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.
Zhong
Minghao
M
Department of Biological Sciences, Hunter College of The City University of New York, NY 10021, USA.
Lu
Zhimin
Z
Foster
David A
DA
D000818:Animals; D017209:Apoptosis; D053453:Caspase 9; D020169:Caspases / Q000502:physiology; D002460:Cell Line; D002461:Cell Line, Transformed; D002470:Cell Survival; D016895:Culture Media, Serum-Free; D003574:Cytochrome c Group / Q000502:physiology; D015536:Down-Regulation; D007527:Isoenzymes / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D011493:Protein Kinase C / Q000378:metabolism*; D051745:Protein Kinase C-delta; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D051057:Proto-Oncogene Proteins c-akt; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D053453:Caspase 9; D020169:Caspases; D016895:Culture Media, Serum-Free; D003574:Cytochrome c Group; D007527:Isoenzymes; D019869:Phosphatidylinositol 3-Kinases; D011493:Protein Kinase C; D051745:Protein Kinase C-delta; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D016392:Proto-Oncogene Proteins pp60(c-src); D013755:Tetradecanoylphorbol Acetate; C497260:Prkcd protein, rat; C494920:Akt1 protein, rat; C506435:Casp9 protein, rat