Induction of c-fos expression through JNK-mediated TCF/Elk-1 phosphorylation

EMBO J. 1995 Dec 1;14(23):5957-64.

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

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
  • DNA-Binding Proteins / metabolism
  • Gene Expression Regulation* / genetics
  • Genes, fos / genetics*
  • 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 / metabolism
  • Phosphorylation
  • Protein Kinases / metabolism*
  • Protein-Serine-Threonine Kinases / metabolism
  • Proto-Oncogene Proteins / metabolism*
  • Serum Response Factor
  • Transcription Factors / metabolism*
  • Transcription, Genetic / genetics
  • Transfection / genetics
  • Ultraviolet Rays
  • ets-Domain Protein Elk-1

Substances

  • DNA-Binding Proteins
  • ELK1 protein, human
  • Nuclear Proteins
  • Proto-Oncogene Proteins
  • Serum Response Factor
  • Transcription Factors
  • ets-Domain Protein Elk-1
  • Protein Kinases
  • Mitogen-Activated Protein Kinase 9
  • Protein-Serine-Threonine Kinases
  • Calcium-Calmodulin-Dependent Protein Kinases
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinases
  • MAP Kinase Kinase Kinase 1
  • MAP3K1 protein, human