Ephrin type-B receptor 3 is a protein encoded by a gene EPHB3 in humans. And its ligand ephrin receptor, ephrin, many processes of development of the nervous system in particular mediation,. Based on the sequence context and their structure, ephrins are divided into (EFNA) Class ephrin-A, which is fixed to the membrane by (EFNB) Class ephrin-B is a transmembrane protein and glycosylphosphatidylinositol linkage. Eph family of receptors are divided into two groups based on the similarity of their affinity for ephrin ligand binding and ephrin-AB extracellular domain sequence thereof. I comprises a subgroup of the maximum ephrin receptor tyrosine kinase (RTK) family. protein this gene encodes is a receptor of ephrin-B family members.
In vitro binding assays, our results confirm the two-hybrid assay: In this interaction, suggesting that it is not dependent on the catalytic activity of the receptor, PDZ domains AF6 is, EphB3K665R kinase-deficient EphB3 the wild-type I will bind both. Can not bind to PDZ domain separation Unlike the C-terminal mutant receptor EphB3V998A. However, the association of EphB3 in mammalian cells, it is strongly dependent on the catalytic activity of the receptor therefore became clear, the AF6 different lengths identified in binding behavior full coimmunoprecipitations are: wild-type receptor kinase dead AF6 length in these experiments that do not interact with, as opposed to a mutation EphB3K665R. Furthermore, NG108 cells and endogenous AF6 in 3T3 NIH can be shown to be phosphorylated specifically by EphB3 EPHB2 with a ligand-dependent manner. Interestingly, COS-1 cells, AF-6 were phosphorylated by C-terminal mutations EphB3V998A not associated with art PDZ. Thus, phosphorylation is independent of the AF6 PDZ domain-mediated interaction.
Using antiserum EphB3 to immunoprecipitated with anti-HA antibody COS-1 cells expressing EphB3 and transient HA-AF6 lysates to examine the interaction EphB3 AF6 between full length and in mammalian cells I was subjected to Western blot analysis. As show in FIG. AF6 can be demonstrated that it is associated with a EphB3 in mammalian cells and immunoprecipitated with the HA antibody from cells EphB3/HA-AF6-coexpressing is, EphB3 Figure 22B.
It is a substrate of the kinase activity of EphB3 AF6 and EPHB2. The cells with HA-AF6 combination of phosphorus AF6 EphB3 in mammalian cells, and mutations EphB3 or COS-1 wild type was co-transfected our, or if you want to determine. By Western blot analysis to phosphorylated tyrosine in contrast with the wild EphB3 cells co-expressing HA-AF6 and HA-AF6, HA-AF6 and co-expressing kinase dead EphB3K665R (Figure use of specific antibodies, of (in the figure, the cell Interestingly. 0.33). revealed tyrosine is phosphorylated, the, C-terminus mutations EphB3V998A not associated with PDZ domains AF6 test tube phosphorylates HA-AF6 in COS-1 cells I can.
Receptor tyrosine kinase that binds to the ligand ephrin-B through a plurality of the contact-dependent bidirectional device adjacent cells, so that families present in the cells adjacent to each other. Downstream between signaling pathways ligand ephrin reverse signaling is called downstream signaling the first signaling path of the receptor. Normally this is EPHB2 redundancy and overlap there. Development regulations such as anterior commissure and the corpus callosum, as EPHB2, neuron axon guidance function when connecting major hemisphere between the two between the temporal lobe of the cerebral cortex. In addition to its role in axon guidance, and plays an important role redundant with ephrin-B receptor other formation and maturation development of excitatory synapses and dendritic spines. To control other aspects of development through the regulation of cell migration and positioning. This development of palate epithelium example angiogenesis, and thymus development are included. Reverse signal to EFNB2/EPHB3 through complex forward and also to regulate the adhesion of block sewer tubularize and cell migration and urethra. Finally, I have played an important role in stem cells isolated single differentiation of intestinal epithelial differentiation in the script.
Four hetero ligand binding. I consists of ephrin receptor dimer and tetramer hetero. Oligomerization, it is necessary to induce a biological response probably. Subcellular localization: cell membrane, is a single-pass type I membrane protein. Projection cell dendrites.
Eph receptors is involved in the regulation of cancer malignancy. Here, tyrosine is reduced, as described above, ephrin-B2 or ephrin-B1, downregulated substantially Despite overexpression of EphB3 in human non-small cell lung cancer, or expression of the cognate ligand to understand I phosphorylates the EphB3 is. Insertion force of EphB3 kinase in non-small cell expressing EphB3 cell lung cancer cells, inhibits the in vivo metastatic dissemination in cell migration and whether in vitro. Furthermore, the response to the activation of EphB3-mediated assembly oxide and Akt leads to reduced phosphorylation of Akt, New EphB3 binding protein, receptor C-kinase-1 is activated ternary complex signal comprising a protein phosphatase 2A subsequent inhibition of cell migration to identify. In our study, the potential treatment by and, to clarify the EphB3 of non-small cell lung cancer, which is kinase activation associated with tumor suppressor signaling pathways novel and activate EphB3 signaling to inhibit tumor metastasis I offer strategy.