DNAX-activating protein 10 (DAP10)

DNAX-activating protein 10 (DAP10), also known as Hematopoietic cell signal transducer (HCST), is a transmembrane adapter protein primarily expressed in natural killer (NK) cells and certain subsets of T cells. It functions as the primary signaling subunit for the C-type lectin-like receptor NKG2D, which lacks its own signaling motif. Upon ligand binding to NKG2D, the YxxM motif in the cytoplasmic tail of DAP10 becomes phosphorylated, recruiting phosphatidylinositol 3-kinase (PI3K) and the adapter protein Grb2 to initiate downstream signaling cascades essential for immune cell activation and survival. [1][2] In the context of modern immunotherapy, DAP10 is a critical component in the design of next-generation Chimeric Antigen Receptors (CARs) for CAR-T and CAR-NK cell therapies. By incorporating the signaling domain of DAP10, researchers aim to mimic the co-stimulatory signals of innate immunity to enhance the persistence and tumor-killing efficacy of engineered cells against various cancers. [3][4] Beyond oncology, DAP10's role in modulating immune sensitivity makes it a subject of interest in research concerning autoimmune disorders and chronic viral infections where NK cell dysfunction is prevalent. [5] Sources: [1] UniProt (P83916 - HCST_HUMAN) [2] Wu, J., et al. (1999). 'An Activating Immunoreceptor Complex Formed by NKG2D and DAP10.' Science. [3] Chang, Y. H., et al. (2013). 'A chimeric receptor with NKG2D specificity enhances natural killer cell activation and killing of tumor cells.' Cancer Research. [4] PubMed (NCBI): 'DAP10 signaling in CAR-T/NK therapies'. [5] NIH Gene: 'HCST hematopoietic cell signal transducer'.

Other names

Hematopoietic cell signal transducerHCSTPIK3R4KAP10NKG2D-associated adapter protein

DAP10 acts as a signaling adapter for the NKG2D receptor; drugs targeting this pathway typically utilize the DAP10 cytoplasmic domain within Chimeric Antigen Receptors (CARs) to recruit PI3K and Grb2, thereby triggering cytotoxic effector functions and pro-survival signals in engineered immune cells.