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Molecular and Cellular Biology, December 2002, p. 8787-8795, Vol. 22, No. 24
0270-7306/02/$04.00+0     DOI: 10.1128/MCB.22.24.8787-8795.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

The Drosophila Atypical Protein Kinase C-Ref(2)P Complex Constitutes a Conserved Module for Signaling in the Toll Pathway

Antonia Avila,1 Neal Silverman,2 María T. Diaz-Meco,1 and Jorge Moscat1*

Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas, Universidad Autónoma, Canto Blanco, 28049 Madrid, Spain,1 Department of Medicine, Division of Infectious Disease and Immunology, University of Massachusetts Medical School, Worcester, Massachusetts 016552

Received 12 April 2002/ Returned for modification 17 June 2002/ Accepted 11 September 2002

Recent results showed the critical role of the mammalian p62-atypical protein kinase C (aPKC) complex in the activation of NF-{kappa}B 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-{kappa}B homologues Dif and Dorsal. However, DaPKC does not appear to be important for the other Drosophila NF-{kappa}B signaling cascade, which activates the NF-{kappa}B 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.

* Corresponding author. Mailing address: CBMSO, Universidad Autónoma, Canto Blanco, 28049 Madrid, Spain. Phone: 34-913978039. Fax: 34-917616184. E-mail: jmoscat{at}cbm.uam.es.

Molecular and Cellular Biology, December 2002, p. 8787-8795, Vol. 22, No. 24
0022-538X/02/$04.00+0     DOI: 10.1128/MCB.22.24.8787-8795.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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