2011;20:526-39 pubmed publisher
    ..This study identifies Rasip1 as a unique, endothelial-specific regulator of Rho GTPase signaling, which is essential for blood vessel morphogenesis. ..
  12. Murphy P, Kim T, Lu G, Bollen A, Schaffer C, Wang R. Notch4 normalization reduces blood vessel size in arteriovenous malformations. Sci Transl Med. 2012;4:117ra8 pubmed publisher
    ..This regression was initiated by vessel narrowing without the loss of ECs and required restoration of EphB4 receptor expression by venous ECs...
  13. Hall Glenn F, De Young R, Huang B, Van Handel B, Hofmann J, Chen T, et al. CCN2/connective tissue growth factor is essential for pericyte adhesion and endothelial basement membrane formation during angiogenesis. PLoS ONE. 2012;7:e30562 pubmed publisher
  14. Wilson M, Riemer C, Martindale D, Schnupf P, Boright A, Cheung T, et al. Comparative analysis of the gene-dense ACHE/TFR2 region on human chromosome 7q22 with the orthologous region on mouse chromosome 5. Nucleic Acids Res. 2001;29:1352-65 pubmed
    ..an open reading frame flanked by ACHE: and Asr2, a novel cation-chloride cotransporter interacting protein Cip1, Ephb4, Zan and Perq1...
  15. Kuhnert F, Mancuso M, Shamloo A, Wang H, Choksi V, Florek M, et al. Essential regulation of CNS angiogenesis by the orphan G protein-coupled receptor GPR124. Science. 2010;330:985-9 pubmed publisher
    ..Further, the functional tropism of GPR124 marks this receptor as a therapeutic target for CNS-related vascular pathologies. ..
  16. Böhmer R, Neuhaus B, Bühren S, Zhang D, Stehling M, Böck B, et al. Regulation of developmental lymphangiogenesis by Syk(+) leukocytes. Dev Cell. 2010;18:437-49 pubmed publisher
    ..This mechanism does not involve circulating endothelial progenitor cells and demonstrates the potential of hematopoietic cells to control developmental lymphangiogenesis. ..
  17. Deng Y, Larrivee B, Zhuang Z, Atri D, Moraes F, Prahst C, et al. Endothelial RAF1/ERK activation regulates arterial morphogenesis. Blood. 2013;121:3988-96, S1-9 pubmed publisher
    ..Our results suggest that endothelial ERK signaling is critical for both arteriogenesis and arterial-venous patterning and that RAF1 Ser(259) phosphorylation plays a critical role in preventing unopposed ERK activation. ..
  18. Chu M, Li T, Shen B, Cao X, Zhong H, Zhang L, et al. Angiopoietin receptor Tie2 is required for vein specification and maintenance via regulating COUP-TFII. elife. 2016;5: pubmed publisher
    ..Together, our results imply that Tie2 is essential for venous specification and maintenance via Akt mediated stabilization of COUP-TFII. ..
  19. Gale N, Yancopoulos G. Growth factors acting via endothelial cell-specific receptor tyrosine kinases: VEGFs, angiopoietins, and ephrins in vascular development. Genes Dev. 1999;13:1055-66 pubmed
  20. Zhang J, Dong H, Wang B, Zhu S, Croy B. Dynamic changes occur in patterns of endometrial EFNB2/EPHB4 expression during the period of spiral arterial modification in mice. Biol Reprod. 2008;79:450-8 pubmed publisher
    ..Antibodies to EFNB2, EPHB4, and LYVE1, respectively, identified arterial, venous, and lymphatic endothelia...
  21. Raft S, Coate T, Kelley M, Crenshaw E, Wu D. Pou3f4-mediated regulation of ephrin-b2 controls temporal bone development in the mouse. PLoS ONE. 2014;9:e109043 pubmed publisher
    ..We propose that Efnb2 is a target of Pou3f4 transcription factor activity and an effector of mesenchymal patterning during temporal bone development. ..
