EphB6, also known as Hep and Mep, is a 110 kDa member of the Eph receptor tyrosine kinase family. The A and B classes of Eph proteins are distinguished by ligand preference and have a common structural organization. The human EphB6 cDNA encodes a 1006 amino acid (aa) precursor that includes a 16 aa signal sequence, a 563 aa extracellular domain (ECD), a 21 aa transmembrane segment, and a 406 aa cytoplasmic domain. EphB6 is primarily expressed in brain, pancreas, thymus, and peripheral T cells. EphB6 forms stable heterodimers with EphB1 and participates in signal transduction by association with other enzymatically active molecules. Binds to ephrin-B1 and ephrin-B2. Modulates cell adhesion and migration by exerting both positive and negative effects upon stimulation with ephrin-B2. Inhibits JNK activation, T-cell receptor-induced IL-2 secretion and CD25 expression upon stimulation with ephrin-B2. The level of EphB6 expression is inversely correlated with tumor aggressiveness in a variety of malignancies. EphB6 also functions as a T cell co-stimulatory molecule. EphB6 clusters with the T cell receptor and participates in the subsequent attenuation of the T cell response.
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