c-fos transcriptional activation by IL-2 in mouse CTL-L2 cells is mediated through two distinct signal transduction pathways converging on the same enhancer element.
The c-fos protooncogene is suspected to play a major role during the activation of cells from different lineages. In particular, c-fos transcription is induced upon entry into a proliferation cycle in a wide variety of cell types. In this study, we have transfected an IL-2-dependent murine T cell line with chloramphenicol acetyl transferase (CAT) reporter constructs, harboring various regions of the human c-fos promoter. We show that IL-2 induces activation of fos CAT reporter constructs in these cells. Furthermore, the induction by IL-2 is mediated through a dyad symmetry element, the serum response element, which is also responsible for fos CAT reporter constructs activation by PMA, a pharmacologic activator of the protein kinase C (PKC). To assess any involvement of PKC in signal transduction for fos CAT reporter activation by IL-2, CTL-L2 cells were PKC-depleted by treatment with high doses of PMA. Such a treatment abolished the transcriptional response of fos CAT reporter constructs to PMA. In contrast, IL-2 was still able to activate fos CAT transcription, albeit with a lower efficiency. These results suggest that PMA-sensitive PKC might be part of intracellular transduction pathways leading to c-fos transcriptional activation by IL-2, and that at least one alternate pathway participates in the complete response. However, these distinct signal transduction pathways have the same DNA target on c-fos promoter, the serum response element.
Trouche
D
D
Laboratoire d'Immunobiologie Cellulaire, PR1 Institut Gustave Roussy, URA 11 56 CNRS, Villejuif, France.
Robin
P
P
Robillard
O
O
Sassone-Corsi
P
P
Harel-Bellan
A
A
D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D004742:Enhancer Elements, Genetic; D007376:Interleukin-2 / Q000494:pharmacology*; D051379:Mice; D008969:Molecular Sequence Data; D011493:Protein Kinase C / Q000502:physiology; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics*; D011519:Proto-Oncogenes; D012333:RNA, Messenger / Q000032:analysis; D015398:Signal Transduction; D013602:T-Lymphocytes, Cytotoxic / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects*
D007376:Interleukin-2; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D015500:Chloramphenicol O-Acetyltransferase; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate