Stimulation of NFκB activity by multiple signaling pathways requires PAK1

Jeffrey A. Frost, Jennifer L. Swantek, Steven Stippec, Min Jean Yin, Richard Gaynor, Melanie H. Cobb

Research output: Contribution to journalArticle

153 Scopus citations

Abstract

The p21-activated kinase (PAK1) is a serine-threonine protein kinase that is activated by binding to the Rho family small G proteins Rac and Cdc42hs. Both Rac and Cdc42hs have been shown to regulate the activity of the transcription factor NFκB. Here we show that expression of active Ras, Raf- 1, or Rac1 in fibroblasts stimulates NFκB in a PAK1-dependent manner and that expression of active PAK1 can stimulate NFκB on its own. Similarly, in macrophages activation of NFκB as well as transcription from the tumor necrosis factor α promoter depends on PAK1. In these cells lipopolysaccharide is a potent activator of PAK1 kinase activity. We also demonstrate that expression of active PAK1 stimulates the nuclear translocation of the p65 subunit of NFκB but does not activate the inhibitor of κB kinases α or β. These data demonstrate that PAK1 is a crucial signaling molecule involved in NFκB activation by multiple stimuli.

Original languageEnglish (US)
Pages (from-to)19693-19699
Number of pages7
JournalJournal of Biological Chemistry
Volume275
Issue number26
DOIs
StatePublished - Jun 30 2000

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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