Inhibition of 12-O-tetradecanoylphorbol-13-acetate induction of c-fos mRNA by the protein kinase A inhibitor N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinoline sulfonamide.
The tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) can induce expression of many immediate-early genes, such as c-fos and c-jun. In this study, TPA increased c-fos mRNA, cellular cyclic AMP, and protein kinase A (PKA) activity in the first 30 min with similar inductive time courses. Treatment of NIH 3T3 cells with N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinoline sulfonamide (H-89), a PKA specific inhibitor, suppressed TPA induction of PKA activity and c-fos mRNA in a concentration-dependent manner, but did not inhibit serum-induced transcription. H-89 did not inhibit TPA and serum induction of c-jun mRNA. H-89 interfered with TPA-stimulated serum-responsive element-binding activity in a concentration-dependent manner, but did not inhibit TPA-induced mitogen- activated protein kinase 1/2 activity or Elk-1 phosphorylation. TPA stimulation of a c-fos promoter reporter construct was inhibited by overexpression of the dominant negative regulatory protein of PKA. In deletion studies, the H-89 inhibitory element was found to be localized between -563 and -379 in the c-fos promoter region. These results suggest that H-89 will be very useful for investigating the molecular mechanism of TPA induction of c-fos.[1]References
- Inhibition of 12-O-tetradecanoylphorbol-13-acetate induction of c-fos mRNA by the protein kinase A inhibitor N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinoline sulfonamide. Huang, Y.T., Lin, J.K., Lee, M.T. Biochem. Pharmacol. (1999) [Pubmed]
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