  22. 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
    ..Loss of ephrin B2 or its receptor EphB4 also leads to enlarged aortae and underdeveloped cardinal veins; however, endothelial cells with venous identity ..
  23. Egawa G, Osawa M, Uemura A, Miyachi Y, Nishikawa S. Transient expression of ephrin b2 in perinatal skin is required for maintenance of keratinocyte homeostasis. J Invest Dermatol. 2009;129:2386-95 pubmed publisher
  24. Andres A, Reid H, Zurcher G, Blaschke R, Albrecht D, Ziemiecki A. Expression of two novel eph-related receptor protein tyrosine kinases in mammary gland development and carcinogenesis. Oncogene. 1994;9:1461-7 pubmed
    ..These results indicate that myk-1 and myk-2 expression is induced during the proliferation of the mammary gland and down-regulated by its differentiation. ..
  25. Tischfield M, Robson C, Gilette N, Chim S, Sofela F, DeLisle M, et al. Cerebral Vein Malformations Result from Loss of Twist1 Expression and BMP Signaling from Skull Progenitor Cells and Dura. Dev Cell. 2017;42:445-461.e5 pubmed publisher
  26. Benson M, Opperman L, Westerlund J, Fernandez C, San Miguel S, Henkemeyer M, et al. Ephrin-B stimulation of calvarial bone formation. Dev Dyn. 2012;241:1901-10 pubmed publisher
    Ephrin-B2 on osteoclasts was reported to promote bone formation as part of homeostasis by activating the EphB4 tyrosine kinase receptor on osteoblasts...
  27. Luxey M, Laussu J, Jungas T, Davy A. Generation of transgenic mice overexpressing EfnB2 in endothelial cells. Genesis. 2011;49:811-20 pubmed publisher
    Genetic studies have shown that ephrin-B2 and its cognate EphB4 receptor are necessary for normal embryonic angiogenesis...
  28. Liebl J, Zhang S, Moser M, Agalarov Y, Demir C, Hager B, et al. Cdk5 controls lymphatic vessel development and function by phosphorylation of Foxc2. Nat Commun. 2015;6:7274 pubmed publisher
    ..Collectively, our findings show that Cdk5-Foxc2 interaction represents a critical regulator of lymphatic vessel development and the transcriptional network underlying lymphatic vascular remodeling. ..
  29. Yang C, Guo Y, Jadlowiec C, Li X, Lv W, Model L, et al. Vascular endothelial growth factor-A inhibits EphB4 and stimulates delta-like ligand 4 expression in adult endothelial cells. J Surg Res. 2013;183:478-86 pubmed publisher
    ..EC, wild type (EphB4+/+) or heterozygous knockout (EphB4+/-), were stimulated with VEGF-A (0-100 ng/mL) and examined with quantitative ..
  30. Xue C, Zhang T, Xie X, Zhang Q, Zhang S, Zhu B, et al. Substrate stiffness regulates arterial-venous differentiation of endothelial progenitor cells via the Ras/Mek pathway. Biochim Biophys Acta Mol Cell Res. 2017;1864:1799-1808 pubmed publisher
    ..arterial endothelial cell marker ephrinB2 were found to increase, while the expression of the venous marker EphB4 decreased. Further experiments were performed to identify the mechanotransduction pathway involved in this process...
  31. Protack C, Foster T, Hashimoto T, Yamamoto K, Lee M, Kraehling J, et al. Eph-B4 regulates adaptive venous remodeling to improve arteriovenous fistula patency. Sci Rep. 2017;7:15386 pubmed publisher
    ..Inhibition of Akt1 function abolishes Eph-B-mediated venous remodeling suggesting that Eph-B4 regulates AVF venous adaptation through an Akt1-mediated mechanism. ..
  32. 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. ..
