Natural cytotoxicity-triggering receptor 2 (NKp44)

Natural cytotoxicity-triggering receptor 2, commonly known as NKp44, is a 44-kDa type I transmembrane glycoprotein and a key member of the natural cytotoxicity receptor family. Encoded by the NCR2 gene, it is uniquely expressed on activated natural killer (NK) cells but is absent on resting NK cells or T cells, making it a specific marker for NK cell activation. It typically functions as an activating receptor that, upon binding to various tumor or viral ligands (such as hemagglutinin), signals through the DAP12 adapter protein to trigger cytotoxicity and the release of pro-inflammatory cytokines like IFN-gamma and TNF-alpha. However, NKp44 can also mediate inhibitory signals when its NKp44-1 isoform interacts with ligands like PCNA on tumor cells, a mechanism exploited by cancers to evade immune detection. Therapeutic interest in NKp44 focuses on activating its signaling to boost anti-tumor immunity or developing peptides and CAR-based therapies that target its ligands or block inhibitory receptor interactions.

Other names

NKp44NCR2CD336NK-p44NKP44LY95dJ149M18.1Lymphocyte antigen 95 homologNK cell-activating receptorNatural killer cell p44-related protein

Activation of NK cell-mediated cytotoxicity and cytokine production via DAP12-dependent signaling upon ligand binding; inhibition of tumor immune evasion by blocking inhibitory receptor-ligand interactions (e.g., NKp44-1 and PCNA); redirection of immune cells using CAR-T/NK technology targeting NKp44 ligands.