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.