Ha-Ras functions downstream from protein kinase C in v-Fps-induced gene expression mediated by TPA response elements.
v-Fps activates promoters under the control of the 12-O-tetradecanoyl phorbol 13-acetate (TPA) response element (TRE). The induction of TRE-mediated transcription by v-Fps was sensitive to a dominant-negative mutant of Ha-Ras. An activated derivative of Ha-Ras, v-Ha-Ras, also activated TRE-mediated transcription. v-Fps-induced TRE-mediated gene expression was sensitive to depleting cells of protein kinase C (PKC), whereas v-Ha-Ras-induced TRE-mediated transcription was insensitive to PKC depletion, suggesting that Ha-Ras functions downstream from PKC in v-Fps-induced TRE-mediated gene expression. Consistent with this hypothesis, the induction of TRE-mediated gene expression by phorbol esters that activate PKC directly was blocked by the dominant-negative Ha-Ras mutant. Thus, v-Fps-induced activation of TRE-mediated gene expression is via an intracellular signaling mechanism that is dependent upon both PKC and Ha-Ras and Ha-Ras functions downstream from PKC.
Alexandropoulos
K
K
Institute for Biomolecular Structure and Function, Hunter College, City University of New York, New York 10021.
Qureshi
S A
SA
Foster
D A
DA
D016475:3T3 Cells; D000818:Animals; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D015681:Fusion Proteins, gag-onc / Q000494:pharmacology*; D019204:GTP-Binding Proteins / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects*; D011905:Genes, ras; D051379:Mice; D009154:Mutation; D011493:Protein Kinase C / Q000502:physiology*; D011505:Protein-Tyrosine Kinases; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D015681:Fusion Proteins, gag-onc; D015500:Chloramphenicol O-Acetyltransferase; D011505:Protein-Tyrosine Kinases; C068415:v-fps oncogene protein, Fujinami sarcoma virus; D011493:Protein Kinase C; D019204:GTP-Binding Proteins; D013755:Tetradecanoylphorbol Acetate