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.
Mesh Terms:
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
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
EMBO J.
Date: Dec. 01, 1995
PubMed ID: 8846788
View in: Pubmed Google Scholar
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