Gene interactions and pathways from curated databases and text-mining
J Biol Chem 2004, PMID: 14585847

Protein phosphatase 2Cbeta association with the IkappaB kinase complex is involved in regulating NF-kappaB activity.

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

The NF-kappaB 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 IkappaB kinases (IKKs) by cytokines such as tumor necrosis factor-alpha 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 2Cbeta (PP2Cbeta) can associate with the IKK complex. PP2Cbeta association with the IKK complex led to the dephosphorylation of IKKbeta and decreased its kinase activity. The binding of PP2Cbeta to IKKbeta was decreased at early times post-tumor necrosis factor-alpha treatment and was restored at later times following treatment with this cytokine. Experiments utilizing siRNA directed against PP2Cbeta 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 PP2Cbeta to down-regulate cytokine-induced NF-kappaB activation by altering IKK activity.

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Text Mining Data

NF-kappaB — IkappaB kinase complex: " Protein phosphatase 2Cbeta association with the IkappaB kinase complex is involved in regulating NF-kappaB activity "

Manually curated Databases

  • OpenBEL Selventa BEL large corpus: CHUK → TNF (increases, TNF Activity)
    Evidence: The NF-kappaB 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 IkappaB kinases (IKKs) by cytokines such as tumor necrosis factor-alpha and interleukin-1.
  • OpenBEL Selventa BEL large corpus: IKBKB → TNF (increases, TNF Activity)
    Evidence: The NF-kappaB 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 IkappaB kinases (IKKs) by cytokines such as tumor necrosis factor-alpha and interleukin-1.
  • OpenBEL Selventa BEL large corpus: PPM1B → TNF (decreases, TNF Activity)
    Evidence: The binding of PP2Cbeta to IKKbeta was decreased at early times post-tumor necrosis factor-alpha treatment and was restored at later times following treatment with this cytokine.
  • OpenBEL Selventa BEL large corpus: IKBKB → IL1A (increases, IL1A Activity)
    Evidence: The NF-kappaB 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 IkappaB kinases (IKKs) by cytokines such as tumor necrosis factor-alpha and interleukin-1.
  • OpenBEL Selventa BEL large corpus: IKBKB → IL1B (increases, IL1B Activity)
    Evidence: The NF-kappaB 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 IkappaB kinases (IKKs) by cytokines such as tumor necrosis factor-alpha and interleukin-1.
  • IRef Biogrid Interaction: PPM1B — IKBKG (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: CHUK — PPM1B (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: IKBKB — PPM1B (direct interaction, enzymatic study)
  • IRef Biogrid Interaction: IKBKB — PPM1B (physical association, affinity chromatography technology)
  • IRef Hprd Interaction: PPM1B — IKBKG (in vivo)
  • IRef Hprd Interaction: IKBKB — PPM1B (in vitro)
  • IRef Hprd Interaction: IKBKB — PPM1B (in vivo)
In total, 3 gene pairs are associated to this article in curated databases