Phospho-EPHB1/2/3/4 (Tyr600/Tyr602/Tyr614/Tyr596) Antibody - #AF8145

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. Functions in axon guidance during development. Involved in the guidance of commissural axons, that form a major interhemispheric connection between the 2 temporal lobes of the cerebral cortex. Also involved in guidance of contralateral inner ear efferent growth cones at the midline and of retinal ganglion cell axons to the optic disk. In addition to axon guidance, also regulates dendritic spines development and maturation and stimulates the formation of excitatory synapses. Upon activation by EFNB1, abolishes the ARHGEF15-mediated negative regulation on excitatory synapse formation. Controls other aspects of development including angiogenesis, palate development and in inner ear development through regulation of endolymph production. Forward and reverse signaling through the EFNB2/EPHB2 complex regulate movement and adhesion of cells that tubularize the urethra and septate the cloaca. May function as a tumor suppressor. May be involved in the regulation of platelet activation and blood coagulation.

Autophosphorylated; ligand binding stimulates autophosphorylation on tyrosine residues.

Polyubiquitinated; ligand binding stimulates ubiquitination.

Ligand binding induces cleavage by matrix metalloproteinases (MMPs) such as MMP7/MMP9, producing an EphB2/N-terminal fragment (NTF) and a C-terminal long fragment (EphB2-LF). EphB2-LF is further cleaved by MMPs, producing EphB2/CTF1 which is further cleaved by the PS1/gamma-secretase producing EphB2/CTF2.

Cell membrane>Single-pass type I membrane protein. Cell projection>Axon. Cell projection>Dendrite.

Brain, heart, lung, kidney, placenta, pancreas, liver and skeletal muscle. Preferentially expressed in fetal brain.

Heterotetramer upon binding of the ligand (By similarity). The heterotetramer is composed of an ephrin dimer and a receptor dimer. Interacts (via PDZ-binding motif) with GRIP1 and PICK1 (via PDZ domain) (By similarity). Interacts with ARHGEF15; mediates ARHGEF15 phosphorylation, ubiquitination and degradation by the proteasome (By similarity). Interacts with AQP1; involved in endolymph production in the inner ear (By similarity). Interacts with SPSB1 and SPSB4. The phosphorylated form interacts with RASA1 (via SH2 domain 1) (By similarity). Interacts with EFNA5 (By similarity).

Belongs to the protein kinase superfamily. Tyr protein kinase family. Ephrin receptor subfamily.

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. Generally has an overlapping and redundant function with EPHB2. Like EPHB2, functions in axon guidance during development regulating for instance the neurons forming the corpus callosum and the anterior commissure, 2 major interhemispheric connections between the temporal lobes of the cerebral cortex. In addition to its role in axon guidance plays also an important redundant role with other ephrin-B receptors in development and maturation of dendritic spines and the formation of excitatory synapses. Controls other aspects of development through regulation of cell migration and positioning. This includes angiogenesis, palate development and thymic epithelium development for instance. Forward and reverse signaling through the EFNB2/EPHB3 complex also regulate migration and adhesion of cells that tubularize the urethra and septate the cloaca. Finally, plays an important role in intestinal epithelium differentiation segregating progenitor from differentiated cells in the crypt.

Phosphorylated. Autophosphorylates upon ligand-binding. Autophosphorylation on Tyr-614 is required for interaction with SH2 domain-containing proteins.

Cell membrane>Single-pass type I membrane protein. Cell projection>Dendrite.

Ubiquitous.

Heterotetramer upon binding of the ligand. The heterotetramer is composed of an ephrin dimer and a receptor dimer. Oligomerization is probably required to induce biological responses (By similarity).

Belongs to the protein kinase superfamily. Tyr protein kinase family. Ephrin receptor subfamily.

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.

Phosphorylated; autophosphorylation is stimulated by EFNB2.

Cell membrane>Single-pass type I membrane protein.

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, melanocyte and cervix.

Heterotetramer upon binding of the ligand. The heterotetramer is composed of an ephrin dimer and a receptor dimer. Oligomerization is probably required to induce biological responses (By similarity). Interacts with RASA1; the interaction depends on EPHB4 tyrosine-phosphorylation.

Belongs to the protein kinase superfamily. Tyr protein kinase family. Ephrin receptor subfamily.