The effect of KN-62, Ca2+/calmodulin dependent protein kinase II inhibitor on cell cycle.
The isoquinolinesulfonamide derivative, KN-62, is a potent and specific inhibitor of Ca2+/calmodulin dependent protein kinase II (CaM kinase II) (Tokumitsu, H., Chijiwa, T., Hagiwara, M., Mizutani, A., Terasawa, M., and Hidaka, H.(1990) J. Biol. Chem. 265, 4315-4320). KN-62 inhibits growth of K562 cells, in a dose-dependent manner. Flow cytometric analysis demonstrates that the treatment of K562 cells with 10 microM KN-62 causes an accumulation of cells in S phase. Immunoblotting studies showed that specific antibodies against CaM kinase II recognized the 65 kDa of protein in K562 cells. This protein showed protein kinase activity as examined by the activity gel method. The inhibition of this enzyme activity by KN-62 was dose-dependent. The immunoprecipitates with the antibodies from K562 cells phosphorylates the synthetic peptide substrates, syntide-2. These results suggest that CaM kinase II plays an important role in the mechanisms for the cell growth in K562 cells.
Minami
H
H
Department of Pharmacology, Nagoya University School of Medicine, Japan.
Inoue
S
S
Hidaka
H
H
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors* / Q000302:isolation & purification; D002453:Cell Cycle / Q000187:drug effects*; D006801:Humans; D066298:In Vitro Techniques; D007546:Isoquinolines / Q000494:pharmacology*; D004915:Leukemia, Erythroblastic, Acute; D010879:Piperazines / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D007546:Isoquinolines; D010879:Piperazines; C063302:KN 62; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases