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UCN‐01, an anti‐tumor drug, is a selective inhibitor of the conventional PKC subfamily
Author(s) -
Mizuno Keiko,
Noda Kumi,
Ueda Yoshihiko,
Hanaki Hisao,
Saido Takaomi C.,
Ikuta Tohgo,
Kuroki Toshio,
Tamaoki Tatsuya,
Hirai Syu-ichi,
Osada Shin-ichi,
Ohno Shigeo
Publication year - 1995
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(95)00042-8
Subject(s) - isozyme , protein kinase c , calphostin c , staurosporine , subfamily , in vivo , in vitro , microbiology and biotechnology , chemistry , biology , biochemistry , enzyme , genetics , gene
A selective PKC inhibitor, UCN‐01, was shown to exhibit anti‐tumor activity in vitro and in vivo. We investigated UCN‐01 with respect to isozyme‐specific PKC inhibition using purified recombinant or rabbit brain PKC isozymes, cPKCα, β and γ, nPKCδ, ϵ and ν, and aPKCζ. Of the PKC isozymes examined, cPKCα was inhibited by UCN‐01 most effectively ( K i = 0.44 nM), suggesting cPKCα is the prime candidate for the physiological target of UCN‐01. The K i values of UCN‐01 estimated from Dixon plots for cPKC isozymes are approximately 1 nM, whereas the K i values for nPKC isozymes are about 20 nM. Moreover, the K i value for aPKCζ is 3.8 μM. Thus, UCN‐01 discriminates between PKC subfamilies. In addition, the inhibitory effects of staurosporine, H7, and calphostin C on aPKCζ were examined and compared with those for cPKCα.