  33. Lu X, Le Noble F, Yuan L, Jiang Q, de Lafarge B, Sugiyama D, et al. The netrin receptor UNC5B mediates guidance events controlling morphogenesis of the vascular system. Nature. 2004;432:179-86 pubmed
    ..Netrin-1 causes endothelial filopodial retraction, but only when UNC5B is present. Thus, UNC5B functions as a repulsive netrin receptor in endothelial cells controlling morphogenesis of the vascular system. ..
  34. van Eyll J, Passante L, Pierreux C, Lemaigre F, Vanderhaeghen P, Rousseau G. Eph receptors and their ephrin ligands are expressed in developing mouse pancreas. Gene Expr Patterns. 2006;6:353-9 pubmed
    ..We conclude that specific members of the Eph/ephrin family are expressed in embryonic pancreas according to a dynamic temporal and regional pattern. ..
  35. Bovenkamp D, Greer P. Degenerate PCR-based cloning method for Eph receptors and analysis of their expression in the developing murine central nervous system and vasculature. DNA Cell Biol. 2001;20:203-13 pubmed
    ..These results suggest a role for both EphA and EphB receptors in vascular development. ..
  36. Munger S, Geng X, Srinivasan R, Witte M, Paul D, Simon A. Segregated Foxc2, NFATc1 and Connexin expression at normal developing venous valves, and Connexin-specific differences in the valve phenotypes of Cx37, Cx43, and Cx47 knockout mice. Dev Biol. 2016;412:173-90 pubmed publisher
    ..The partition of Foxc2 and NFATc1 expression at VV leaflets makes it unlikely that these factors directly cooperate during the leaflet elongation stage of VV development. ..
  37. Nielsen C, Cuervo H, Ding V, Kong Y, Huang E, Wang R. Deletion of Rbpj from postnatal endothelium leads to abnormal arteriovenous shunting in mice. Development. 2014;141:3782-92 pubmed publisher
    ..After AV shunts had formed, whole-mount immunostaining showed decreased Efnb2 and increased Ephb4 expression within AV shunts, suggesting that ECs were reprogrammed from arterial to venous identity...
  38. Aslam M, Abraham J, Mansoor A, Druker B, Tyner J, Keller C. PDGFR? reverses EphB4 signaling in alveolar rhabdomyosarcoma. Proc Natl Acad Sci U S A. 2014;111:6383-8 pubmed publisher
    ..We identified ephrin receptor B4 (EphB4) as a target that is widely expressed in human aRMS and that portends a poor clinical outcome in an expression ..
  39. Lange A, Haitchi H, Lecras T, Sridharan A, Xu Y, Wert S, et al. Sox17 is required for normal pulmonary vascular morphogenesis. Dev Biol. 2014;387:109-20 pubmed publisher
    ..The severity of the postnatal cardiac phenotype was correlated with the severity of pulmonary vasculature abnormalities. Sox17 is required for normal formation of the pulmonary vasculature and postnatal cardiovascular homeostasis. ..
  40. 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
    Cell to cell interaction in bone marrow is crucial for differentiation of hematopoietic cells. We have shown that EphB4 receptor is expressed in erythroid progenitor and its activation accelerates erythroid differentiation...
  41. Chintala H, Krupska I, Yan L, LAU L, Grant M, Chaqour B. The matricellular protein CCN1 controls retinal angiogenesis by targeting VEGF, Src homology 2 domain phosphatase-1 and Notch signaling. Development. 2015;142:2364-74 pubmed publisher
    ..These data highlight novel functions of CCN1 as a naturally optimized molecule, fine-controlling key processes in physiological angiogenesis and safeguarding against aberrant angiogenic responses. ..
  42. Chen K, Bai H, Liu Y, Hoyle D, Shen W, Wu L, et al. EphB4 forward-signaling regulates cardiac progenitor development in mouse ES cells. J Cell Biochem. 2015;116:467-75 pubmed publisher
    ..Bidirectional signaling of EphB4-ephrinB2 regulates cardiovascular development...
