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Background
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The Ephrin receptors represent the largest group of Receptor Tyrosine Kinases, comprising of 14 members and divided in two subclasses (class A & B ephrin ligands) based on their abilities to bind and activate each other, and on sequence conservation. Ephrin-A (EFNA) class is anchored to the membrane by a glycosylphosphatidylinositol linkage, and the ephrin-B (EFNB) classes are trans-membrane proteins. The Eph family of receptors are similarly divided into 2 groups based on the similarity of their extracellular domain sequences and their affinities for binding ephrin-A and ephrin-B ligands. Ephrins interact with a variety of membrane receptors that respond to chemokines, neurotransmitters or growth factors. Eph receptors are involved in central nervous system function and development, and in the modulation of different types of nociception. Eph receptors and their ligands play important roles in the regulation of cancer cell migration and invasion and are key regulators of axon guidance. They function in a variety of signaling modes by transducing signals from the cell exterior to the interior through ligand-induced activation of their kinase domain. Ephrin A7, a member of the ephrin family, encodes a soluble splice variant that acts as an extrinsic tumor suppressor. The common deletion of chromosome 6q has identified the ephrin receptor A7 (EPHA7) as a tumor suppressor in lymphomas. EPHA7 is implicated in lung cancer and other tumors, because of a broader therapeutic potential for antibody-mediated delivery of this tumor suppressor for cancer therapy. EPHA7 interferes with another Eph-receptor and blocks oncogenic signals in lymphoma cells. Consistent with this drug-like activity, administration of the purified EPHA7 protein produces antitumor effects against xenografted human lymphomas. Fusing EPHA7 to the anti-CD20 antibody (rituximab) can directly target this tumor suppressor to lymphomas in vivo thus rendering EPHA7 as tumor suppressor with immediate therapeutic potential. EPH and EPH-related receptors are 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 gene for EphAR6 is present on chromosome 3q11.2.
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