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blockage of EphA4/ephrin signaling between neuron and microglia decreased in oxygen-glucose deprivation and reperfusion -induced injury by promoting alternative activation of microglia via RhoA/ROCK2 signaling.
our data revealed a strong association between high EPHA4 expression and advanced tumor stage, aggressive BLBC molecular subtype and poor prognosis. Importantly, we found significant co-expression of EPHA4 and the TGFbeta receptor type-2 (TGFbetaR2) in breast cancer subtypes associated with increased tumor relapse and drug resistance.
Taken together, these results identify EphA4 as a new entry receptor for Kaposi's sarcoma-associated herpesvirus.
MiR-519d down-regulates EphA4 expression in melanoma.
These findings confirmed that EphA4 is a direct target gene of miR-335 and that miR-335 suppresses breast cancer cell proliferation and motility in part by directly inhibiting EphA4 expression.
Therefore EphA4 is an emerging AbetaOs receptor and the activation of the EphA4/c-Abl axis would explain the synaptic spine alterations found in Alzheimer's disease.
High erythropoietin-producing hepatocellular carcinoma receptor A (EphA) 1, 2, and 4 expression levels were significantly related to recurrence.
These results demonstrate a novel role for SORLA as a physiological and pathological EphA4 modulator.
The expression of both EphA4-FL and EphA4-N was significantly higher in the nervous tissue of SOD1(G93A) compared to wild-type mice suggesting that both forms are modulated during the disease process.
the PI3K/AKT, Wnt/beta-catenin signaling pathways as well as ERK1/2 downstream of EPHA4 receptor activation, play an important role in the regulation of events related with the EMT development, which may be associated with the therapeutic failure in rectal cancer after radiotherapy.
Molecular interactions of EphA4, growth hormone receptor, Jak2, and STAT5B have been described.
Findings demonstrated that mutant alpha2-chimaerin and EphA4 have different genetic interactions in distinct motor neuron pools: abducens neurons use bidirectional ephrin signaling via mutant alpha2-chimaerin to direct growth, while cervical spinal neurons use only ephrin forward signaling
Reduced EphA4 expression is associated with EBV-associated B lymphoma.
No difference was found in the expression of EPHA4 in morphologically normal glands, HGPIN, or prostatic cancer.
we supposed that EphA4 interacted with CDK5 and promoted its expression which in turn enhanced p-AKT expression and promoted cell adhesion-mediated drug resistance in multiple myeloma.
EphA4 was reduced in breast carcinoma, which is associated with high grade, advanced TNM stage, lymph node metastasis, and poor outcome of patients
Host EphA4 expression regulates cancer development mainly via EphA4-mediated IGF1 synthesis signal.
EPHA4 is overexpressed but not functionally active in Sezary syndrome.
The signaling complex appears to integrate the input from FGFR and EphA4, and release the output signal through FRS2alpha.
EphA4 induced accumulation of amyloid precursor protein through a Lyn-mediated pathway.
These findings suggest that increased EphA4-ephexin1 signaling in the PFC plays a role in the pathophysiology of depression.
Results suggest a circadian role for EphA4 in the SCN neuronal network, affecting the circadian system and contributing to the circadian response to light.
ephrin-B2 and EphA4 have graded and modular expression patterns in the developing inferior colliculus
findings suggest a role for EphA4 in shaping cortical oscillations during sleep that is independent from sleep need
The present study demonstrates that EphA4 and EphA7 receptors, despite their similar structure, have distinct in vivo effects on corticothalamic system projections into the ventrobasal complex /medial division of the posterior nuclear group.
These results suggest that EphA4, a novel and promising target for treatment, exacerbates EBI through an Ephexin-1/ROCK2 pathway after subarachnoid hemorrhage.
Our studies show that forward signaling through the EphA4 tyrosine kinase receptor, mediated by ephrins expressed by subpopulations of neuroblasts and astrocytes, is required for compact, directional organization of neuroblasts and astrocytes within the pathway and efficient transit of neuroblasts through the anterior forebrain to the olfactory bulb.
