Role of protein kinase C delta in reactivation of Kaposi's sarcoma-associated herpesvirus.
TPA (12-O-tetradecanoylphorbol-13-acetate), a well-known activator of protein kinase C (PKC), can experimentally induce reactivation of Kaposi's sarcoma-associated herpesvirus (KSHV) in certain latently infected cells. We selectively blocked the activity of PKC isoforms by using GF 109203X or rottlerin and demonstrated that this inhibition largely decreased lytic KSHV reactivation by TPA. Translocation of the PKCdelta isoform was evident shortly after TPA stimulation. Overexpression of the dominant-negative PKCdelta mutant supported an essential role for the PKCdelta isoform in virus reactivation, yet overexpression of PKCdelta alone was not sufficient to induce lytic reactivation of KSHV, suggesting that additional signaling molecules participate in this pathway.
Faculty of Life Sciences, Bar-Ilan University, Ramat Gan 52900, Israel.
Einat
E
Deutsch
Adina
A
Cohen
Gila
G
Kazimirsky
Sara
S
Dovrat
Hadara
H
Rubinfeld
Chaya
C
Brodie
Ronit
R
Sarid
D000098:Acetophenones / Q000494:pharmacology; D001578:Benzopyrans / Q000494:pharmacology; D002460:Cell Line; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019288:Herpesvirus 8, Human / Q000187:drug effects / Q000472:pathogenicity / Q000502:physiology*; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D008301:Maleimides / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D051745:Protein Kinase C-delta; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014775:Virus Activation / Q000187:drug effects; D017735:Virus Latency / Q000187:drug effects
D000098:Acetophenones; D001578:Benzopyrans; D004791:Enzyme Inhibitors; D007211:Indoles; D008301:Maleimides; C085746:rottlerin; C497258:PRKCD protein, human; D011493:Protein Kinase C; D051745:Protein Kinase C-delta; C070515:bisindolylmaleimide I; D013755:Tetradecanoylphorbol Acetate