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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
11
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pubmed:dateCreated |
2010-5-20
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pubmed:abstractText |
Because NF-kappaB signaling pathways are highly conserved in evolution, the fruit fly Drosophila melanogaster provides a good model to study these cascades. We carried out an RNA interference (RNAi)-based genome-wide in vitro reporter assay screen in Drosophila for components of NF-kappaB pathways. We analyzed 16,025 dsRNA-treatments and identified 10 novel NF-kappaB regulators. Of these, nine dsRNA-treatments affect primarily the Toll pathway. G protein-coupled receptor kinase (Gprk)2, CG15737/Toll pathway activation mediating protein, and u-shaped were required for normal Drosomycin response in vivo. Interaction studies revealed that Gprk2 interacts with the Drosophila IkappaB homolog Cactus, but is not required in Cactus degradation, indicating a novel mechanism for NF-kappaB regulation. Morpholino silencing of the zebrafish ortholog of Gprk2 in fish embryos caused impaired cytokine expression after Escherichia coli infection, indicating a conserved role in NF-kappaB signaling. Moreover, small interfering RNA silencing of the human ortholog GRK5 in HeLa cells impaired NF-kappaB reporter activity. Gprk2 RNAi flies are susceptible to infection with Enterococcus faecalis and Gprk2 RNAi rescues Toll(10b)-induced blood cell activation in Drosophila larvae in vivo. We conclude that Gprk2/GRK5 has an evolutionarily conserved role in regulating NF-kappaB signaling.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
1550-6606
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pubmed:author |
pubmed-author:AiraksinenLauraL,
pubmed-author:EngströmYlvaY,
pubmed-author:EsfahaniShiva SeyedoleslamiSS,
pubmed-author:HultmarkDanD,
pubmed-author:KallioJenniJ,
pubmed-author:KaustioMeriM,
pubmed-author:KleinoAnniA,
pubmed-author:KotipeltoTapioT,
pubmed-author:MurumägiAstridA,
pubmed-author:MyllymäkiHennaH,
pubmed-author:ParikkaMataleenaM,
pubmed-author:RämetMikaM,
pubmed-author:SchmidMartin RudolfMR,
pubmed-author:SilvennoinenOlliO,
pubmed-author:UlvilaJohannaJ,
pubmed-author:ValanneSusannaS
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pubmed:issnType |
Electronic
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pubmed:day |
1
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pubmed:volume |
184
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
6188-98
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pubmed:meshHeading |
pubmed-meshheading:20421637-Animals,
pubmed-meshheading:20421637-Blotting, Western,
pubmed-meshheading:20421637-Drosophila,
pubmed-meshheading:20421637-Drosophila Proteins,
pubmed-meshheading:20421637-G-Protein-Coupled Receptor Kinase 2,
pubmed-meshheading:20421637-G-Protein-Coupled Receptor Kinase 5,
pubmed-meshheading:20421637-Gram-Negative Chemolithotrophic Bacteria,
pubmed-meshheading:20421637-Humans,
pubmed-meshheading:20421637-Immunity, Innate,
pubmed-meshheading:20421637-Immunohistochemistry,
pubmed-meshheading:20421637-Immunoprecipitation,
pubmed-meshheading:20421637-NF-kappa B,
pubmed-meshheading:20421637-RNA Interference,
pubmed-meshheading:20421637-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:20421637-Signal Transduction,
pubmed-meshheading:20421637-Zebrafish
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pubmed:year |
2010
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pubmed:articleTitle |
Genome-wide RNA interference in Drosophila cells identifies G protein-coupled receptor kinase 2 as a conserved regulator of NF-kappaB signaling.
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pubmed:affiliation |
Institute of Medical Technology, University of Tampere, Tampere, Finland.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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