title: The Drosophila atypical protein kinase C-ref(2)p complex constitutes a conserved module for signaling in the toll pathway.
abstract: 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.
authors.affiliation: Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas, Universidad Autónoma, Canto Blanco, 28049 Madrid, Spain.
authors.forename: Antonia
authors.initials: A
authors.lastname: Avila
authors.forename: Neal
authors.initials: N
authors.lastname: Silverman
authors.forename: María T
authors.initials: MT
authors.lastname: Diaz-Meco
authors.forename: Jorge
authors.initials: J
authors.lastname: Moscat
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000502:physiology; D000595:Amino Acid Sequence; D000818:Animals; D002458:Cell Fractionation; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D017930:Genes, Reporter; D019476:Insect Proteins / Q000235:genetics / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000378:metabolism; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011493:Protein Kinase C / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism; D034622:RNA Interference; D011956:Receptors, Cell Surface / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D047992:TNF Receptor-Associated Factor 2; D051193:Toll-Like Receptors; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D004268:DNA-Binding Proteins; C084428:Dif protein, Drosophila; D029721:Drosophila Proteins; D019476:Insect Proteins; D008070:Lipopolysaccharides; D016328:NF-kappa B; D009687:Nuclear Proteins; D010750:Phosphoproteins; D011506:Proteins; D011956:Receptors, Cell Surface; D011993:Recombinant Fusion Proteins; C101626:Rel protein, Drosophila; D047992:TNF Receptor-Associated Factor 2; C068721:Tl protein, Drosophila; D051193:Toll-Like Receptors; D014157:Transcription Factors; C062236:dl protein, Drosophila; C080596:ref(2)P protein, Drosophila; C077938:cact protein, Drosophila; C091227:DRS protein, Drosophila; C115015:PKC-3 protein; D011493:Protein Kinase C