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

Tadashi Kasahara, Emiko Koguchi, Megumi Funakoshi, Eriko Aizu-yokota, Yoshiko Sonoda

研究成果: Article査読

73 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)491-499
ページ数9
ジャーナルAntioxidants and Redox Signaling
4
3
DOI
出版ステータスPublished - 2002 1 1

ASJC Scopus subject areas

  • 生化学
  • 生理学
  • 分子生物学
  • 臨床生化学
  • 細胞生物学

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