| RRC ID |
21931
|
| 著者 |
Kleino A, Myllymäki H, Kallio J, Vanha-aho LM, Oksanen K, Ulvila J, Hultmark D, Valanne S, Rämet M.
|
| タイトル |
Pirk is a negative regulator of the Drosophila Imd pathway.
|
| ジャーナル |
J Immunol
|
| 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.
|
| 巻・号 |
180(8)
|
| ページ |
5413-22
|
| 公開日 |
2008-4-15
|
| DOI |
10.4049/jimmunol.180.8.5413
|
| PII |
180/8/5413
|
| PMID |
18390723
|
| MeSH |
Amino Acid Sequence
Animals
Carrier Proteins / chemistry
Carrier Proteins / genetics
Carrier Proteins / immunology
Carrier Proteins / metabolism*
Drosophila Proteins / chemistry
Drosophila Proteins / genetics
Drosophila Proteins / immunology
Drosophila Proteins / metabolism*
Drosophila melanogaster / immunology*
Drosophila melanogaster / metabolism
Drosophila melanogaster / microbiology*
Enterobacter cloacae / immunology*
Enterobacter cloacae / physiology
Genes, Insect
Molecular Sequence Data
NF-kappa B / immunology
NF-kappa B / metabolism
Oligonucleotide Array Sequence Analysis
RNA Interference
Sequence Alignment
Signal Transduction
|
| IF |
4.886
|
| 引用数 |
119
|
|
WOS 分野
|
IMMUNOLOGY
|
| リソース情報 |
| ショウジョウバエ |
15678R-1
15678R-2 |
