Regulation of IκB kinase by GβL through recruitment of the protein phosphatases

Dong Joo You, You Lim Kim, Cho Rong Park, Dong Kyu Kim, Jeonghun Yeom, Cheolju Lee, Curie Ahn, Jae Young Seong, Jong Ik Hwang

    Research output: Contribution to journalArticlepeer-review

    15 Citations (Scopus)

    Abstract

    G protein β-like (GβL) is a member of WD repeat-containing family which are involved in various intracellular signaling events. In our previous report, we demonstrated that GβL regulates TNFα-stimulated NF-κB signaling by interacting with and inhibiting phosphorylation of IκB kinase. However, GβL itself does not seem to regulate IKK directly, because it contains no functional domains except WD domains. Here, using immunoprecipitation and proteomic analyses, we identified protein phosphatase 4 as a new binding partner of GβL. We also found that GβL interacts with PP2A and PP6, other members of the same phosphatase family. By interacting with protein phosphatases, which do not directly bind to IKKβ, GβL mediates the association of phosphatases with IKKβ. Overexpression of protein phosphatases inhibited TNFκ-induced activation of NF-κB signaling, which is an effect similar to that of GβL overexpression. Down-regulation of GβL by small interfering RNA diminished the inhibitory effect of phosphatases, resulting in restoration of NF-κB signaling. Thus, we propose that GβL functions as a negative regulator of NF-κB signaling by recruiting protein phosphatases to the IKK complex.

    Original languageEnglish
    Pages (from-to)527-532
    Number of pages6
    JournalMolecules and cells
    Volume30
    Issue number6
    DOIs
    Publication statusPublished - 2010 Dec

    Keywords

    • GβL
    • IκB kinase
    • NF-κB
    • Phosphorylation
    • Protein phosphatases

    ASJC Scopus subject areas

    • Molecular Biology
    • Cell Biology

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