Open Close
Reference
Citation
Kleino, A., Myllymaki, H., Kallio, J., Vanha-aho, L.M., Oksanen, K., Ulvila, J., Hultmark, D., Valanne, S., Ramet, M. (2008). Pirk is a negative regulator of the Drosophila Imd pathway.  J. Immunol. 180(8): 5413--5422.
FlyBase ID
FBrf0206659
Publication Type
Research paper
Abstract

NF-kappaB transcription factors are involved in evolutionarily conserved signaling pathways controlling multiple cellular processes including apoptosis and immune and inflammatory responses. Immune response of the fruit fly Drosophila melanogaster to Gram-negative bacteria is primarily mediated via the Imd (immune deficiency) pathway, which closely resembles the mammalian TNFR signaling pathway. Instead of cytokines, the main outcome of Imd signaling is the production of antimicrobial peptides. The pathway activity is delicately regulated. Although many of the Imd pathway components are known, the mechanisms of negative regulation are more elusive. In this study we report that a previously uncharacterized gene, pirk, is highly induced upon Gram-negative bacterial infection in Drosophila in vitro and in vivo. pirk encodes a cytoplasmic protein that coimmunoprecipitates with Imd and the cytoplasmic tail of peptidoglycan recognition protein LC (PGRP-LC). RNA interference-mediated down-regulation of Pirk caused Imd pathway hyperactivation upon infection with Gram-negative bacteria, while overexpression of pirk reduced the Imd pathway response both in vitro and in vivo. Furthermore, pirk-overexpressing flies were more susceptible to Gram-negative bacterial infection than wild-type flies. We conclude that Pirk is a negative regulator of the Imd pathway.

PubMed ID
PubMed Central ID
DOI
Associated Information
Comments
Associated Files
Other Information
Secondary IDs
    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    J. Immunol.
    Title
    Journal of Immunology
    Publication Year
    1950-
    ISBN/ISSN
    0022-1767
    Data From Reference
    Alleles (5)
    Gene Groups (1)
    Genes (34)
    Physical Interactions (2)
    Cell Lines (1)
    Natural transposons (1)
    Insertions (5)
    Experimental Tools (2)
    Transgenic Constructs (2)