Natural cytotoxicity triggering receptor 2 (NKp44) (NKp44)

Natural cytotoxicity triggering receptor 2, commonly known as NKp44, is a type I transmembrane glycoprotein and a prominent member of the natural cytotoxicity receptor (NCR) family. Distinct from NKp46 and NKp30, NKp44 is not constitutively expressed on resting natural killer (NK) cells but is rapidly induced upon activation by cytokines such as IL-2. It plays a pivotal role in the innate immune response by recognizing various ligands, including tumor-associated molecules like BAG6 and PDGF-DD, as well as viral proteins such as influenza hemagglutinin (UniProt ID: O95944; PubMed: 10358178). Upon engagement, NKp44 signals through its association with the DNAX-activation protein 12 (DAP12), initiating a signaling cascade that results in the directed lysis of malignant or infected cells. In the context of oncology, NKp44 is a high-priority target for next-generation immunotherapies, including CAR-NK cell therapies and bispecific antibodies, aimed at enhancing the tumor-killing capacity of the innate immune system (PubMed: 31034451). However, some tumors exploit this pathway by shedding soluble ligands that act as decoys, highlighting the target's importance in both immune activation and tumor-mediated immune evasion.

Other names

NCR2CD336NK-p44LY95Natural killer cell p44-related protein

Activation of natural killer (NK) cells through ligand binding to the NKp44 receptor, triggering intracellular signaling via the ITAM-containing adapter protein DAP12, which leads to the release of cytotoxic granules (perforin/granzymes) and pro-inflammatory cytokines like IFN-gamma.