The regulatory domain of protein kinase Ctheta localises to the Golgi complex and induces apoptosis in neuroblastoma and Jurkat cells.
This study investigates apoptotic effects of protein kinase C (PKC) delta and theta in neuroblastoma cells. 12-O-tetradecanoylphorbol-13-acetate induces apoptosis in SK-N-BE(2) neuroblastoma cells overexpressing PKCdelta or PKCtheta, but not PKC epsilon. The PKC inhibitor GF109203X does not suppress this apoptotic effect, suggesting that it is independent of the catalytic activity of PKC. The isolated catalytic domains of PKCdelta and PKCtheta or the regulatory domain (RD) of PKCtheta also induce apoptosis in neuroblastoma cells. The apoptotic responses are suppressed by caspase inhibition and by Bcl-2 overexpression. The PKCtheta RD induced apoptosis also in Jurkat cells. Colocalisation analysis revealed that the PKCtheta RD primarily localises to the Golgi complex. The C1b domain is required for this localisation and removal of the C1b domain results in a PKCtheta construct that does not induce apoptosis. This suggests that the PKCtheta RD has apoptotic activity and that Golgi localisation may be important for this effect.
Schultz
A
A
Lund University, Molecular Medicine, Entrance 78, 3rd floor, UMAS, 205 02 Malmö, Sweden.
Jönsson
J-I
JI
Larsson
C
C
D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019254:Genes, bcl-2 / Q000235:genetics; D006056:Golgi Apparatus / Q000187:drug effects / Q000201:enzymology*; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019169:Jurkat Cells; D009447:Neuroblastoma / Q000378:metabolism*; D020033:Protein Isoforms / Q000037:antagonists & inhibitors / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051745:Protein Kinase C-delta; D051744:Protein Kinase C-epsilon; D000074121:Protein Kinase C-theta; D017434:Protein Structure, Tertiary / Q000187:drug effects / Q000235:genetics
D061945:Caspase Inhibitors; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D020033:Protein Isoforms; C497258:PRKCD protein, human; C497255:PRKCE protein, human; C076233:PRKCQ protein, human; D011493:Protein Kinase C; D051745:Protein Kinase C-delta; D051744:Protein Kinase C-epsilon; D000074121:Protein Kinase C-theta; D020169:Caspases