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  • Valanne, SusannaUniversity of Tampere,Hultmark (author)

Genome-Wide RNA Interference in Drosophila Cells Identifies G Protein-Coupled Receptor Kinase 2 as a Conserved Regulator of NF-kappa B Signaling

  • Article/chapterEnglish2010

Publisher, publication year, extent ...

  • 2010-06-01
  • The American Association of Immunologists,2010
  • printrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:su-49704
  • https://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-49704URI
  • https://doi.org/10.4049/jimmunol.1000261DOI
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-286594URI
  • https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-38693URI

Supplementary language notes

  • Language:English
  • Summary in:English

Part of subdatabase

Classification

  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • authorCount :16
  • Because NF-kappa B 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-kappa B pathways. We analyzed 16,025 dsRNA-treatments and identified 10 novel NF-kappa B 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 I kappa B homolog Cactus, but is not required in Cactus degradation, indicating a novel mechanism for NF-kappa B 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-kappa B signaling. Moreover, small interfering RNA silencing of the human ortholog GRK5 in HeLa cells impaired NF-kappa B 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-kappa B signaling. The Journal of Immunology, 2010, 184: 6188-6198.

Subject headings and genre

Added entries (persons, corporate bodies, meetings, titles ...)

  • Myllymäki, Henna (author)
  • Kallio, Jenni (author)
  • Schmid, Martin Rudolf,1979-Umeå universitet,Institutionen för molekylärbiologi (Medicinska fakulteten),Hultmark(Swepub:umu)masc0012 (author)
  • Kleino, AnniUniversity of Tampere,Hultmark (author)
  • Murumägi, Astrid (author)
  • Airaksinen, Laura (author)
  • Kotipelto, Tapio (author)
  • Kaustio, Meri (author)
  • Ulvila, Johanna (author)
  • Seyedoleslami Esfahani, ShivaStockholms universitet,Institutionen för molekylärbiologi och funktionsgenomik(Swepub:su)sseye (author)
  • Engström, YlvaStockholms universitet,Institutionen för molekylärbiologi och funktionsgenomik(Swepub:su)yleng (author)
  • Silvennoinen, Olli (author)
  • Hultmark, Dan,1949-Umeå universitet,Institutionen för molekylärbiologi (Medicinska fakulteten),Hultmark(Swepub:umu)dahu0001 (author)
  • Parikka, Mataleena (author)
  • Rämet, Mika (author)
  • University of TampereHultmark (creator_code:org_t)

Related titles

  • In:Journal of Immunology: The American Association of Immunologists184:11, s. 6188-61980022-17671550-6606

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