Integration of growth factor signals at the c-fos serum response element.
A transcription factor ternary complex composed of serum response factor (SRF) and a second factor, ternary complex factor (TCF), mediates the response of the c-fos Serum Response Element to growth factors and mitogens. In NIH3T3 fibroblasts, TCF binding is required for transcriptional activation by the SRE in response to activation of the Ras-Raf-ERK pathway. We compared the properties of three members of the TCF family, Elk-1, SAP-1 and SAP-2 (ERP/NET). Although all the proteins contain sequences required for ternary complex formation with SRF, only Elk-1 and SAP-1 appear to interact with the c-fos SRE efficiently in vivo. Each TCF contains a C-terminal activation domain capable of transcriptional activation in response to activation of the Ras-Raf-ERK pathway, and this is dependent on the integrity of S/T-P motifs conserved between all the TCF family members. In contrast, activation of the SRE by whole serum and the mitogenic phospholipid LPA requires SRF binding alone. Constitutively activated members of the Rho subfamily of Ras-like GTPases are also capable of inducing activation of the SRE in the absence of TCF; unlike activated Ras itself, these proteins do not activate the TCFs in NIH3T3 cells. At the SRE, SRF- and TCF-linked signalling pathways act synergistically to potentiate transcription.
Price
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MA
Transcription Laboratory, Imperial Cancer Research Fund, London, U.K.
Hill
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Treisman
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D016475:3T3 Cells; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000378:metabolism*; D020558:GTP Phosphohydrolases / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism; D017930:Genes, Reporter; D016762:Genes, fos; D006133:Growth Substances / Q000494:pharmacology*; D051379:Mice; D008954:Models, Biological; D009687:Nuclear Proteins / Q000378:metabolism*; D015513:Oncogene Proteins; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D050783:Proto-Oncogene Proteins c-ets; D011994:Recombinant Proteins / Q000378:metabolism; D026362:Serum Response Factor; D015398:Signal Transduction; D014157:Transcription Factors / Q000096:biosynthesis / Q000378:metabolism*; D015533:Transcriptional Activation; D014162:Transfection; D050807:ets-Domain Protein Elk-1; D050808:ets-Domain Protein Elk-4
D004268:DNA-Binding Proteins; C494113:Elk1 protein, mouse; C086924:Elk3 protein, mouse; C494194:Elk4 protein, mouse; D006133:Growth Substances; D009687:Nuclear Proteins; D015513:Oncogene Proteins; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D011994:Recombinant Proteins; D026362:Serum Response Factor; D014157:Transcription Factors; D050807:ets-Domain Protein Elk-1; D050808:ets-Domain Protein Elk-4; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins