Participation of intracellular Ca(2+)/calmodulin and protein kinase(s) in the pathway of apoptosis induced by a Drosophila cell death gene, reaper.

To elucidate the apoptotic signaling pathway, we have generated a cell culture model: S2 cells stably transfected with a Drosophila cell death gene, reaper (rpr). Following rpr overexpression, caspase activation-mediated apoptotic cell death was induced in the cells. Apoptosis triggered by rpr required intracellular Ca(2+) ions and calmodulin. Furthermore, protein kinase inhibitors H-7 (a PKC, PKA, PKG, MLCK, and CKI inhibitor), calphostin C (a PKC inhibitor), or H-89 (a PKA and PKG inhibitor) completely blocked apoptosis induced by rpr, suggesting that some kind of serine/threonine protein kinase(s) act upstream of caspase in apoptotic pathway induced by rpr in S2 cells.