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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. 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. EphrinA R3 mutations are primarily identified in lung, colorectal, and hepatocellular cancers, melanoma, and glioblastoma. EphA R3 protein is localized within the cytoplasm and at the cell membrane and its expression is correlated with tumor size, tumor grade and metastasis EphrinA R3 activity has ephrin- and kinase-dependent tumor suppressing activities, which are disrupted by somatic cancer mutations. Selected intracellular EphA3 tumor-associated point mutations decrease receptor expression level and/or receptor tyrosine kinase (RTK) activity. EphA R3 is overexpressed in many hematologic malignancies thus making it an important target for therapeutic intervention of malignancies. The gene for EphA R3 is present on chromosome 3p11.2.
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