  43. Ren X, Ustiyan V, Pradhan A, Cai Y, Havrilak J, Bolte C, et al. FOXF1 transcription factor is required for formation of embryonic vasculature by regulating VEGF signaling in endothelial cells. Circ Res. 2014;115:709-20 pubmed publisher
    ..FOXF1 is required for the formation of embryonic vasculature by regulating endothelial genes critical for vascular development and vascular endothelial growth factor signaling. ..
  44. Cortegano I, Melgar Rojas P, Luna Zurita L, Siguero Álvarez M, Marcos M, Gaspar M, et al. Notch1 regulates progenitor cell proliferation and differentiation during mouse yolk sac hematopoiesis. Cell Death Differ. 2014;21:1081-94 pubmed publisher
    ..5 embryos and demonstrate that Notch signaling regulates this process by balancing the proliferation and differentiation dynamics of lineage-restricted intermediate progenitors. ..
  45. Majima T, Takeuchi K, Sano K, Hirashima M, Zankov D, Tanaka Okamoto M, et al. An Adaptor Molecule Afadin Regulates Lymphangiogenesis by Modulating RhoA Activity in the Developing Mouse Embryo. PLoS ONE. 2013;8:e68134 pubmed publisher
    ..These results indicate that afadin has different effects on blood and lymphatic endothelial cells by controlling the levels of RhoA activation, which may critically regulate the lymphangiogenesis of mouse embryos. ..
  46. Katsuta H, Fukushima Y, Maruyama K, Hirashima M, Nishida K, Nishikawa S, et al. EphrinB2-EphB4 signals regulate formation and maintenance of funnel-shaped valves in corneal lymphatic capillaries. Invest Ophthalmol Vis Sci. 2013;54:4102-8 pubmed publisher
    To elucidate the role of signals mediated by EphB4 receptor tyrosine kinase and its transmembrane ephrinB2 ligand in corneal lymphatic capillaries...
  47. Djokovic D, Trindade A, Gigante J, Badenes M, Silva L, Liu R, et al. Combination of Dll4/Notch and Ephrin-B2/EphB4 targeted therapy is highly effective in disrupting tumor angiogenesis. BMC Cancer. 2010;10:641 pubmed publisher
    Dll4/Notch and Ephrin-B2/EphB4 pathways play critical roles in tumor vessel development and maturation...
  48. 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
    ..Because EphB4 is involved in vascular development, the aim of this study was to investigate whether, and to what extent, EphB4 ..
  49. 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...
  50. Shen L, Zhang L, Wang L, Zhou R, Yang C, Zhang J, et al. Disturbed Expression of EphB4, but Not EphrinB2, Inhibited Bone Regeneration in an In Vivo Inflammatory Microenvironment. Mediators Inflamm. 2016;2016:6430407 pubmed publisher
    The important role of ephrinB2-EphB4 signaling pathway in bone remodeling has been well established...
  51. Chen C, Bertozzi C, Zou Z, Yuan L, Lee J, Lu M, et al. Blood flow reprograms lymphatic vessels to blood vessels. J Clin Invest. 2012;122:2006-17 pubmed publisher
    ..These findings reveal that blood flow can convert lymphatic vessels to blood vessels, demonstrating that hemodynamic forces may reprogram endothelial and vessel identity in cardiovascular diseases associated with abnormal flow. ..
  52. Islam S, Loizides A, Fialkovich J, Grand R, Montgomery R. Developmental expression of Eph and ephrin family genes in mammalian small intestine. Dig Dis Sci. 2010;55:2478-88 pubmed publisher
    ..Most were uniformly expressed. In contrast, levels of EphA4, EphA8, EphB4, and ephrin-B2 messenger RNA (mRNA) were highest during early fetal development and declined with age...
  53. Lindskog H, Kim Y, Jelin E, Kong Y, Guevara Gallardo S, Kim T, et al. Molecular identification of venous progenitors in the dorsal aorta reveals an aortic origin for the cardinal vein in mammals. Development. 2014;141:1120-8 pubmed publisher
    ..These ECs, expressing the venous molecular markers Coup-TFII and EphB4, cohabited the early DA with ECs expressing the arterial molecular markers ephrin B2, Notch and connexin 40...
