Staurosporine: an effective inhibitor for Ca2+/calmodulin-dependent protein kinase II

J Neurochem. 1991 Jan;56(1):294-8. doi: 10.1111/j.1471-4159.1991.tb02595.x.


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.

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Alkaloids / pharmacology*
  • Animals
  • Binding Sites
  • Brain / enzymology*
  • Calcium / pharmacology
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Calmodulin / pharmacology
  • Caseins / metabolism
  • Catalysis
  • Enzyme Activation / drug effects
  • Kinetics
  • Phosphorylation
  • Protein Kinase Inhibitors*
  • Protein Kinases / metabolism
  • Rats
  • Staurosporine


  • Alkaloids
  • Calmodulin
  • Caseins
  • Protein Kinase Inhibitors
  • Adenosine Triphosphate
  • Protein Kinases
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Staurosporine
  • Calcium