INTERACTION OF TRANSCRIPTION FACTORS WITH SERUM RESPONSE FACTOR - IDENTIFICATION OF THE ELK-1 BINDING SURFACE

Serum response elements (SREs) play important roles in transforming ex tracellular signals into specific nuclear responses. The SRE-binding p rotein, serum response factor (SRF), plays a pivotal role in this proc ess. Several transcription factors have been shown to interact with SR F and thereby create distinct complexes with different regulatory pote ntials, The ETS domain transcription factor Elk-1 is one such protein and serves to integrate distinct mitogen activated protein kinase casc ades at SREs, Elk-l uses a short hydrophobic surface presented on the surface of an ct-helix to interact with SRF, In this study we have use d site-directed mutagenesis to identify residues in SRF that comprise the Elk-l binding surface. The Elk-1 binding surface is composed of re sidues 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 fact or Fli-1, indicating that although some overlap with the Elk-1 binding surface occurs, their interaction surfaces on SRF are distinct. Our d ata 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.