Abstract
3Y1 rat fibroblasts overexpressing the tyrosine kinase c-Src (3Y1c-Src cells) become transformed by downregulation of protein kinase C δ (PKC δ). However, when 3Y1c-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 δ was downregulated, the apoptotic phenotypes induced by serum withdrawal in the 3Y1c-Src cells were suppressed. The apparent survival signal generated by PKC δ 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 δ provides a novel PI3K/Akt-independent survival signal capable of suppressing apoptotic signals.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1071-1078 |
| Number of pages | 8 |
| Journal | Oncogene |
| Volume | 21 |
| Issue number | 7 |
| DOIs | |
| State | Published - Feb 7 2002 |
| Externally published | Yes |
Bibliographical note
Funding Information:We thank Steve Martin for communicating results prior to publication. The dominant negative PKC d mutant was generously provided by Shigeo Ohno. We thank Dongming Cai and Rebecca James for comments on the manuscript. This investigation was supported by National Institutes of
Keywords
- Apoptosis
- c-Src
- PKC δ
- TPA
- Tumor promoter
