The SRF accessory protein Elk-1 contains a growth factor-regulated transcriptional activation domain.
The Elk-1 and SRF transcription factors form a ternary complex at the c-fos serum response element (SRE). Growth factor stimulation rapidly induces a reversible change in the electrophoretic mobility of the ternary complex, accompanied by increased phosphorylation of the Elk-1 C-terminal region and by the activation of a 42 kd cellular Elk-1 kinase. Phosphorylation of Elk-1 in vitro by partially purified p42/p44 MAP kinase induces a similar reduction in ternary complex mobility but has little effect on the efficiency of its formation. In vitro, MAP kinase phosphorylates the Elk-1 C-terminal region at multiple sites, which are also phosphorylated following growth factor stimulation in vivo. The Elk-1 C-terminal region functions as a regulated transcriptional activation domain whose activity in vivo is dependent on the integrity of the MAP kinase sites. These findings directly link transcriptional activation by the SRE to the growth factor-regulated phosphorylation of an SRE-binding protein.
Marais
R
R
Transcription Laboratory, Imperial Cancer Research Fund, London, England.
Wynne
J
J
Treisman
R
R
D016475:3T3 Cells; D000818:Animals; D001483:Base Sequence; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005260:Female; D006133:Growth Substances / Q000494:pharmacology*; D006367:HeLa Cells; D006801:Humans; D046911:Macromolecular Substances; D051379:Mice; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009687:Nuclear Proteins / Q000378:metabolism*; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins; D012045:Regulatory Sequences, Nucleic Acid; D015682:Retroviridae Proteins, Oncogenic / Q000235:genetics*; D017384:Sequence Deletion; D026362:Serum Response Factor; D014157:Transcription Factors / Q000378:metabolism*; D015533:Transcriptional Activation; D050807:ets-Domain Protein Elk-1
D004268:DNA-Binding Proteins; C494112:ELK1 protein, human; C494113:Elk1 protein, mouse; D006133:Growth Substances; D046911:Macromolecular Substances; D009687:Nuclear Proteins; D009838:Oligodeoxyribonucleotides; D010750:Phosphoproteins; D011518:Proto-Oncogene Proteins; D015682:Retroviridae Proteins, Oncogenic; D026362:Serum Response Factor; D014157:Transcription Factors; D050807:ets-Domain Protein Elk-1; D011494:Protein Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases