Extracellular signal-regulated kinase binds to TFII-I and regulates its activation of the c-fos promoter.
We have previously shown that TFII-I enhances transcriptional activation of the c-fos promoter through interactions with upstream elements in a signal-dependent manner. Here we demonstrate that activated Ras and RhoA synergize with TFII-I for c-fos promoter activation, whereas dominant-negative Ras and RhoA inhibit these effects of TFII-I. The Mek1 inhibitor, ... PD98059 abrogates the enhancement of the c-fos promoter by TFII-I, indicating that TFII-I function is dependent on an active mitogen-activated protein (MAP) kinase pathway. Analysis of the TFII-I protein sequence revealed that TFII-I contains a consensus MAP kinase interaction domain (D box). Consistent with this, we have found that TFII-I forms an in vivo complex with extracellular signal-related kinase (ERK). Point mutations within the consensus MAP kinase binding motif of TFII-I inhibit its ability to bind ERK and its ability to enhance the c-fos promoter. Therefore, the D box of TFII-I is required for its activity on the c-fos promoter. Moreover, the interaction between TFII-I and ERK can be regulated. Serum stimulation enhances complex formation between TFII-I and ERK, and dominant-negative Ras abrogates this interaction. In addition, TFII-I can be phosphorylated in vitro by ERK and mutation of consensus MAP kinase substrate sites at serines 627 and 633 impairs the phosphorylation of TFII-I by ERK and its activity on the c-fos promoter. These results suggest that ERK regulates the activity of TFII-I by direct phosphorylation.
Mesh Terms:
3T3 Cells, Amino Acid Sequence, Animals, Base Sequence, DNA Primers, DNA-Binding Proteins, Gene Expression Regulation, Genes, fos, Humans, Mice, Mitogen-Activated Protein Kinases, Molecular Sequence Data, Phosphorylation, Promoter Regions, Genetic, Recombinant Proteins, Sequence Homology, Amino Acid, Signal Transduction, Transcription Factors, ras Proteins, rho GTP-Binding Proteins
3T3 Cells, Amino Acid Sequence, Animals, Base Sequence, DNA Primers, DNA-Binding Proteins, Gene Expression Regulation, Genes, fos, Humans, Mice, Mitogen-Activated Protein Kinases, Molecular Sequence Data, Phosphorylation, Promoter Regions, Genetic, Recombinant Proteins, Sequence Homology, Amino Acid, Signal Transduction, Transcription Factors, ras Proteins, rho GTP-Binding Proteins
Mol. Cell. Biol.
Date: Feb. 01, 2000
PubMed ID: 10648599
View in: Pubmed Google Scholar
Download Curated Data For This Publication
10636
Switch View:
- Interactions 2