KMID : 0578320100300060527
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Molecules and Cells 2010 Volume.30 No. 6 p.527 ~ p.532
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Regulation of IkappaB Kinase by G¥âL through Recruitment of the Protein Phosphatases
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You Dong-Joo
Kim You-Lim Park Cho-Rong Kim Dong-Kyu Yeom Jeong-Hun Ahn Curie Seong Jae-Young Hwang Jong-Ik
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Abstract
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G protein ¥â-like (G¥âL) is a member of WD repeat-con-taining family which are involved in various intracellular signaling events. In our previous report, we demon-strated that G¥âL regulates TNF¥á-stimulated NF-¥êB signaling by interacting with and inhibiting phosphorylation of I¥êB kinase. However, G¥âL 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 G¥âL. We also found that G¥âL interacts with PP2A and PP6, other members of the same phosphatase family. By interacting with protein phosphatases, which do not directly bind to IKK¥â, G¥âL mediates the association of phosphatases with IKK¥â. Overexpression of protein phosphatases inhibited TNF¥ê-induced acti-vation of NF-¥êB signaling, which is an effect similar to that of G¥âL overexpression. Down-regulation of G¥âL by small interfering RNA diminished the inhibitory effect of phosphatases, resulting in restoration of NF-¥êB signaling. Thus, we propose that G¥âL functions as a negative regulator of NF-¥êB signaling by recruiting pro-tein phosphatases to the IKK complex.
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KEYWORD
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G¥âL, I¥êB kinase, NF-¥êB, phosphorylation, protein phosphatases
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