CD314/NKG2D

NKG2D (CD314), encoded by KLRK1, is an activating C-type lectin-like receptor that functions as a disulfide-linked homodimer on NK cells, CD8 T cells, gamma-delta T cells and NKT cells. Unlike most NK receptors it signals through the DAP10 adaptor, recruiting PI3K and Grb2 pathways, and in mice additionally through DAP12. Its ligands are stress-induced molecules, including MICA and MICB and the ULBP/RAET1 family members, which are upregulated upon viral infection, DNA damage and cellular transformation. As a principal sensor of cell stress, NKG2D drives NK cytotoxicity and is the basis of NKG2D-based chimeric antigen receptor designs.