Fig. 1

Created with BioRender.com. The bidirectional arrow represents the interaction between DNAM-1 and its ligands. DNAM-1 exerts a costimulatory effect after engagement with its ligands CD155 and CD112. The intrinsic cell signaling cascade of DNAM-1 subsequently occurs in NK cells, and the sites of DNAM-1 S³²⁹ and Y³²² are phosphorylated under the synergistic action of PKC and Fyn src kinase induced by LFA-1, resulting in dual SLP-76 phosphorylation at Y¹²⁸ and Y¹¹³. This phosphorylated form of SLP-76 binds to Vav1 molecules to activate PLC-γ2. Additionally, phosphorylated DNAM-1 recruits the adaptor Grb2, which leads to the activation of Vav-1, PI3K, and phospholipase C-γ1 (PLC-γ1). Both pathways lead to NK cell cytotoxicity changes