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.
Piao
Z
Z
Department of Pharmacology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo, 113-8602, Japan.
Ui-Tei
K
K
Nagano
M
M
Miyata
Y
Y
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling; D002147:Calmodulin / Q000378:metabolism*; D002460:Cell Line; D004330:Drosophila / Q000166:cytology / Q000378:metabolism*; D029721:Drosophila Proteins; D004533:Egtazic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015870:Gene Expression; D020128:Inhibitory Concentration 50; D010455:Peptides / Q000235:genetics / Q000378:metabolism*; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014162:Transfection
D002147:Calmodulin; D029721:Drosophila Proteins; D004791:Enzyme Inhibitors; D010455:Peptides; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; C086973:rpr protein, Drosophila; D004533:Egtazic Acid; D011494:Protein Kinases; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D002118:Calcium