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, Daijyu Ichikawa, Naomi Yoshida, Eriko Yokota, 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

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Focal Adhesion Protein-Tyrosine Kinases
Dactinomycin
Cell Survival
Cells
Death Domain Receptor Signaling Adaptor Proteins
Receptors, Tumor Necrosis Factor, Type I
TNF Receptor-Associated Factor 2
Chemical activation
Proteins
Caspase 8
Cell death
Fibroblasts
Cell Adhesion
Assays
Cell Death
Apoptosis

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Focal adhesion kinase determines the fate of death or survival of cells in response to TNFα in the presence of actinomycin D. / Takahashi, Reiko; Sonoda, Yoshiko; Ichikawa, Daijyu; Yoshida, Naomi; Yokota, Eriko; Tadashi, Kasahara.

In: Biochimica et Biophysica Acta - General Subjects, Vol. 1770, No. 4, 04.2007, p. 518-526.

Research output: Contribution to journalArticle

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