PROTEIN-KINASE-C INVOLVEMENT IN APOPTOSIS

1. Conflicting observations on the involvement of PKC in apoptosis point to a great variability depending on cell type, agent or condition causing apoptosis, phase of the cell cycle and intracellular signaling pathway. 2. Inhibition by PKC of store-operated calcium entry mechanisms, which are sensitive to the oncoprotein bcl-2, should block the activation of calcium-dependent enzymes triggering the apoptotic cell death. 3. Activation of phosphatases by ceramide and inhibition of PKC by sphingosine seem to mediate the sphingomyelin pathway to apoptosis. 4. A putative target protein appears to be p34(cdc2) which is regulated by a network of kinases and phosphatases. The uncoupling of timing for p34(cdc2) activation and the completion of DNA replication results in the so-called ''mitotic catastrophe'' that shares some features with apoptosis.