NKp46, along with NKp30 and NKp44, are activating receptors that have been collectively termed the natural cytotoxicity receptors (NCR) . These receptors are expressed almost exclusively by NK cells and play a major role in triggering some of the key lytic activities of NK cells. Mouse NKp46, also known as MAR-1, is a type I transmembrane protein with two extracellular Ig-like domains. It has a positive charge in its transmembrane domain that permits association with the ITAM-bearing signal adapter proteins, CD3 zeta and Fc epsilon RI gamma. Studies with neutralizing antibodies indicate that the three NCR are primarily responsible for triggering the NK-mediated lysis of many human tumor cell lines. Blocking any of the NCRs individually resulted in partial inhibition of tumor cell lysis, but nearly complete inhibition of lysis was observed if all three receptors were blocked simultaneously. NKp46 has also been implicated in recognition of virus-infected cells through its capacity to bind to viral hemagglutinins.
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