Focal adhesion kinase determines the fate of death or survival of cells in response to TNFα in the presence of actinomycin D

Reiko Takahashi, Yoshiko Sonoda, Daiju Ichikawa, Naomi Yoshida, Aizu Yokota Eriko, Kasahara Tadashi

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

We speculated that focal adhesion kinase (FAK) might play a critical role in the TNFα-induced cell death. In this study, we found that FAK-/- cells are more sensitive to TNFα-induced apoptosis in the presence of actinomycin D (Act D) compared to FAK+/- cells. Prosurvival pathways are activated by the rapid recruitment of complex I, comprising TNFR1, TRADD, RIP and TRAF2, which leads to the activation of the NF-κB pathway. On the other hand, proapoptotic pathways are activated by complex II, the death-inducing signaling complex (DISC), which contains TNFR1, TRADD, RIP, and FADD, and procaspase-8 proteins. As TNFR1, TRADD, and RIP are included in both Complex I and DISC, we speculated that RIP might be a key protein. Coimmunoprecipitation assays revealed that RIP is included in complex I in FAK+/- cells, and FAK was associated with RIP. On the other hand, RIP is included in DISC in FAK-/- cells. FAK might be a key protein in the formation of complex I and the activation of NF-κB. Furthermore, Akt was activated in FAK+/- cells, but not FAK-/- cells. In conclusion, we first demonstrated that FAK determines the pathway leading to death or survival in TNFα/ActD-stimulated fibroblasts.

Original languageEnglish
Pages (from-to)518-526
Number of pages9
JournalBiochimica et Biophysica Acta - General Subjects
Volume1770
Issue number4
DOIs
Publication statusPublished - 2007 Apr 1

Keywords

  • Apoptosis
  • DISC
  • FAK
  • NF-κB
  • RIP
  • TNFα

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology

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