PROTEIN-KINASE-C IS INVOLVED IN THE REGULATION OF BOTH SIGNALING AND ADHESION MEDIATED BY DNAX ACCESSORY MOLECULE-1 RECEPTOR

DNAX accessory molecule-1 (DNAM-1) is a signal-transducing adhesion mo lecule involved in the cytolytic function mediated by CTL and NK cells , In the present study, we have investigated various perimeters of DNA M-1-mediated signaling and adhesion. Although adhesion of DNAM-1 to it s ligand does not require divalent cations, protein synthesis, or RNA transcription, activation of protein kinase C (PKC) is required for DN AM-1 functioning. Furthermore, mutation of the putative PKC-binding si te in the cytoplasmic domain of DNAM-1 (Ser(329) to Phe(329)) prevents both ligand binding and PMA-induced phosphorylation of the DNAM-1 rec eptor. These results indicate that PKC phosphorylates Ser(329) of DNAM -1 and plays a critical role for both DNAM-1 adhesion and signaling.