Barbituric acid derivative BAS 02104951 inhibits PKC , PKC , PKC /RACK2 interaction, Elk-1 phosphorylation in HeLa and PKC and translocation in PC3 cells following TPA-induction
| Autor: | Florian Rechfeld, Markus Boehler, Johannes Kirchmair, Johann Hofmann, Nina Hauser, Thierry Langer, Dorota Garczarczyk, Peter Gruber |
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| Rok vydání: | 2010 |
| Předmět: |
Protein Kinase C-epsilon
Fluorescent Antibody Technique Biochemistry Isozyme Cell Line HeLa 03 medical and health sciences 0302 clinical medicine Animals Humans Enzyme Inhibitors Phosphorylation Receptor Molecular Biology Protein Kinase C Protein kinase C ets-Domain Protein Elk-1 030304 developmental biology 0303 health sciences biology Chemistry Signal transducing adaptor protein General Medicine biology.organism_classification Rats 3. Good health Cell biology Barbiturates Tetradecanoylphorbol Acetate Signal transduction 030217 neurology & neurosurgery HeLa Cells Protein Binding |
| Zdroj: | Journal of Biochemistry. 149:331-336 |
| ISSN: | 0021-924X |
| DOI: | 10.1093/jb/mvq147 |
| Popis: | 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 (IC(50) 18 and 36 µM, respectively). BAS 02104951 also inhibited the interaction of PKCε with its adaptor protein receptor for activated C-kinase 2 (RACK2) (IC(50) 28.5 µM). BAS 02104951 also inhibited 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced Elk-1 phosphorylation in HeLa cells, translocation of PKCε 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. |
| Databáze: | OpenAIRE |
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