Natural cytotoxicity triggering receptor 2 (NCR2) (NKp44)

Natural cytotoxicity triggering receptor 2 (NCR2), commonly known as NKp44, is a type I transmembrane glycoprotein and a member of the natural cytotoxicity receptor family (UniProt: O95944). It is specifically expressed on activated natural killer (NK) cells and certain subsets of innate lymphoid cells (ILCs), where it serves as a potent activating receptor (PubMed: 10359806). NKp44 recognizes a diverse array of ligands that are often upregulated on tumor cells or during viral infections, including BAG6/BAT3, MLL5, and PDGF-DD (PubMed: 21441498, PubMed: 25617461). Upon ligand binding, NKp44 typically signals through the DAP12 adapter protein to trigger NK cell degranulation and the secretion of pro-inflammatory cytokines like IFN-gamma. In oncology, NKp44 is being explored as a therapeutic target for bispecific NK cell engagers (NKCEs) and monoclonal antibodies designed to enhance the elimination of tumor cells (PubMed: 31160743). However, the receptor's function is complex, as certain isoforms contain an immunoreceptor tyrosine-based inhibitory motif (ITIM) that can deliver inhibitory signals, and some ligands like PCNA can also mediate inhibition (PubMed: 21357535). Therapeutic development must therefore account for the specific cellular context and ligand environment to ensure effective immune activation.

Other names

CD336LY95NK-p44Natural killer cell p44-related proteinNCR2

Agonistic activation of NK cell cytotoxicity and cytokine release (e.g., IFN-gamma) primarily through association with the ITAM-containing adapter protein DAP12 upon binding to stress-induced or viral ligands.