A suppressive role of p125FAK protein tyrosine kinase in hydrogen peroxide-induced apoptosis of T98G cells.
Protein tyrosine phosphorylation was examined on a human glioblastoma cell line, T98G, after exposure to oxidative stress in vitro. Hydrogen peroxide (1 mM) markedly induced tyrosine phosphorylation of a 125 kDa protein at 30 min after stimulation. The 125-kDa molecule phosphorylated was revealed to be a focal adhesion kinase (FAK). Tyrosine phosphorylation of p125FAK continued at least up to 5 h, and decreased after 8 h concomitant with apoptosis. Tyrosine phosphorylation of p125FAK was blocked by herbimycin A, a potent inhibitor of protein tyrosine kinases, while apoptosis was accelerated. When T98G cells were incubated with FAK antisense oligonucleotide, apoptosis was also accelerated. These results suggest that tyrosine phosphorylation of p125FAK plays a suppressive role in hydrogen peroxide-induced apoptosis.
Sonoda
Y
Y
Kyoritsu College of Pharmacy, Tokyo, Japan.
Kasahara
T
T
Yokota-Aizu
E
E
Ueno
M
M
Watanabe
S
S
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D016227:Benzoquinones; D015815:Cell Adhesion Molecules / Q000502:physiology*; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D005909:Glioblastoma / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D047029:Lactams, Macrocyclic; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D011505:Protein-Tyrosine Kinases / Q000502:physiology*; D011809:Quinones / Q000494:pharmacology; D017828:Rifabutin / Q000031:analogs & derivatives; D013873:Thionucleotides / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000378:metabolism
D000903:Antibiotics, Antineoplastic; D016227:Benzoquinones; D015815:Cell Adhesion Molecules; D047029:Lactams, Macrocyclic; D016376:Oligonucleotides, Antisense; D011809:Quinones; D013873:Thionucleotides; D017828:Rifabutin; D014443:Tyrosine; C020754:herbimycin; D006861:Hydrogen Peroxide; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496050:PTK2 protein, human