Distinct protein targets for signals acting at the c-fos serum response element.
The c-fos serum response element (SRE) is a primary nuclear target for intracellular signal transduction pathways triggered by growth factors. It is the target for both protein kinase C (PKC)-dependent and -independent signals. Function of the SRE requires binding of a cellular protein, termed serum response factor (SRF). A second protein, p62TCF, recognizes the SRE-SRF complex to form a ternary complex. A mutated SRE that bound SRF but failed to form the ternary complex selectively lost response to PKC activators, but retained response to PKC-independent signals. Thus, two different signaling pathways act through discrete nuclear targets at the SRE. At least one of these pathways functions by recruitment of a pathway-specific accessory factor (p62TCF). These results offer a molecular mechanism to account for the biological specificity of signals that appear to act through common DNA sequence elements.
Graham
R
R
Cold Spring Harbor Laboratory, NY 11724.
Gilman
M
M
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D001769:Blood; D002460:Cell Line; D004247:DNA / Q000378:metabolism; D004742:Enhancer Elements, Genetic; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009687:Nuclear Proteins / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D011493:Protein Kinase C / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016760:Proto-Oncogene Proteins c-fos; D015290:Second Messenger Systems; D026362:Serum Response Factor; D015398:Signal Transduction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014162:Transfection
D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D026362:Serum Response Factor; D004247:DNA; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate