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 molecule involved in the cytolytic function mediated by CTL and NK cells. In the present study, we have investigated various perimeters of DNAM-1-mediated signaling and adhesion. Although adhesion of DNAM-1 to its ligand does not require divalent cations, protein synthesis, or RNA transcription, activation of protein kinase C (PKC) is required for DNAM-1 functioning. Furthermore, mutation of the putative PKC-binding site in the cytoplasmic domain of DNAM-1 (Ser329 to Phe329) prevents both ligand binding and PMA-induced phosphorylation of the DNAM-1 receptor. These results indicate that PKC phosphorylates Ser329 of DNAM-1 and plays a critical role for both DNAM-1 adhesion and signaling.
Shibuya
A
A
Department of Immunobiology, DNAX Research Institute of Molecular and Cellular Biology, Palo Alto, CA 94304, USA.
Lanier
L L
LL
Phillips
J H
JH
D000595:Amino Acid Sequence; D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte; D002413:Cations, Divalent; D002448:Cell Adhesion / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D003593:Cytoplasm / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D004789:Enzyme Activation / Q000276:immunology; D006801:Humans; D007694:Killer Cells, Natural / Q000201:enzymology / Q000276:immunology; D051379:Mice; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D010766:Phosphorylation; D014176:Protein Biosynthesis; D011493:Protein Kinase C / Q000378:metabolism / Q000502:physiology*; D012313:RNA / Q000235:genetics; D011971:Receptors, Immunologic / Q000502:physiology*; D012694:Serine / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D015398:Signal Transduction / Q000276:immunology*; D013696:Temperature; D014158:Transcription, Genetic / Q000276:immunology; D014407:Tumor Cells, Cultured; D000098862:T Lineage-Specific Activation Antigen 1
D000945:Antigens, Differentiation, T-Lymphocyte; D000098862:T Lineage-Specific Activation Antigen 1; D002413:Cations, Divalent; D015815:Cell Adhesion Molecules; D011971:Receptors, Immunologic; D012694:Serine; D012313:RNA; D011493:Protein Kinase C