  54. Wang M, Collins M, Foster T, Bai H, Hashimoto T, Santana J, et al. Eph-B4 mediates vein graft adaptation by regulation of endothelial nitric oxide synthase. J Vasc Surg. 2017;65:179-189 pubmed publisher
    ..05). eNOS is a mediator of vein graft adaptation to the arterial environment. Eph-B4 stimulates eNOS phosphorylation in vitro and may mediate vein graft adaptation by regulation of eNOS activity in vivo. ..
  55. Villasenor A, Marty Santos L, Dravis C, Fletcher P, Henkemeyer M, Cleaver O. EphB3 marks delaminating endocrine progenitor cells in the developing pancreas. Dev Dyn. 2012;241:1008-19 pubmed publisher
    ..Together, these data introduce EphB3 as a new biomarker to identify beta-cells at a critical step during their step-wise differentiation and define the timeframe of endocrine differentiation. ..
  56. Lewis A, Hwa J, Wang R, Soriano P, Bush J. Neural crest defects in ephrin-B2 mutant mice are non-autonomous and originate from defects in the vasculature. Dev Biol. 2015;406:186-95 pubmed publisher
    ..Together, these data indicate that direct ephrin-B2 signaling to NCCs is not required for NCC guidance, which instead depends on proper organization of the embryonic vasculature. ..
  57. Cowan C, Yokoyama N, Bianchi L, Henkemeyer M, Fritzsch B. EphB2 guides axons at the midline and is necessary for normal vestibular function. Neuron. 2000;26:417-30 pubmed
    ..This suggests EphB2 may regulate ionic homeostasis and endolymph fluid production through macromolecular associations with membrane channels that transport chloride, bicarbonate, and water. ..
  58. Arthur A, Panagopoulos R, Cooper L, Menicanin D, Parkinson I, Codrington J, et al. EphB4 enhances the process of endochondral ossification and inhibits remodeling during bone fracture repair. J Bone Miner Res. 2013;28:926-35 pubmed publisher
    Previous reports have identified a role for the tyrosine kinase receptor EphB4 and its ligand, ephrinB2, as potential mediators of both bone formation by osteoblasts and bone resorption by osteoclasts...
  59. Luo H, Yu G, Tremblay J, Wu J. EphB6-null mutation results in compromised T cell function. J Clin Invest. 2004;114:1762-73 pubmed
    ..Further downstream, in the absence of EphB6, ZAP-70 activation, LAT phosphorylation, the association of PLCgamma1 with SLP-76, and p44/42 MAPK activation were diminished. Thus, we have shown that EphB6 is pivotal in T cell function. ..
  60. Krebs L, Starling C, Chervonsky A, Gridley T. Notch1 activation in mice causes arteriovenous malformations phenocopied by ephrinB2 and EphB4 mutants. Genesis. 2010;48:146-50 pubmed publisher
    ..Surprisingly, embryos homozygous for mutations of the ephrinB/EphB pathway genes Efnb2 and Ephb4 exhibit vascular defects and arteriovenous malformations that phenocopy the Notch1 gain of function mutants...
  61. Wang Y, Thorin E, Luo H, Tremblay J, Lavoie J, Wu Z, et al. EPHB4 Protein Expression in Vascular Smooth Muscle Cells Regulates Their Contractility, and EPHB4 Deletion Leads to Hypotension in Mice. J Biol Chem. 2015;290:14235-44 pubmed publisher
    ..This work presents evidence that EPHB4 on vascular smooth muscle cells (VSMCs) is involved in blood pressure regulation...
  62. Lavine K, Kovacs A, Ornitz D. Hedgehog signaling is critical for maintenance of the adult coronary vasculature in mice. J Clin Invest. 2008;118:2404-14 pubmed publisher
    ..Together, these data demonstrate that HH signaling is essential for cardiac function at the level of the coronary vasculature and caution against the use of HH antagonists in patients with prior or ongoing heart disease. ..
