Antiapoptotic action of focal adhesion kinase (FAK) against ionizing radiation

Tadashi Kasahara, Emiko Koguchi, Megumi Tago, Eriko Yokota, Yoshiko Sonoda

Research output: Contribution to journalArticle

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Abstract

Focal adhesion kinase (FAK) has an antiapoptotic role in anchorage-dependent cells via an unknown mechanism. To elucidate the role of FAK in the antiapoptosis, we have demonstrated that FAK-overexpressed (HL-60/FAK) cells have marked resistance against various apoptotic stimuli. That is, HL-60/FAK cells were highly resistant to hydrogen peroxide or etoposide-induced apoptosis compared with the vector-transfected cells. In this study, we demonstrated that HL-60/FAK cells were highly resistant to ionizing radiation (IR)-induced apoptosis. IR at 10-40 Gy induced significant DNA fragmentation, activation of caspase-3 and -8, the processing of a proapoptotic BID, and mitochondrial release of cytochrome c in the parental or HL-60/Vect cells, whereas no significant DNA fragmentation or no other concurring events were observed in the HL-60/FAK cells. Of note is that, in the HL-60/FAK cells, phosphatidylinositol 3′-kinase-Akt survival pathway was activated, accompanied with significant induction of inhibitor-of-apoptosis proteins (cIAP-2, XIAP). Finally, constructs of FAK mutants revealed that the central kinase domain (K454), autophosphorylation site (Y397), as well as focal adhesion target regions (Y925), were prerequisite for the FAK function. These results indicated that mitochondria pathway is required for IR-induced apoptosis, and FAK overexpression prevents this pathway, thus rendering antiapoptotic states.

Original languageEnglish
Pages (from-to)491-499
Number of pages9
JournalAntioxidants and Redox Signaling
Volume4
Issue number3
Publication statusPublished - 2002

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Focal Adhesion Protein-Tyrosine Kinases
Ionizing radiation
Ionizing Radiation
DNA Fragmentation
Apoptosis
Phosphatidylinositol 3-Kinase
Inhibitor of Apoptosis Proteins
Mitochondria
Focal Adhesions
Caspase 8
HL-60 Cells
DNA
Etoposide
Cytochromes c
Caspase 3
Hydrogen Peroxide
Phosphotransferases
Adhesion
Chemical activation

ASJC Scopus subject areas

  • Biochemistry

Cite this

Antiapoptotic action of focal adhesion kinase (FAK) against ionizing radiation. / Kasahara, Tadashi; Koguchi, Emiko; Tago, Megumi; Yokota, Eriko; Sonoda, Yoshiko.

In: Antioxidants and Redox Signaling, Vol. 4, No. 3, 2002, p. 491-499.

Research output: Contribution to journalArticle

Kasahara, Tadashi ; Koguchi, Emiko ; Tago, Megumi ; Yokota, Eriko ; Sonoda, Yoshiko. / Antiapoptotic action of focal adhesion kinase (FAK) against ionizing radiation. In: Antioxidants and Redox Signaling. 2002 ; Vol. 4, No. 3. pp. 491-499.
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