Staurosporine: an effective inhibitor for Ca2+/calmodulin-dependent protein kinase II.
We investigated the effect of staurosporine on Ca2+/calmodulin-dependent protein kinase II (CaM kinase II) purified from rat brain. (a) Staurosporine (10-100 nM) inhibited the activity of CaM kinase II. The half-maximal and maximal inhibitory concentrations were 20 and 100 nM, respectively. (b) The inhibition with staurosporine was of the noncompetitive type with respect to ATP, calmodulin, and phosphate acceptor (beta-casein). (c) Staurosporine suppressed the auto-phosphorylation of alpha- and beta-subunits of CaM kinase II at concentrations similar to those at which the enzyme activity was inhibited. (d) Staurosporine also attenuated the Ca2+/calmodulin-independent activity of the autophosphorylated CaM kinase II. These results suggest that staurosporine inhibits CaM kinase II by interacting with the catalytic domain, distinct from the ATP-binding site or substrate-binding site, of the enzyme and that staurosporine is an effective inhibitor for CaM kinase II in the cell system.
Yanagihara
N
N
Department of Pharmacology, University of Occupational and Environmental Health, School of Medicine, Kitakyushu, Japan.
Tachikawa
E
E
Izumi
F
F
Yasugawa
S
S
Yamamoto
H
H
Miyamoto
E
E
D000255:Adenosine Triphosphate / Q000378:metabolism; D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D001665:Binding Sites; D001921:Brain / Q000201:enzymology*; D002118:Calcium / Q000494:pharmacology; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D002147:Calmodulin / Q000494:pharmacology; D002364:Caseins / Q000378:metabolism; D002384:Catalysis; D004789:Enzyme Activation / Q000187:drug effects; D007700:Kinetics; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases / Q000378:metabolism; D051381:Rats; D019311:Staurosporine
D000470:Alkaloids; D002147:Calmodulin; D002364:Caseins; D047428:Protein Kinase Inhibitors; D000255:Adenosine Triphosphate; D011494:Protein Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D019311:Staurosporine; D002118:Calcium