Opposing effects of protein kinase C delta and protein kinase B alpha on H(2)O(2)-induced apoptosis in CHO cells.
H(2)O(2)-induced apoptosis was enhanced in the CHO cell line overproducing protein kinase C delta (PKCdelta) as judged by DNA fragmentation. In response to the H(2)O(2) treatment, PKCdelta was tyrosine phosphorylated and recovered as a constitutively active form, but its proteolytic fragment was not generated. In contrast, H(2)O(2)-induced apoptosis was suppressed in the CHO cell line overexpressing protein kinase B alpha (PKBalpha). Consistently, phosphorylation of BAD, a pro-apoptotic protein negatively regulated by PKBalpha, was sustained in the cells overproducing PKBalpha, but was not changed in the cells overexpressing PKCdelta. In the CHO cell line overproducing both PKCdelta and PKBalpha, H(2)O(2)-induced tyrosine phosphorylation of PKCdelta was suppressed, and DNA fragmentation was diminished concomitantly. These results suggest that PKCdelta contributes to H(2)O(2)-induced apoptosis by a mechanism independent of BAD and that PKCdelta is a target of PKB for the regulation of cell survival.
Konishi
H
H
Faculty of Science, Kobe University, Kobe, 657-8501, Japan.
Matsuzaki
H
H
Takaishi
H
H
Yamamoto
T
T
Fukunaga
M
M
Ono
Y
Y
Kikkawa
U
U
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D016466:CHO Cells / Q000201:enzymology* / Q000473:pathology*; D006224:Cricetinae; D053938:DNA Fragmentation; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D007527:Isoenzymes / Q000378:metabolism*; D016877:Oxidants / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism*; D051745:Protein Kinase C-delta; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D015398:Signal Transduction / Q000187:drug effects
D007527:Isoenzymes; D016877:Oxidants; D011518:Proto-Oncogene Proteins; D006861:Hydrogen Peroxide; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D011493:Protein Kinase C; D051745:Protein Kinase C-delta