Suppression of ultraviolet irradiation-induced apoptosis by overexpression of focal adhesion kinase in Madin-Darby canine kidney cells

Po Chao Chan, Jui Fen Lai, Chi Hung Cheng, Ming Jer Tang, Chia Chieh Chiu, Hong Chen Chen

Research output: Contribution to journalArticle

99 Citations (Scopus)

Abstract

Focal adhesion kinase (FAK) has been implicated to play a role in suppression of apoptosis. In this study, we have demonstrated that UV irradiation induced cleavage of FAK and two of its interacting proteins Src and p130(Cas) in Madin-Darby canine kidney cells, concomitant with an increase in cell death. The cleavage of these proteins upon UV irradiation was completely inhibited by ZVAD-FMK, a broad range inhibitor of caspases, and apparently delayed by Bcl2 overexpression. To examine if FAK plays a role in suppressing UV-induced apoptosis, stable Madin-Darby canine kidney cell lines overexpressing FAK were established. Our results showed that a marked (30-40%) increase in cell survival upon UV irradiation was achieved by this strategy. In our efforts to determine the mechanism by which FAK transduces survival signals to the downstream, we found that a FAK mutant deficient in binding to phosphatidylinositol 3-kinase failed to promote cell survival. Moreover, the expression of the Src hornology 3 domain of p130(Cas), which competed with endogenous p130(Cas) for FAK binding, abrogated the FAK- promoted cell survival. Together, these results suggest that the integrity of FAK and its binding to phosphatidylinositol 3-kinase and p130(Cas) are required for FAK to exert its antiapoptotic function.

Original languageEnglish
Pages (from-to)26901-26906
Number of pages6
JournalJournal of Biological Chemistry
Volume274
Issue number38
DOIs
Publication statusPublished - 1999 Sep 17

    Fingerprint

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this