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 journalArticle

10 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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