Interaction of transcription factors with serum response factor. Identification of the Elk-1 binding surface

• Published in: The Journal of biological chemistry 1998-04, Vol.273 (17), p.10506-10514
• Main Authors: Ling, Y, West, A G, Roberts, E C, Lakey, J H, Sharrocks, A D
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; DNA - chemistry; DNA - metabolism; DNA-Binding Proteins - chemistry; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; ets-Domain Protein Elk-1; Molecular Sequence Data; Mutagenesis, Site-Directed; Nuclear Proteins - chemistry; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; Nucleic Acid Conformation; Protein Binding; Proto-Oncogene Proteins - metabolism; Serum Response Factor; Transcription Factors - metabolism
• ISSN: 0021-9258
• DOI: 10.1074/jbc.273.17.10506

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.