ERK phosphorylation potentiates Elk‐1‐mediated ternary complex formation and transactivation.

H Gille, M Kortenjann, O Thomae, C Moomaw… - The EMBO …, 1995 - embopress.org
H Gille, M Kortenjann, O Thomae, C Moomaw, C Slaughter, MH Cobb, PE Shaw
The EMBO journal, 1995embopress.org
Induction of the human c‐fos proto‐oncogene by mitogens depends on the formation of a
ternary complex by p62TCF with the serum response factor (SRF) and the serum response
element (SRE). We demonstrate that Elk‐1, a protein closely related to p62TCF 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 …
Induction of the human c‐fos proto‐oncogene by mitogens depends on the formation of a ternary complex by p62TCF with the serum response factor (SRF) and the serum response element (SRE). We demonstrate that Elk‐1, a protein closely related to p62TCF 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.
embopress.org