12-Deoxyphorbol-13-O-phenylacetate-20-acetate is not protein kinase C-beta isozyme-selective in vivo
| Autor: | Fred J. Evans, W. J. Ryves, Philip C. Gordge, D K Ways, S C Kiley, Peter J. Parker, Andrée R. Olivier |
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| Rok vydání: | 1994 |
| Předmět: |
Cancer Research
Biology Isozyme 3T3 cells Mice In vivo Phorbol Esters medicine Tumor Cells Cultured Animals Humans Phosphorylation Protein kinase A Protein kinase C Protein Kinase C Proteins General Medicine 3T3 Cells Molecular biology In vitro Enzyme Activation Isoenzymes medicine.anatomical_structure Biochemistry Cell culture |
| Zdroj: | Carcinogenesis. 15(2) |
| ISSN: | 0143-3334 |
| Popis: | The phorbol ester, 12-deoxyphorbol-13-O-phenylacetate-20-acetate (DOPPA) has been shown to activate specifically the protein kinase C (PKC)-beta 1 isozyme in vitro (1). We have investigated the potential of DOPPA as a PKC-beta 1/2 isozyme-specific agonist in intact cells, employing U937 cells, which express beta 1/2, epsilon and zeta PKC and in Swiss 3T3 cells which lack PKC-beta 1/2 but express alpha, delta, epsilon and zeta PKC. Immunoblot analysis with isozyme-specific antibodies indicated that DOPPA can mediate the subcellular redistribution and down-modulation of all endogenous PKC isozymes (except PKC-zeta) in both U937 and Swiss 3T3 cells. Prolonged treatment (> 6 h) of cultures in down-modulation studies is complicated by the metabolism of DOPPA to 12-deoxyphorbol-13-phenylacetate (DOPP), a compound which activates all PKC isozymes tested in vitro (Ryves, W. J., et al. (1991) FEBS Lett., 288, 5-9). Nevertheless, because DOPPA induced rapid and dose-dependent phosphorylation of p80 in cells which do not express PCK-beta, p80 phosphorylation in Swiss 3T3 cells indicates that DOPPA can activate a non-beta PKC in vivo. The data suggest that DOPPA cannot be used as a PKC-beta-selective agonist in intact cell studies. |
| Databáze: | OpenAIRE |
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