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

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.