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Staurosporine: An Effective Inhibitor for Ca 2+ /Calmodulin‐Dependent Protein Kinase II
Author(s) -
Yanagihara Nobuyuki,
Tachikawa Eiichi,
Izumi Futoshi,
Yasugawa Setsuko,
Yamamoto Hideyuki,
Miyamoto Eishichi
Publication year - 1991
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1991.tb02595.x
Subject(s) - staurosporine , autophosphorylation , protein kinase a , calmodulin , kinase , protein kinase inhibitor , biochemistry , microbiology and biotechnology , chemistry , biology , enzyme
We investigated the effect of staurosporine on Ca 2+ /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 (β‐casein). (c) Staurosporine suppressed the autophosphorylation of α‐ and β‐subunits of CaM kinase II at concentrations similar to those at which the enzyme activity was inhibited. (d) Staurosporine also attenuated the Ca 2+ 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.