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ERK PHOSPHORYLATION POTENTIATES ELK-1-MEDIATED TERNARY COMPLEX-FORMATION AND TRANSACTIVATION
Author(s): GILLE H, KORTENJANN M, THOMAE O, MOOMAW C, SLAUGHTER C, COBB MH, SHAW PE
Source: EMBO JOURNAL    Volume: 14    Issue: 5    Pages: 951-962    Published: MAR 1 1995  
Times Cited: 447     References: 46     
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.
Document Type: Article
Language: English
Addresses:
1. MAX PLANCK INST IMMUNBIOL, SPEMANN LABS, D-79108 FREIBURG, GERMANY
2. UNIV TEXAS, SW MED CTR, HOWARD HUGHES MED INST, DALLAS, TX 75235 USA
3. UNIV TEXAS, SW MED CTR, DEPT PHARMACOL, DALLAS, TX 75235 USA
Publisher: OXFORD UNIV PRESS UNITED KINGDOM, WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP
Subject Category: Biochemistry & Molecular Biology; Cell Biology
IDS Number: QM733
ISSN: 0261-4189
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