Induction of c-fos expression through JNK-mediated TCF/Elk-1 phosphorylation.
Growth factors induce c-fos transcription by stimulating phosphorylation of transcription factor TCF/Elk-1, which binds to the serum response element (SRE). Under such conditions Elk-1 could be phosphorylated by the mitogen-activated protein kinases (MAPKs) ERK1 and ERK2. However, c-fos transcription and SRE activity are also induced by stimuli, such as UV irradiation and activation of the protein kinase MEKK1, that cause only an insignificant increase in ERK1/2 activity. However, both of these stimuli strongly activate two other MAPKs, JNK1 and JNK2, and stimulate Elk-1 transcriptional activity and phosphorylation. We find that the JNKs are the predominant Elk-1 activation domain kinases in extracts of UV-irradiated cells and that immunopurified JNK1/2 phosphorylate Elk-1 on the same major sites recognized by ERK1/2, that potentiate its transcriptional activity. Finally, we show that UV irradiation, but not serum or phorbol esters, stimulate translocation of JNK1 to the nucleus. As Elk-1 is most likely phosphorylated while bound to the c-fos promoter, these results suggest that UV irradiation and MEKK1 activation stimulate TCF/Elk-1 activity through JNK activation, while growth factors induce c-fos through ERK activation.
Pubmed ID: 8846788 RIS Download
Calcium-Calmodulin-Dependent Protein Kinases | DNA-Binding Proteins | Gene Expression Regulation | Genes, fos | HeLa Cells | Humans | Immunohistochemistry | JNK Mitogen-Activated Protein Kinases | MAP Kinase Kinase Kinase 1 | Mitogen-Activated Protein Kinase 1 | Mitogen-Activated Protein Kinase 3 | Mitogen-Activated Protein Kinase 9 | Mitogen-Activated Protein Kinases | Nuclear Proteins | Phosphorylation | Protein Kinases | Protein-Serine-Threonine Kinases | Proto-Oncogene Proteins | Serum Response Factor | Transcription Factors | Transcription, Genetic | Transfection | Ultraviolet Rays | ets-Domain Protein Elk-1