  63. 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
    ..that osteoclasts express the NFATc1 target gene Efnb2 (encoding ephrinB2), while osteoblasts express the receptor EphB4, along with other ephrin-Eph family members...
  64. Wnuk M, Hlushchuk R, Janot M, Tuffin G, Martiny Baron G, Holzer P, et al. Podocyte EphB4 signaling helps recovery from glomerular injury. Kidney Int. 2012;81:1212-25 pubmed publisher
    ..1 nephritis in rats. EphB4 and ephrinBs were expressed in healthy glomerular podocytes and were upregulated during Thy1...
  65. Han D, Jeon S, Sohn D, Lee C, Ahn S, Kim W, et al. SRG3, a core component of mouse SWI/SNF complex, is essential for extra-embryonic vascular development. Dev Biol. 2008;315:136-46 pubmed publisher
    ..However, in Srg3-/-Tg+ yolk sacs, the visceral endoderm did not develop normally. Our results indicate that SRG3 is required for angiogenesis and visceral endoderm development in the yolk sac. ..
  66. Hamada K, Oike Y, Ito Y, Maekawa H, Miyata K, Shimomura T, et al. Distinct roles of ephrin-B2 forward and EphB4 reverse signaling in endothelial cells. Arterioscler Thromb Vasc Biol. 2003;23:190-7 pubmed
    The transmembrane ligand ephrin-B2 and its receptor tyrosine kinase EphB4 are specifically expressed on arterial and venous endothelial cells, respectively, and bidirectional signals mediated by both proteins play an important role in ..
  67. Davis R, Curtis C, Griffin C. BRG1 promotes COUP-TFII expression and venous specification during embryonic vascular development. Development. 2013;140:1272-81 pubmed publisher
    ..This study provides the first description of a factor promoting COUP-TFII expression in vascular endothelium and highlights a novel role for chromatin remodeling in venous specification. ..
  68. Visconti R, Richardson C, Sato T. Orchestration of angiogenesis and arteriovenous contribution by angiopoietins and vascular endothelial growth factor (VEGF). Proc Natl Acad Sci U S A. 2002;99:8219-24 pubmed
    ..We believe that our study is a step toward understanding how multiple classes of factors harmonize angiogenesis and blood vessel types. ..
  69. Hatch J, Mukouyama Y. Spatiotemporal mapping of vascularization and innervation in the fetal murine intestine. Dev Dyn. 2015;244:56-68 pubmed publisher
    ..These studies provide useful anatomical data for continuing investigations on the functional mechanisms underlying intestinal organogenesis. ..
  70. Wilkinson G, Schittny J, Reinhardt D, Klein R. Role for ephrinB2 in postnatal lung alveolar development and elastic matrix integrity. Dev Dyn. 2008;237:2220-34 pubmed publisher
    ..Postnatal day 1 mutant lungs show extracellular matrix alterations without differences in proportions of major distal cell populations. We conclude that lung alveolar formation relies on endothelial ephrinB2 function. ..
  71. Muto A, Yi T, Harrison K, Davalos A, Fancher T, Ziegler K, et al. Eph-B4 prevents venous adaptive remodeling in the adult arterial environment. J Exp Med. 2011;208:561-75 pubmed publisher
    ..Eph-B4-Cav-1-mediated vessel remodeling may be a venous-specific adaptive mechanism. Controlled stimulation of embryonic signaling pathways such as Eph-B4 may be a novel strategy to manipulate venous wall remodeling in adults. ..
  72. Kaenel P, Hahnewald S, Wotzkow C, Strange R, Andres A. Overexpression of EphB4 in the mammary epithelium shifts the differentiation pathway of progenitor cells and promotes branching activity and vascularization. Dev Growth Differ. 2014;56:255-75 pubmed publisher
    ..We have previously shown that epithelial overexpression of the EphB4 receptor results in defective mammary epithelial development and conferred a metastasizing tumor phenotype on ..
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