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Receptor tyrosine kinase which binds promiscuously transmembrane ephrin-B family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. Together with its cognate ligand/functional ligand EFNB2 it is involved in the regulation of cell adhesion and migration, and plays a central role in heart morphogenesis, angiogenesis and blood vessel remodeling and permeability. EPHB4-mediated forward signaling controls cellular repulsion and segregation from EFNB2-expressing cells.
Gene References into Functions
miR-454 promotes the proliferation and invasion of trophoblast cells by inhibiting EPHB4 expression. PMID: 30138897
EphB4 expression is associated with colorectal cancer cell proliferation and vascularization. PMID: 29368976
functional expression of EphB4 is considered a promising differentiating characteristic, preferentially determined by non-invasive in vivo imaging, which may improve personalized theranostics of malignant melanoma. PMID: 29462967
The identified endothelial signalling pathway of CCM3-DLL4/Notch-EphB4-Erk1/2 may provide an insight into mechanism of CCM3-ablation-mediated angiogenesis. PMID: 28371279
EphB4 overexpression is associated with resistance to dasatinib in chronic myeloid leukemia. PMID: 29096333
this study uncovered the character of EPHB4-regulating endothelial activation in the pathogenesis of preeclampsia PMID: 27553867
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. PMID: 28292467
EPHB4 mutations were identified in patients with multifocal capillary malformation with arteriovenous malformations. PMID: 28687708
EPHB4 is a critical regulator of early lymphatic vascular development; mutations in the gene can cause an autosomal dominant form of lymphatic-related hydrops fetalis that is associated with a high mortality rate PMID: 27400125
The expression of EPHB4 was increased in gastric cancer and increased EPHB4 expression was correlated with poor survival. Knockdown of EPHB4 promoted adhesion and exerted diverse effects on migration of gastric cancer cells. PMID: 28739744
EphB4 protein acts as a tumour promoter associated with proliferation, invasion, and angiogenesis, and may be used as a potential colorectal cancer (CRC) therapeutic target. PMID: 27072105
Study illustrates that aberrant activation of EphB4/ephrinB2 may mediate chronic myeloid leukemia resistance involved in cytoskeletal proteins. PMID: 27226777
both EphA2 and EphB4 show potential as target for image-guided colorectal cancer surgery, but EphB4 seems to have the best characteristics with respect to tumor/normal mucosa distribution. PMID: 28165374
Enhanced EphB4 expression was significantly associated with Thyroid Lesions. PMID: 26220827
LISA method may be considered rapid and sensitive enough to detect even low levels of total and phosphorylated EphB4 Cost-effectiveness of this method for the detection of differential expression of EphB4 proteins in clinics is also noticeable. PMID: 27072235
EphB4 facilitates stromal-mediated support of hematopoiesis in hematopoietic stem cells. PMID: 26033476
N-(2,4)-dinitrophenyl-L-arginine Interacts with EphB4 and Functions as an EphB4 Kinase Modulator. PMID: 25581780
Stimulation of Eph-B4 function may be a candidate strategy for translation to human clinical trials designed to inhibit venous neointimal hyperplasia. PMID: 25446283
EPHB4 oncogenomic network provides a molecular basis for its role in tumor progression and points to EPHB4 as a potential tumor aggressiveness biomarker and drug target in gastroesophageal cancers PMID: 26414866
Novel EPHB4 receptor tyrosine kinase mutations have been found in lung cancer patients. PMID: 26073592
Suggest role for EphB4/IGF1R signaling in regulation proliferation/migration of breast cancer cells. PMID: 26191333
Results indicate EphB4 receptor as a critical mediator of erythropoietin-induced tumor progression. PMID: 26481148
EphB4 regulates integrin Beta8 expression and integrin Beta8 plays a role in prostate cancer cells. PMID: 25886373
EPHB4 expression is associate with progression of HNSCC from normal tissue to dysplasia and to cancer. PMID: 25391996
Decreased EphB4 expression is associated with acute myeloid leukemia. PMID: 24764074
EphB4 contains two nuclear localization signal sequences and localises to the nucleus. PMID: 25724901
Venous Eph-B4 expression diminished (p = .002), Ephrin-B2 expression was not induced (p = .268), and expression of osteopontin (p = .002) was increased with exposure to arterial magnitudes of shear stress. PMID: 25191151
Silencing of EPHB4 significantly reduced the transmigration of synovial sarcoma cells. PMID: 25274141
our study revealed the important function and regulation of EphB4 in the progression of ESCC and suggested EphB4 as a novel target for the treatment of ESCC. PMID: 24771266
The recombinant plasmid can inhibit the expression of EphB4 mRNA and protein in PANC-1 cells, as well as cell growth and migration. PMID: 25051915
levels of EphB4, mTOR and Akt were distinctly lower than those in other groups. It was concluded that suppression of EphB4 may inhibit the growth of ovarian cancer cells by downregulation of the PI3K/Akt/mTOR pathway. PMID: 22684558
EphB4 activation can differentially inhibit breast cancer cells at post confluent state. PMID: 24427781
High EphB4 expression is associated with glioma. PMID: 24121831
These results are the first to identify EphB4 and its cross-talk with PDGFRbeta as unexpected vital determinants of tumor cell survival in alveolar rhabdomyosarcoma. PMID: 24733895
Our data suggests EphB4 as an upstream regulator of ER-alpha in human breast cancer cells by modulating ER-alpha transcription. The results also suggest Akt as a relevant downstream signaling molecule in this novel EphB4-ER-alpha pathway. PMID: 23725356
The EphB4 receptor tyrosine kinase promotes lung cancer growth. PMID: 23844053
EphB4 was overexpressed in 72% of mesothelioma tissues PMID: 23721559
Compared gene expression profiles in CRC patients treated with bevacizumab who responded to the treatment with those that did not respond. Found EPHB4 expression significantly increased in nonresponders and high levels associated with decreased survival. PMID: 23579861
HAb47-Cy5.5 successfully imaged the decreased EphB4 expression. PMID: 23211050
Data indicate that the reduced vimentin expression in response to EPHB4, WIPF2 and MTHFD2 silencing was observed at mRNA and protein levels. PMID: 23295955
molecular classification of breast cancer is based upon the expression of ESR, PGR and HER2; the expression of EPOR, membrane receptor GPER and EPHB4 may be considered as an additional classification factor in breast cancer PMID: 23314808
EphB4 receptor expresion is correlated to the initiation, progression and tumor angiogenesis. PMID: 23079712
verify amplification and/or deletion in the ACHE, BCHE, EPHB4 and MME genes in 32 samples of sporadic breast cancer PMID: 23063927
expression of EphB4 was significantly upregulated in clinical glioma samples; overexpression of EphB4 in glioma cell lines accelerated cell growth and tumorigenesis; downregulation of EphB4 inhibited cell growth PMID: 23138393
EphB4 is robustly expressed and potentially serves as a novel biomarker for targeted therapy in esophageal cancers PMID: 23100466
EphB4 plays an important role in the progression of papillary thyroid carcinoma by stimulating cell migration and EphB4 might be a potential therapeutic target in papillary thyroid carcinoma. PMID: 22528941
EphB4 protein expression is significantly increased in non-small- cell lung cancer and corresponds to progression and severity of the disease. PMID: 22684742
EphB4/EphrinB2 expression has closed related to gennesis and progression of hepatoblastoma. PMID: 22024229
High EphB4 is associated with malignant urogenital tissue. PMID: 19272799
Ephb4 was over-expressed and localized to the cytoplasm of gastric cancer cells. Moreover, Ephb4 protein was observed as being significantly related to tumor size and regional lymph nodes category. PMID: 20686847
Cell membrane; Single-pass type I membrane protein.
Protein Families
Protein kinase superfamily, Tyr protein kinase family, Ephrin receptor subfamily
Tissue Specificity
Abundantly expressed in placenta but also detected in kidney, liver, lung, pancreas, skeletal muscle and heart. Expressed in primitive and myeloid, but not lymphoid, hematopoietic cells. Also observed in cell lines derived from liver, breast, colon, lung,