Sp1 phosphorylation by Erk 2 stimulates DNA binding

Biochem Biophys Res Commun. 1999 Jan 19;254(2):454-61. doi: 10.1006/bbrc.1998.9964.


EGF stimulates gene expression through a variety of signal transduction pathways that include the ras-Erk pathway. We have shown previously that EGF receptor activation stimulates gastrin gene expression through a GC-rich element called gERE. This element binds Sp1 family members and raises the possibility that the ras-Erk signal transduction cascade may target this novel EGF responsive element. Moreover, it is known that Erk 2 is capable of phosphorylating other mitogen-inducible transcription factors, e.g., Elk, Sap suggesting that Erk may also inducibly phosphorylate Sp1. To test this hypothesis directly using cotransfection experiments, we show that ras and Erk 2 activation indeed target the gERE element. The Mek 1 kinase inhibitor, PD98059, blocks 50% of EGF-inducible gastrin promoter activity. Pretreatment of the extracts with recombinant Erk2 stimulated Sp1 binding; whereas dephosphorylation reduced but did not eliminate Sp1 binding. Together, these studies demonstrate the novel finding that inducible binding of Sp1 is regulated by its state of phosphorylation. Further, gastrin promoter activation is mediated in part by the ras-Erk signaling cascade that targets Sp1.

Publication types

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

MeSH terms

  • Adenocarcinoma
  • Base Sequence
  • Binding Sites
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
  • Enzyme Inhibitors / pharmacology
  • Epidermal Growth Factor / pharmacology
  • Epidermal Growth Factor / physiology
  • Flavonoids / pharmacology*
  • Gastrins / genetics
  • Gene Expression Regulation, Neoplastic
  • Genes, ras
  • Humans
  • Mitogen-Activated Protein Kinase 1
  • Oligodeoxyribonucleotides
  • Phosphorylation
  • Promoter Regions, Genetic
  • Signal Transduction
  • Sp1 Transcription Factor / metabolism*
  • Stomach Neoplasms
  • Transcription Factors / metabolism
  • Tumor Cells, Cultured


  • Enzyme Inhibitors
  • Flavonoids
  • Gastrins
  • Oligodeoxyribonucleotides
  • Sp1 Transcription Factor
  • Transcription Factors
  • Epidermal Growth Factor
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Mitogen-Activated Protein Kinase 1
  • 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one