| Autor: |
Gruber, Peter, Rechfeld, Florian, Kirchmair, Johannes, Hauser, Nina, Boehler, Markus, Garczarczyk, Dorota, Langer, Thierry, Hofmann, Johann |
| Předmět: |
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| Zdroj: |
Journal of Biochemistry; Mar2011, Vol. 149 Issue 3, p331-336, 6p, 2 Diagrams, 5 Graphs |
| Abstrakt: |
Protein kinase C (PKC) is a family of at least 10 isozymes involved in the activation of different signal transduction pathways. The exact function of these isozymes is not known at present. Isozyme-selective inhibitors would be important to explain the function of the different PKCs and are anticipated to have pharmaceutical potential. Here we report that the small organic molecule BAS 02104951 [5-(1,3-benzodioxol-5-ylmethylene)-1-(phenylmethyl)-2,4,6(1H,3H,5H)-pyrimidinetrion], a barbituric acid derivative, inhibited PKCη and PKCϵ in vitro (IC50 18 and 36 µM, respectively). BAS 02104951 also inhibited the interaction of PKCɛ with its adaptor protein receptor for activated C-kinase 2 (RACK2) (IC50 28.5 µM). BAS 02104951 also inhibited 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced Elk-1 phosphorylation in HeLa cells, translocation of PKCɛ and PKCη to the membrane following treatment of PC3 cells with TPA. The compound did not inhibit the proliferation of PC3 and HeLa cells. BAS 02104951 can be used as selective inhibitor of PKCϵ in cells not expressing PKCη and may serve as a basis for the rational development of a selective inhibitor of PKCϵ or PKCη, or for an inhibitor of the PKCϵ/RACK2 interaction. [ABSTRACT FROM PUBLISHER] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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