Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
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DNA-Binding Proteins / metabolism
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Gene Expression Regulation* / genetics
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Genes, fos / genetics*
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HeLa Cells
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Humans
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Immunohistochemistry
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JNK Mitogen-Activated Protein Kinases
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MAP Kinase Kinase Kinase 1*
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Mitogen-Activated Protein Kinase 1
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Mitogen-Activated Protein Kinase 3
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Mitogen-Activated Protein Kinase 9
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Mitogen-Activated Protein Kinases*
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Nuclear Proteins / metabolism
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Phosphorylation
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Protein Kinases / metabolism*
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Protein Serine-Threonine Kinases / metabolism
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Proto-Oncogene Proteins / metabolism*
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Serum Response Factor
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Transcription Factors / metabolism*
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Transcription, Genetic / genetics
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Transfection / genetics
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Ultraviolet Rays
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ets-Domain Protein Elk-1
Substances
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DNA-Binding Proteins
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ELK1 protein, human
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Nuclear Proteins
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Proto-Oncogene Proteins
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Serum Response Factor
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Transcription Factors
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ets-Domain Protein Elk-1
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Protein Kinases
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Mitogen-Activated Protein Kinase 9
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Protein Serine-Threonine Kinases
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Calcium-Calmodulin-Dependent Protein Kinases
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JNK Mitogen-Activated Protein Kinases
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Mitogen-Activated Protein Kinase 1
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Mitogen-Activated Protein Kinase 3
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Mitogen-Activated Protein Kinases
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MAP Kinase Kinase Kinase 1
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MAP3K1 protein, human