Potentiation of K252a, a protein kinase inhibitor-induced polyploidization by cAMP in cultured fibrosarcoma cell line.
We found that K252a, a potent inhibitor of protein kinases (PK), induced DNA re-replication of Meth-A cells, i.e., DNA synthesis at a higher DNA ploidy without undergoing cytokinesis (polyploidization). The K252a-induced polyploidization was inhibited by phorbol 12-myristate 13-acetate (PMA), a protein kinase C (PKC) activator, suggesting that the polyploidization is caused through inhibition of PKC. By contrast, the polyploidization was potentiated by adenosine 3':5'-cyclic monophosphate (cAMP), a cAMP-dependent protein kinase (PKA) activator. These findings suggest that the cAMP-dependent signaling pathway and diacylglycerol (DAG)-dependent signaling pathway play an important role in regulating the induction of polyploidization in Meth-A cells, through a possible "cross-talk" between the two pathways.
Zong
Z P
ZP
Division of Basic Science, Kanazawa Medical University, Ishikawa, Japan.
Fujikawa-Yamamoto
K
K
Teraoka
K
K
Yamagishi
H
H
Tanino
M
M
Odashima
S
S
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology*; D002227:Carbazoles / Q000494:pharmacology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors*; D003513:Cycloheximide / Q000494:pharmacology; D004247:DNA / Q000096:biosynthesis; D015536:Down-Regulation; D004357:Drug Synergism; D026121:Indole Alkaloids; D051379:Mice; D008807:Mice, Inbred BALB C; D011123:Polyploidy; D015398:Signal Transduction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D002227:Carbazoles; D026121:Indole Alkaloids; D003994:Bucladesine; D000255:Adenosine Triphosphate; D004247:DNA; C049985:staurosporine aglycone; D003513:Cycloheximide; D017868:Cyclic AMP-Dependent Protein Kinases; D013755:Tetradecanoylphorbol Acetate