Ephrin-A1 is a member of the A-type ephrin family of cell surface proteins that function as ligands for the A-type Eph receptor tyrosine kinase family. Ephrin-A1 can be induced by TNF and IL1B. Its expression levels can be down-regulated in primary glioma tissues compared to the normal tissues. The soluble monomeric form is expressed in the glioblastoma multiforme (GBM) and breast cancer cells. Soluble Ephrin-A1 is necessary for the transformation of HeLa and SK-BR3 cells and participates in the relocalization of EPHA2 away from sites of cell-cell contact during transformation. Ephrin-A1 plays an important role in angiogenesis and tumor neovascularization.
Ephrins-A3 belongs the Ephrins ligand family which involved in a variety of biological processes, especially in the nervous system and in erythropoiesis. It is shown that Ephrin-A3 is expressed in brain, skeletal muscle, spleen, thymus, prostate, testis, ovary, small intestine, and peripheral blood leukocytes. Ephrin-A3 has a GPI anchor following the extracellular sequence and a signal sequence of 22 amino acids. Ephrin-A3 can bind EphA2, EphA3, EphA4, EphA5, EphA6, EphA7, EphA8 and EphB1. Futhermore, it is associated with tumor growth and metastasis.
Ephrin-A4 is a member of the ephrin ligand family which binds members of the Eph receptor family. All ligands share a conserved extracellular sequence; which most likely corresponds to the receptor binding domain. Ephrin-A4 consists of approximately 125 amino acids and includes four invariant cysteines; It has been shown to bind EphA2; EphA3; EphA4; EphA5; EphA6; EphA7; and EphB1. Ephrin-A4 binds promiscuously Eph receptors residing on adjacent cells; leading to contact-dependent bidirectional signaling into neighboring cells. It may play a role in the interaction between activated B-lymphocytes and dendritic cells in tonsils.
Ephrin-A5 (EFNA5) belongs to the ephrin family,contains 1 ephrin RBD (ephrin receptor-binding) domain. Ephrin-A5 is a cell surface GPI-bound ligand for Eph receptors, a family of receptor tyrosine kinases which are crucial for migration, repulsion and adhesion during neuronal, vascular and epithelial development. It binds promiscuously Eph receptors residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The interaction of EFNA5 with EPHA5 also mediates communication between pancreatic islet cells to regulate glucose-stimulated insulin secretion. Cognate/functional ligand for EPHA7, their interaction regulates brain development modulating cell-cell adhesion and repulsion.
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