Direction of p21ras-generated signals towards cell growth or apoptosis is determined by protein kinase C and Bcl-2.
Normal and activated Ras proteins are known to act as signal transducers, mediating mitogenic responses. Interactions of p21ras and protein kinase C (PKC) are required in a number of mitogenic or activation signaling pathways. The constitutive expression of activated v-Haras in Jurkat cells, a human T lymphoblastoid cell line, renders the cells susceptible to apoptosis during transient down-regulation or inhibition of PKC. Similarly, the expression of v-Ki-ras in murine fibroblasts induces apoptosis during suppression of PKC activity. This Ras-specific cell death is dependent upon suppression of cellular PKC activity, and can be blocked by the survival-promoting bcl-2 gene product. In vivo phosphorylation studies indicate that Bcl-2 is a phosphoprotein, and the phosphorylation state of Bcl-2 is modulated in the setting of activated p21Ha-ras in response to inhibition of PKC. These findings suggest an interactive regulation of growth or apoptosis in cells which involves at least three molecules: p21ras, PKC and Bcl-2.
D017209:Apoptosis; D002118:Calcium / Q000502:physiology; D002455:Cell Division; D003513:Cycloheximide / Q000494:pharmacology; D015536:Down-Regulation; D004789:Enzyme Activation / Q000187:drug effects; D006133:Growth Substances / Q000502:physiology; D006801:Humans; D010766:Phosphorylation; D011493:Protein Kinase C / Q000502:physiology*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2; D016283:Proto-Oncogene Proteins p21(ras) / Q000502:physiology*; D015398:Signal Transduction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D006133:Growth Substances; D011500:Protein Synthesis Inhibitors; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D003513:Cycloheximide; D011493:Protein Kinase C; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras); D013755:Tetradecanoylphorbol Acetate; D002118:Calcium