The Drosophila atypical protein kinase C-ref(2)p complex constitutes a conserved module for signaling in the toll pathway
Department of Medicine, Division of Infectious Diseases and Immunology
Active Transport, Cell Nucleus; Amino Acid Sequence; Animals; Cell Fractionation; Cell Line; DNA-Binding Proteins; Drosophila Proteins; Drosophila melanogaster; Genes, Reporter; Insect Proteins; Lipopolysaccharides; Molecular Sequence Data; NF-kappa B; Nuclear Proteins; Phosphoproteins; Promoter Regions (Genetics); Protein Kinase C; Proteins; RNA Interference; Receptors, Cell Surface; Recombinant Fusion Proteins; Signal Transduction; TNF Receptor-Associated Factor 2; Toll-Like Receptors; Transcription Factors; Transcription, Genetic
Recent results showed the critical role of the mammalian p62-atypical protein kinase C (aPKC) complex in the activation of NF-kappaB in response to different stimuli. Here we demonstrate using the RNA interference technique on Schneider cells that the Drosophila aPKC (DaPKC) is required for the stimulation of the Toll-signaling pathway, which activates the NF-kappaB homologues Dif and Dorsal. However, DaPKC does not appear to be important for the other Drosophila NF-kappaB signaling cascade, which activates the NF-kappaB homologue Relish in response to lipopolysaccharides. Interestingly, DaPKC functions downstream of the nuclear translocation of Dorsal or Dif, controlling the transcriptional activity of the Drosomycin promoter. We also show that the Drosophila Ref(2)P protein is the homologue of mammalian p62 as it binds to DaPKC, its overexpression is sufficient to activate the Drosomycin but not the Attacin promoter, and its depletion severely impairs Toll signaling. Collectively, these results demonstrate the conservation of the p62-aPKC complex for the control of innate immunity signal transduction in Drosophila melanogaster.
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Citation: Mol Cell Biol. 2002 Dec;22(24):8787-95.
Avila, Antonia; Silverman, Neal S.; Diaz-Meco, Maria T.; and Moscat, Jorge, "The Drosophila atypical protein kinase C-ref(2)p complex constitutes a conserved module for signaling in the toll pathway" (2002). Infectious Diseases and Immunology Publications and Presentations. Paper 14.