Abstract:
: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, cPKC alpha, beta and gamma, nPKC delta, epsilon and eta, and a PKC zeta. Of the PKC isozymes examined, cPKC alpha was inhibited by UCN-01 most effectively (Ki = 0.44 nM), suggesting cPKC alpha is the prime candidate for the physiological target of UCN-01. The Ki values of UCN-01 estimated from Dixon plots for cPKC isozymes are approximately 1 nM, whereas the Ki values for nPKC isozymes are about 20 nM. Moreover, the Ki value for aPKC zeta is 3.8 microM. Thus, UCN-01 discriminates between PKC subfamilies. In addition, the inhibitory effects of staurosporine, H7, and calphostin C on aPKC zeta were examined and compared with those for cPKC alpha.
journal_name
FEBS Lettjournal_title
FEBS lettersauthors
Mizuno K,Noda K,Ueda Y,Hanaki H,Saido TC,Ikuta T,Kuroki T,Tamaoki T,Hirai S,Osada Sdoi
10.1016/0014-5793(95)00042-8subject
Has Abstract,Author List Incompletepub_date
1995-02-13 00:00:00pages
259-61issue
2-3eissn
0014-5793issn
1873-3468journal_volume
359pub_type
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