Rec Tyr Kinase (Eph B1 Cy.) (ELK) Antibody – Sheep Polyclonal

Ephrin receptors and their ligands, the ephrins, mediate numerous developmental processes, particularly in the nervous system. Based on their structures and sequence relationships, ephrins are divided into the ephrin-A (EFNA) class, which are anchored to the membrane by a glycosylphosphatidylinositol linkage, and the ephrin-B (EFNB) class, which are transmembrane proteins. The Eph family of 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. Ephrin receptors make up the largest subgroup of the receptor tyrosine kinase (RTK) family. The protein encoded by this gene is a receptor for ephrin-B family members. [provided by RefSeq, Jul 2008]

Function: 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. Cognate/functional ephrin ligands for this receptor include EFNB1, EFNB2 and EFNB3. During nervous system development, regulates retinal axon guidance redirecting ipsilaterally ventrotemporal retinal ganglion cells axons at the optic chiasm midline. This probably requires repulsive interaction with EFNB2. In the adult nervous system together with EFNB3, regulates chemotaxis, proliferation and polarity of the hippocampus neural progenitors. Beside its role in axon guidance plays also an important redundant role with other ephrin-B receptors in development and maturation of dendritic spines and synapse formation. May also regulate angiogenesis. More generally, may play a role in targeted cell migration and adhesion. Upon activation by EFNB1 and probably other ephrin-B ligands activates the MAPK/ERK and the JNK signaling cascades to regulate cell migration and adhesion respectively. Ref.2 Ref.9 Ref.11 Ref.12 Ref.13

Catalytic activity: ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.

Subunit structure: 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 EPHB6; transphosphorylates EPHB6 to form an active signaling complex. Interacts with PICK1

By similarity. Interacts (through Tyr-594) with NCK1 (via SH2 domain); activates the JUN cascade to regulate cell adhesion

By similarity. The ligand-activated form interacts (through Tyr-928) with GRB7 and GRB10 (via SH2 domains). The ligand-activated form interacts (residues within the catalytic domain) with GRB2 (via SH2 domain). Interacts with GRB2, SHC1 and SRC; activates the MAPK/ERK cascade to regulate cell migration. Interacts with CBL; regulates receptor degradation through ubiquitination. Interacts with ACP1. Ref.2 Ref.7 Ref.9 Ref.10 Ref.11 Ref.12 Ref.13

Subcellular location: Cell membrane; Single-pass type I membrane protein. Early endosome membrane. Cell projection › dendrite

By similarity Ref.13.

Tissue specificity: Preferentially expressed in brain.

Post-translational modification: Phosphorylated. Autophosphorylation is stimulated by the ligand EFNB1. Required for interaction with SH2 domain-containing interactors, for activation of the MAPK/ERK and JUN signaling cascades and for ubiquitination by CBL. Ref.7 Ref.11 Ref.13Ubiquitinated; (EFNB1)ligand-induced poly- and/or multi-ubiquitination by CBL is regulated by SRC and leads to lysosomal degradation. Ref.13

Sequence similarities: Belongs to the protein kinase superfamily. Tyr protein kinase family. Ephrin receptor subfamily.Contains 1 Eph LBD (Eph ligand-binding) domain.Contains 2 fibronectin type-III domains.Contains 1 protein kinase domain.Contains 1 SAM (sterile alpha motif) domain.

Sequence caution: The sequence AAB94627.1 differs from that shown. Reason: wrong intron-exon boundaries.The sequence AAB94628.1 differs from that shown. Reason: wrong intron-exon boundaries.The sequence AAD02031.1 differs from that shown. Reason: Chimeric cDNA.