Abstract
Serum response elements (SREs) play important roles in transforming extracellular signals into specific nuclear responses. The SRE-binding protein, serum response factor (SRF), plays a pivotal role in this process. Several transcription factors have been shown to interact with SRF and thereby create distinct complexes with different regulatory potentials. The ETS domain transcription factor Elk-1 is one such protein and serves to integrate distinct mitogen-activated protein kinase cascades at SREs. Elk-1 uses a short hydrophobic surface presented on the surface of an alpha-helix to interact with SRF. In this study we have used site-directed mutagenesis to identify residues in SRF that comprise the Elk-1 binding surface. The Elk-1 binding surface is composed of residues that lie on a hydrophobic surface-exposed groove located at the junction of the MADS box and C-terminal SAM motif. Different residues are implicated in interactions between SRF and the transcription factor Fli-1, indicating that although some overlap with the Elk-1 binding surface occurs, their interaction surfaces on SRF are distinct. Our data are consistent with the hypothesis that the SRF DNA-binding domain acts as docking site for multiple transcription factors that can bind to small surface-exposed patches within this domain.
Highlights
Serum response elements (SREs) play important roles in transforming extracellular signals into specific nuclear responses
Amino acids were either changed to alanines or to charged residues. The latter approach relies on introducing amino acids that will disrupt protein-protein contacts and the residues need not be in direct contact with Elk-1 but might instead be in very close proximity to residues comprising the binding surface
Moderate effects by introduction of charged residues suggest that the residues are close to the Elk-1binding motif, whereas severe effects indicate that the residues are probably within the binding surface
Summary
Serum response elements (SREs) play important roles in transforming extracellular signals into specific nuclear responses. The ETS domain transcription factor Elk-1 is one such protein and serves to integrate distinct mitogen-activated protein kinase cascades at SREs. Elk-1 uses a short hydrophobic surface presented on the surface of an ␣-helix to interact with SRF. The TCF-dependent pathways have been extensively studied In this complex, the TCF component is the recipient of signals transduced through the mitogen-activated protein kinase cascades A higher order complex involving SRF, Phox, and TFII-I/SPIN and the c-fos SRE has been identified [26] These diverse transcription factors show little homology with the Elk-1 B box, implying that they use alternative interaction motifs and different surfaces on SRF. Taken together our data are consistent with a model in which the SRF DNA-binding domain acts as a docking site with interaction surfaces for multiple transcription factors involved in diverse cellular processes
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
