Downregulating PKC δ provides a PI3K/Akt-independent survival signal that overcomes apoptotic signals generated by c-Src overexpression

被引:41
作者
Zhong, MH [1 ]
Lu, ZM [1 ]
Foster, DA [1 ]
机构
[1] CUNY Hunter Coll, Dept Biol Sci, New York, NY 10021 USA
关键词
apoptosis; c-Src; PKC delta; tumor promoter; TPA;
D O I
10.1038/sj.onc.1205165
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
3Y1 rat fibroblasts overexpressing the tyrosine kinase c-Src (3Y1(c-Src) cells) become transformed by downregulation of protein kinase C delta (PKC delta). However, when 3Y1(c-Src) cells were subjected to serum withdrawal, they underwent apoptosis via a cytochrome c/caspase 9 pathway. In contrast, neither parental nor v-Src-transformed 3Y1 cells underwent apoptosis when subjected to serum withdrawal. If PKC delta was downregulated, the apoptotic phenotypes induced by serum withdrawal in the 3Y1(c-Src) cells were suppressed. The apparent survival signal generated by PKC delta downregulation was independent of the phosphatidylinositol-3-kinase (PI3K)/Akt survival pathway. Collectively, these data indicate that (1) c-Src overexpression renders cells sensitive to apoptotic stress, and (2) that downregulation of PKC delta provides a novel PI3K/Akt-independent survival signal capable of suppressing apoptotic signals.
引用
收藏
页码:1071 / 1078
页数:8
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