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

Research output: Contribution to journalArticle

543 Citations (Scopus)

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
StatePublished - Jan 1 1995
Externally publishedYes

Fingerprint

Serum Response Element
Phosphorylation
Transcriptional Activation
Chemical activation
Serum Response Factor
Phosphopeptides
Mitogens
Epidermal Growth Factor
Alanine
Serine
fos Genes
Intercellular Signaling Peptides and Proteins
Proteins
Peptide Mapping
Phosphotransferases
Mitogen-Activated Protein Kinase 3
Cells
Peptides
Mutation
In Vitro Techniques

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.

ERK phosphorylation potentiates Elk-1-mediated ternary complex formation and transactivation. / Gille, H.; Kortenjann, M.; Thomae, O.; Moomaw, C.; Slaughter, Clive A.; Cobb, M. H.; Shaw, P. E.

In: EMBO Journal, Vol. 14, No. 5, 01.01.1995, p. 951-962.

Research output: Contribution to journalArticle

Gille, H, Kortenjann, M, Thomae, O, Moomaw, C, Slaughter, CA, Cobb, MH & Shaw, PE 1995, 'ERK phosphorylation potentiates Elk-1-mediated ternary complex formation and transactivation', EMBO Journal, vol. 14, no. 5, pp. 951-962.
Gille H, Kortenjann M, Thomae O, Moomaw C, Slaughter CA, Cobb MH et al. ERK phosphorylation potentiates Elk-1-mediated ternary complex formation and transactivation. EMBO Journal. 1995 Jan 1;14(5):951-962.
Gille, H. ; Kortenjann, M. ; Thomae, O. ; Moomaw, C. ; Slaughter, Clive A. ; Cobb, M. H. ; Shaw, P. E. / ERK phosphorylation potentiates Elk-1-mediated ternary complex formation and transactivation. In: EMBO Journal. 1995 ; Vol. 14, No. 5. pp. 951-962.
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