Dual role for mitogen-activated protein kinase (Erk) in insulin-dependent regulation of Fra-1 (fos-related antigen-1) transcription and phosphorylation

Toby W Hurd, Ainsley A Culbert, Kenneth J Webster, Jeremy M Tavaré

Research output: Contribution to journalArticlepeer-review


Insulin regulates the activity of the AP-1 (activator protein-1) transcriptional complex in several cell types. One component of the AP-1 complex is the transcription factor Fra-1 (fos-related antigen-1), and we have demonstrated previously that insulin stimulates the expression of Fra-1 mRNA in CHO.T cells [Griffiths, Black, Culbert, Dickens, Shaw, Gillespie and Tavaré (1998) Biochem. J. 335, 19-26]. Here we demonstrate that insulin stimulates the activity of a fra-1 promoter linked to a luciferase reporter gene, indicating that the ability of insulin to induce expression of Fra-1 mRNA is due, at least in part, to an increase in gene transcription. Furthermore, we found that insulin induces the serine phosphorylation of Fra-1 and reduces its mobility during SDS/PAGE as a result of phosphorylation. The ability of insulin to induce the accumulation of Fra-1 mRNA, stimulate the fra-1 promoter and stimulate phosphorylation of Fra-1 all require the mitogen-activated protein (MAP) kinase cascade, which leads to the activation of extracellular-signal-regulated kinase (Erk) 1/2. Consequently, our results demonstrate that the Erk cascade plays a dual role in the co-ordinated regulation of the transcription and the phosphorylation of Fra-1 by insulin.

Original languageEnglish
Pages (from-to)573-80
Number of pages8
JournalBiochemical Journal
Issue numberPt 2
Publication statusPublished - 1 Dec 2002


  • 3T3 Cells
  • Adenoviridae
  • Animals
  • Base Sequence
  • Butadienes
  • CHO Cells
  • Cricetinae
  • Doxycycline
  • Electrophoresis, Polyacrylamide Gel
  • Enzyme Inhibitors
  • Genetic Vectors
  • Insulin
  • MAP Kinase Kinase Kinase 1
  • Mice
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinases
  • Molecular Sequence Data
  • Mutation
  • Nitriles
  • Phosphorylation
  • Promoter Regions, Genetic
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-fos
  • Recombinant Proteins
  • Transcription, Genetic


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