Rac is activated by tumor necrosis factor α and is involved in activation of Erk

Yurika Nosaka, Ayako Arai, Eiichiro Kanda, Takashi Akasaki, Hideki Sumimoto, Nobuyuki Miyasaka, Osamu Miura

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Tumor necrosis factor α (TNFα) activates various signal transduction pathways including those involving phosphatidylinositol 3-kinase (PI3K), extracellular signal-regulated kinases (Erk), c-Jun N-terminal protein kinases (JNK), and p38 kinases. Using the Rac binding domain of PAK (PAK-RBD) as an activation-specific probe, here we demonstrate that TNFα very rapidly and transiently activates the Rho family GTPase Rac in L929 cells. The PI3K inhibitor LY294002 significantly inhibited TNFα activation of Rac as well as Erk and abolished that of the PI3K target Akt, without showing any inhibitory effects on JNK and p38 activation. Furthermore, TNFα activation of Erk was abolished by a dominant negative Rac mutant, Rac17N, or by an activated Rac mutant, Rac12V. These findings suggest that Rac is activated by a mechanism that is at least partly dependent on PI3K in TNFα stimulated cells and plays a critical role in activation of the Erk signaling pathway.

Original languageEnglish
Pages (from-to)675-679
Number of pages5
JournalBiochemical and Biophysical Research Communications
Volume285
Issue number3
DOIs
Publication statusPublished - Jan 1 2001
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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