0000000000470735
AUTHOR
Beate Richter
showing 3 related works from this author
Control of the mutagenicity of aromatic amines by protein kinases and phosphatases
1997
The role of protein kinase C and protein phosphatases was examined in the control of mutagenic metabolites of aromatic amines. Various metabolic activating systems derived from rat liver were treated with: 12-O-tetradecanoylphorbol-13-acetate (TPA), a protein kinase C modulator; okadaic acid (OA), a potent inhibitor of serine/threonine protein phosphatases (PP1 and PP2A); and ortho-vanadate (OV), an inhibitor of tyrosine phosphatases. TPA used over a wide concentration range (10−9–10−6 M) did not affect the bacterial mutagenicity of the aromatic amines and of the aromatic amide investigated, 2-aminoanthracene, 2-aminofluorene and 2-acetylaminofluorene (2AAF). At the molecular level, TPA did…
Differential modulation of CYP2E1 activity by cAMP-dependent protein kinase upon Ser129 replacement.
1998
Many toxic compounds are activated by cytochrome P450 (CYP) 2E1 to reactive metabolites, which represents a potential hazard for cellular homeostasis. Therefore knowledge about CYP2E1 regulation could be of great biological importance. It has been shown that CYP2E1 is controlled transcriptionally and post-translationally by phosphorylation. In the present study we investigated the role of serine-129 (Ser129) in the protein kinase A (PKA) recognition sequence motif Arg-Arg-Phe-Ser129. To gain further insights into the possible relevance of Ser129 for CYP2E1 function, Ser129 was replaced by alanine (Ala) or glycine (Gly) by site-directed mutations of the cDNA coding for CYP2E1. The mutant cDN…
Significance of Posttranslational Modification of Drug Metabolizing Enzymes by Phosphorylation for the Control of Carcinogenic Metabolites
1995
The total activity of foreign compound metabolizing enzymes may change by altering the amount or the specific activity of the enzyme by induction or repression, or by activation or inhibition. The important contribution of enzyme induction is well known (Conney 1982, Oesch 1986, Nebert and Jones 1989). This is a relatively slow process which requires the biosynthesis of the enzyme protein. The possibility of a faster regulation of foreign compound metabolism by posttranslational modification by phosphorylation of an already preexisting protein molecule has only recently received attention. A central role in the metabolism of foreign compounds is played by the cytochrome P450-dependent monoo…