ERK phosphorylation potentiates Elk-1-mediated ternary complex formation and transactivation

H. Gille, M. Kortenjann, O. Thomae, C. Moomaw, Clive A. Slaughter, M. H. Cobb, P. E. Shaw

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550 Scopus citations

Abstract

Induction of the human c-fos proto-oncogene by mitogens depends on the formation of a ternary complex by p62(TCF) with the serum response factor (SRF) and the serum response element (SRE). We demonstrate that Elk-1, a protein closely related to p62(TCF) in function, is a nuclear target of two members of the MAP kinase family, ERK1 and ERK2. Phosphorylation of Elk-1 increases the yield of ternary complex in vitro. At least five residues in the C-terminal domain of Elk-1 are phosphorylated upon growth factor stimulation of NIH3T3 cells. These residues are also phosphorylated by purified ERK1 in vitro, as determined by a combination of phosphopeptide sequencing and 2-D peptide mapping. Conversion of two of these phospho-acceptor sites to alanine impairs the formation of ternary complexes by the resulting Elk-1 proteins. Removal of these serine residues also drastically diminishes activation of the c-fos promoter in epidermal growth factor-treated cells, Analogous mutations at other sites impair activation to a lesser extent without affecting ternary complex formation in vitro. Our results indicate that phosphorylation regulates ternary complex formation by Elk-1, which is a prerequisite for the manifestation of its transactivation potential at the c-fos SRE.

Original languageEnglish (US)
Pages (from-to)951-962
Number of pages12
JournalEMBO Journal
Volume14
Issue number5
Publication statusPublished - Jan 1 1995
Externally publishedYes

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Keywords

  • ERK
  • Elk-1
  • Phosphorylation
  • c-fos
  • p62(TCF)

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Cite this

Gille, H., Kortenjann, M., Thomae, O., Moomaw, C., Slaughter, C. A., Cobb, M. H., & Shaw, P. E. (1995). ERK phosphorylation potentiates Elk-1-mediated ternary complex formation and transactivation. EMBO Journal, 14(5), 951-962.