Protein Phosphatase 2Cβ Association with the IκB Kinase Complex is Involved in Regulating NF-κB Activity

Shashi Prajapati, Udit Verma, Yumi Yamamoto, Youn Tae Kwak, Richard B. Gaynor

Research output: Contribution to journalArticle

66 Citations (Scopus)

Abstract

The NF-κB pathway is important in the control of the immune and inflammatory response. One of the critical events in the activation of this pathway is the stimulation of the IκB kinases (IKKs) by cytokines such as tumor necrosis factor-α and interleukin-1. Although the mechanisms that modulate IKK activation have been studied in detail, much less is known about the processes that down-regulate its activity following cytokine treatment. In this study, we utilized biochemical fractionation and mass spectrometry to demonstrate that protein phosphatase 2Cβ (PP2Cβ) can associate with the IKK complex. PP2Cβ association with the IKK complex led to the dephosphorylation of IKKβ and decreased its kinase activity. The binding of PP2Cβ to IKKβ was decreased at early times post-tumor necrosis factor-α treatment and was restored at later times following treatment with this cytokine. Experiments utilizing siRNA directed against PP2Cβ demonstrated an in vivo role for this phosphatase in decreasing IKK activity at late times following cytokine treatment. These studies are consistent with the ability of PP2Cβ to down-regulate cytokine-induced NF-κB activation by altering IKK activity.

Original languageEnglish (US)
Pages (from-to)1739-1746
Number of pages8
JournalJournal of Biological Chemistry
Volume279
Issue number3
DOIs
StatePublished - Jan 16 2004

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Phosphoprotein Phosphatases
Phosphotransferases
Cytokines
Chemical activation
Down-Regulation
Tumor Necrosis Factor-alpha
Fractionation
Interleukin-1
Phosphoric Monoester Hydrolases
Small Interfering RNA
Mass spectrometry
Mass Spectrometry
Carrier Proteins
Protein Phosphatase 2C
Association reactions
Experiments

ASJC Scopus subject areas

  • Biochemistry

Cite this

Protein Phosphatase 2Cβ Association with the IκB Kinase Complex is Involved in Regulating NF-κB Activity. / Prajapati, Shashi; Verma, Udit; Yamamoto, Yumi; Kwak, Youn Tae; Gaynor, Richard B.

In: Journal of Biological Chemistry, Vol. 279, No. 3, 16.01.2004, p. 1739-1746.

Research output: Contribution to journalArticle

Prajapati, Shashi ; Verma, Udit ; Yamamoto, Yumi ; Kwak, Youn Tae ; Gaynor, Richard B. / Protein Phosphatase 2Cβ Association with the IκB Kinase Complex is Involved in Regulating NF-κB Activity. In: Journal of Biological Chemistry. 2004 ; Vol. 279, No. 3. pp. 1739-1746.
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