Potent and preferential inhibition of Ca2+/calmodulin-dependent protein kinase II by K252a and its derivative, KT5926.
Effects of protein kinase inhibitors, K252a and its derivative KT5926, on Ca2+/calmodulin-dependent protein kinase II were examined. Both compounds potently inhibited Ca2+/calmodulin-dependent protein kinase II. Kinetic analyses indicated that the inhibitory effect of K252a and KT5926 was competitive with respect to ATP (Ki: 1.8 and 4.4 nM, respectively) and noncompetitive with respect to the substrates. Taken together with a previous report (Nakanishi et al. Mol. Pharmacol. 37, 482, 1990) concerning the Ki values of these compounds for ATP with various protein kinases, the results suggest that K252a and KT5926 are potent and preferential inhibitors of Ca2+/calmodulin-dependent protein kinase II.
Hashimoto
Y
Y
First Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.
Nakayama
T
T
Teramoto
T
T
Kato
H
H
Watanabe
T
T
Kinoshita
M
M
Tsukamoto
K
K
Tokunaga
K
K
Kurokawa
K
K
Nakanishi
S
S
D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D002227:Carbazoles / Q000494:pharmacology*; D026121:Indole Alkaloids; D007211:Indoles; D007700:Kinetics; D009219:Myosin-Light-Chain Kinase / Q000037:antagonists & inhibitors; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D047428:Protein Kinase Inhibitors
D000470:Alkaloids; D002227:Carbazoles; D026121:Indole Alkaloids; D007211:Indoles; D047428:Protein Kinase Inhibitors; C063769:KT 5926; C049985:staurosporine aglycone; D011493:Protein Kinase C; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D009219:Myosin-Light-Chain Kinase