Findings suggest a putative novel mechanism for desipramine to modulate long-term potentiation through the regulation of the ephrinA3/EphA4 signaling pathway
Delineation of the specific mutation in EphA4 in this strain is important for further functional studies, such as protein-protein interactions, immunostaining and gene compensatory studies, investigating the mechanism underlying the effects of altered function of Eph family of receptor tyrosine kinases on phenotype.
the results of the present study demonstrated that angiogenesis occurs, and that the molecules EphA4 and ephrin-A5 are expressed in the hippocampal CA1 and CA3 areas throughout epileptogenesis. PECAM-1 may detect epileptic microvessel patterns in the hippocampi of mice and EphA4 may contribute to the microvessel plasticity via the ephrin-A5 signaling pathway.
results suggest that EphA4 is involved in circadian sleep regulation
The findings of this study revealed the behavioral and circuit-level impact of conditional EphA4 mutation in a transcriptionally defined spinal interneuron subpopulation.
Data show the effects of genetic loss of ephrin-A5, Eph receptors EphA4, and EphA7 on the development of medulloblastoma tumors in the smoothened (Smo) transgenic mouse model.
EphA4 mediates long-term contextual fear conditioning memory formation in a kinase-independent manner.
with an fibroblast growth factor signal, contributes to maintenance of radial glial cells self-renewal and repression of differentiation through neuronal lineage
Study show that EphA4 is a substrate for PTP-oc in osteoclasts and that the molecular mechanism contributing to the PTP-oc-induced up-regulation of the osteoclast activity in part involves its dephosphorylation and inactivation of the EphA4 signaling.
These findings suggest that the ternary complex of EphA, FGFR and FRS2alpha formed by ligand stimulation regulates self-renewal and differentiation of mouse embryonic neural stem/progenitor cells
expression of Eph A1, A2, A4, and A7 was strongly detected in endometrial epithelial cells during early pregnancy.
The EphA4 gene is significantly associated with litter size in pigs.
EphA4-dependent Brachyury expression is required for dorsal mesoderm involution in the Xenopus gastrula.
show that EphA4 and its putative ligand, ephrin-A1 are expressed in a complementary manner in the involuting mesodermal and non-involuting ectodermal layers of early gastrulae, respectively
In myelinating co-cultures and in zebrafish, we find that the number of mature oligodendrocytes does not change as result of manipulating signaling through the ephrinA1-EphA4 system. However, in both systems, inhibition of EphA4 signaling leads to a higher number of myelin sheaths formed by each oligodendrocyte. In isolated oligodendrocyte cultures, activation of EphA4 reduced process extension.
Downregulation of EphA4a compromises actomyosin cables and cells with different rhombomeric identity intermingle, and the phenotype is rescued enhancing myosin II activity.
EphA4 is required for cell adhesion and rhombomere-boundary formation in the zebrafish.
Data show that EfnB2a is required in developing hindbrain for normal cell affinity and that EphA4 and EfnB2a regulate cell affinity independently within their respective rhombomeres.
This gene belongs to the ephrin receptor subfamily of the protein-tyrosine kinase family. EPH and EPH-related receptors have been implicated in mediating developmental events, particularly in the nervous system. Receptors in the EPH subfamily typically have a single kinase domain and an extracellular region containing a Cys-rich domain and 2 fibronectin type III repeats. The ephrin receptors are divided into 2 groups based on the similarity of their extracellular domain sequences and their affinities for binding ephrin-A and ephrin-B ligands.
, EPH-like kinase 8
, TYRO1 protein tyrosine kinase
, ephrin type-A receptor 4
, receptor protein-tyrosine kinase HEK8
, tyrosine-protein kinase TYRO1
, tyrosine-protein kinase receptor SEK
, ephrin receptor epsilon
, EPH receptor A4
, ephrin receptor EphA4
, ephrin receptor EphA4-like
, ephrin type-A receptor 4-like
, tyrosine-protein kinase receptor MPK-3
, tyrosine-protein kinase receptor SEK-1
, ephrin type-A receptor 4-B
, receptor tyrosine kinase
, tyrosine-protein kinase receptor PAG
, eph receptor A3
, eph-like kinase 2
, eph-like receptor tyrosine kinase 1
, ephrin type-A receptor 4a
, tyrosine-protein kinase receptor ZEK2