Functional analysis of a growth factor-responsive transcription factor complex

Cell. 1993 Apr 23;73(2):395-406. doi: 10.1016/0092-8674(93)90238-l.


Serum response factor (SRF) forms a ternary complex at the c-fos serum response element (SRE) with an accessory factor, Elk-1. We constructed altered-binding specificity derivatives of SRF and Elk-1 that form a ternary complex at a mutated, inactive SRE; like Elk-1, the Elk-1 variant only binds its target as part of a ternary complex with SRF. Simultaneous expression of these SRF and Elk-1 derivatives restores serum-regulated activity to the mutated SRE in transfected cells. Efficient transcriptional activation is dependent on the regulated phosphorylation of Elk-1 C-terminal MAP kinase sites and requires the C-terminal sequences of SRF as well as SRF sequences that mediate ternary complex formation. These experiments provide direct evidence that SRF and Elk-1 functionally cooperate in the ternary complex at the SRE to regulate transcription.

MeSH terms

  • 3T3 Cells
  • Amino Acid Sequence
  • Animals
  • Bacterial Proteins / chemistry
  • Bacterial Proteins / metabolism
  • Base Sequence
  • DNA Mutational Analysis
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / metabolism*
  • Gene Expression Regulation / drug effects*
  • Growth Substances / pharmacology*
  • Mice
  • Molecular Sequence Data
  • Nuclear Proteins / chemistry
  • Nuclear Proteins / metabolism*
  • Phosphoproteins / metabolism
  • Phosphorylation
  • Promoter Regions, Genetic
  • Proto-Oncogene Proteins*
  • Recombinant Fusion Proteins / metabolism
  • Retroviridae Proteins, Oncogenic / chemistry
  • Retroviridae Proteins, Oncogenic / metabolism*
  • Serine Endopeptidases*
  • Serum Response Factor
  • Structure-Activity Relationship
  • Transcription Factors*
  • Transcription, Genetic / drug effects*
  • ets-Domain Protein Elk-1


  • Bacterial Proteins
  • DNA-Binding Proteins
  • Elk1 protein, mouse
  • Growth Substances
  • LexA protein, Bacteria
  • Nuclear Proteins
  • Phosphoproteins
  • Proto-Oncogene Proteins
  • Recombinant Fusion Proteins
  • Retroviridae Proteins, Oncogenic
  • Serum Response Factor
  • Transcription Factors
  • ets-Domain Protein Elk-1
  • Serine Endopeptidases