DNAM-1/CD226 is a member of the immunoglobulin-like superfamily. It is expressed on T cells, natural killer (NK) cells, monocytes, and macrophages. It is a major activating receptor on NK cells. Engagement with its ligands Nectin-2 (CD112) and PVR (poliovirus receptor, also known as CD155) on the target cells leads to downstream activation of ERK, AKT, and PLCg2 signaling pathways that are crucial for NK activation and NK-mediated killing. LFA-1 physically associates with DNAM-1/CD226 and contributes to its signaling. Activating signal of DNAM-1/CD226 is counterbalanced by inhibitory receptors TIGIT and CD96, competing for the common ligands CD122 and PVR.
