Phosphatase inhibition leads to activation of IκB kinase in murine macrophages

Bruce J. Grossman, Thomas P. Shanley, Alvin G. Denenberg, Bin Zhao, Hector R. Wong*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


We have been interested in elucidating the role of intracellular phosphatase activity in the regulation of immune cell activation. To this end, we treated RAW 264.7 murine macrophages with the phosphatase inhibitor, calyculin-A. Treatment with calyculin-A led to activation of IκB kinase, degradation of IκBα, and induced nuclear translocation and DNA binding of NF-κB. Each of these effects occurred in both a time- and dose-dependent manner. In addition, each of these effects were negatively modulated by prior induction of the heat-shock response. Despite clear activation of the IκB kinase/IκBα/NF-κB pathway, however, phosphatase inhibition did not lead to increased expression of NF-κB-dependent genes. Thus, intracellular phosphatase activity is a central regulator of the NF-κB signal transduction pathway and is negatively modulated by heat shock. Inhibition of intracellular phosphatase activity with calyculin-A is not sufficient to induce NF-κB-dependent gene expression, demonstrating the complexity of NF-κB regulation in immune cells.

Original languageEnglish (US)
Pages (from-to)1264-1269
Number of pages6
JournalBiochemical and Biophysical Research Communications
Issue number5
StatePublished - 2002


  • Inflammation
  • Macrophages
  • Phosphatases
  • Signal transduction
  • Transcription factors

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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