Tumor necrosis factor-induced nuclear factor κB activation is impaired in focal adhesion kinase-deficient fibroblasts

Megumi Funakoshi-Tago, Yoshiko Sonoda, Saeko Tanaka, Kenichiro Hashimoto, Kenji Tago, Shin ichi Tominaga, Tadashi Kasahara

Research output: Contribution to journalArticlepeer-review

55 Citations (Scopus)


Focal adhesion kinase (FAK) is widely involved in important cellular functions such as proliferation, migration, and survival, although its roles in immune and inflammatory responses have yet to be explored. We demonstrate a critical role for FAK in the tumor necrosis factor (TNF)-induced activation of nuclear factor (NF)-κB, using FAK-deficient (FAK-/-) embryonic fibroblasts. Interestingly, TNF-induced interleukin (IL)-6 production was nearly abolished in FAK-/- fibroblasts, whereas a normal level of production was obtained in FAK+/- or FAK+/+ fibroblasts. FAK deficiency did not affect the three types of mitogen-activated protein kinases, ERK, JNK, and p38. Similarly, TNF-induced activation of activator protein 1 or NF-IL-6 was not impaired in FAK-/- cells. Of note, TNF-induced NFκB DNA binding activity and activation of IκB kinases (IKKs) were markedly impaired in FAK-/- cells, whereas the expression of TNF receptor I or other signaling molecules such as receptor-interacting protein (RIP), tumor necrosis factor receptor-associated factor 2 (TRAF2), IKKα, IKKβ, and IKKγ was unchanged. Also, TNF-induced association of FAK with RIP and subsequent association of RIP with TRAF2 were not observed, resulting in a failure of RIP to recruit the IKK complex in FAK-/- cells. The reintroduction of wild type FAK into FAK-/- cells restored the interaction of RIP with TRAF2 and the IKK complex and allowed recovery of NF-κB activation and subsequent IL-6 production. Thus, we propose a novel role for FAK in the NF-κB activation pathway leading to the production of cytokines.

Original languageEnglish
Pages (from-to)29359-29365
Number of pages7
JournalJournal of Biological Chemistry
Issue number31
Publication statusPublished - 2003 Aug 1

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


Dive into the research topics of 'Tumor necrosis factor-induced nuclear factor κB activation is impaired in focal adhesion kinase-deficient fibroblasts'. Together they form a unique fingerprint.

Cite this