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PMID:7889942
| Citation |
Gille, H, Kortenjann, M, Thomae, O, Moomaw, C, Slaughter, C, Cobb, MH and Shaw, PE (1995) ERK phosphorylation potentiates Elk-1-mediated ternary complex formation and transactivation. EMBO J. 14:951-62 |
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| Abstract |
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. |
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| Keywords |
3T3 Cells; Amino Acid Sequence; Animals; Base Sequence; Calcium-Calmodulin-Dependent Protein Kinases/metabolism; DNA/metabolism; DNA-Binding Proteins/metabolism; DNA-Binding Proteins/physiology; Genes, fos/genetics; Humans; Mice; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; Mitogen-Activated Protein Kinases; Molecular Sequence Data; PC12 Cells; Peptide Mapping; Phosphorylation; Promoter Regions, Genetic/genetics; Proto-Oncogene Proteins/metabolism; Proto-Oncogene Proteins/physiology; Rats; Recombinant Fusion Proteins/metabolism; Sequence Alignment; Sequence Analysis; Transcription Factors; Transcriptional Activation/physiology; ets-Domain Protein Elk-1 |
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Significance
Annotations
| Gene product | Qualifier | GO ID | GO term name | Evidence Code | with/from | Aspect | Notes | Status |
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