Antiapoptotic Action of Focal Adhesion Kinase (FAK) Against Ionizing Radiation

Autor: Megumi Funakoshi, Emiko Koguchi, Eriko Aizu-Yokota, Tadashi Kasahara, Yoshiko Sonoda
Rok vydání: 2002
Předmět:
Time Factors
Cell Survival
Physiology
Clinical Biochemistry
Apoptosis
Cytochrome c Group
HL-60 Cells
DNA Fragmentation
Protein Serine-Threonine Kinases
Biology
Models
Biological
Biochemistry
Ionizing radiation
Focal adhesion
Phosphatidylinositol 3-Kinases
chemistry.chemical_compound
Proto-Oncogene Proteins
Serine
Animals
Humans
Phosphatidylinositol
Molecular Biology
General Environmental Science
Cytochrome c
Cell Biology
Protein-Tyrosine Kinases
Neoplasm Proteins
Cell biology
chemistry
Gamma Rays
Caspases
Focal Adhesion Kinase 1
Focal Adhesion Protein-Tyrosine Kinases
biology.protein
Tyrosine
General Earth and Planetary Sciences
DNA fragmentation
biological phenomena
cell phenomena
and immunity
Carrier Proteins
Proto-Oncogene Proteins c-akt
BH3 Interacting Domain Death Agonist Protein
DNA Damage
Zdroj: Antioxidants & Redox Signaling. 4:491-499
ISSN: 1557-7716
1523-0864
DOI: 10.1089/15230860260196290
Popis: 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.
Databáze: OpenAIRE
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