Activation of the c-fos gene by UV and phorbol ester: different signal transduction pathways converge to the same enhancer element.
In NIH3T3 cells stably transfected with the human c-fos gene, serum, platelet derived growth factor (PDGF), phorbol ester (12-O-tetradecanoyl-phorbol-13-acetate, TPA), ultraviolet irradiation (UV) and 3'-5'-cyclic adenosine monophosphate (cAMP) cause a transient and rapid activation of both the endogenous and the transfected c-fos genes. While serum, TPA, UV and PDGF dependent activation of the gene is severely impaired, when the serum responsive element from position -319 to -300 (SRE, Treisman, 1985) is destroyed, a full response to cAMP is retained. Insertion of a synthetic oligonucleotide corresponding to the SRE element upstream of position -96 restores the responses to TPA and serum, and large parts of the responses to UV and PDGF. The signal transduction chains elicited by UV and TPA are blocked by an inhibitor of protein kinase. Only TPA, however, causes the translocation of protein kinase C to the membrane. UV and TPA treated cells become refractory to a second stimulation by the same agent at 3 or 24 hours after the first treatment. Alternating the agents, however, leads to full responses. In addition, saturating doses of UV and TPA are at least additive. Ca-ionophores severely reduce only UV induced c-fos expression. These data indicate, that different signal transduction pathways elicited by growth promoting agents and by UV induced stress converge onto the same enhancer element.
Büscher
M
M
Kernforschungszentrum Karlsruhe, Institut für Genetik und Toxikologie, Federal Republic of Germany.
Rahmsdorf
H J
HJ
Litfin
M
M
Karin
M
M
Herrlich
P
P
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000818:Animals; D001790:Blood Physiological Phenomena; D002118:Calcium / Q000378:metabolism; D003470:Culture Media / Q000494:pharmacology; D000242:Cyclic AMP / Q000494:pharmacology; D004742:Enhancer Elements, Genetic; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology; D051379:Mice; D009857:Oncogenes / Q000187:drug effects / Q000528:radiation effects; D010879:Piperazines / Q000494:pharmacology; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics*; D016760:Proto-Oncogene Proteins c-fos; D015398:Signal Transduction / Q000187:drug effects / Q000528:radiation effects; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014466:Ultraviolet Rays
D003470:Culture Media; D007546:Isoquinolines; D010879:Piperazines; D010982:Platelet-Derived Growth Factor; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000242:Cyclic AMP; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium