EGF stimulates gastrin promoter through activation of Sp1 kinase activity

Sergey Chupreta, Ming Du, Andrea Todisco, Juanita L. Merchant

Research output: Contribution to journalArticlepeer-review

64 Scopus citations


Epidermal growth factor (EGF) receptor activation stimulates gastrin gene expression through a GC-rich element called gastrin EGF response element (gERE). This element is bound by Sp1 family members and is a target of the ras-extracellular signal-regulated kinase (Erk) signal transduction cascade. This raised the possibility that Sp1 may be phosphorylated by kinases of this signaling pathway. Erk is capable of phosphorylating other mitogen-inducible transcription factors, e.g., Elk and Sap, suggesting that Erk may also mediate EGF-dependent phosphorylation of Sp1. This possibility was tested by studying Sp1-dependent kinase activity in extracts prepared from EGF- activated AGS cells by use of solid-phase kinase assays and immunoprecipitation of metabolically labeled Sp1. The results revealed that Sp1 kinase activity (like gastrin promoter activation) is inhibited by PD- 98059 and, therefore, is dependent on mitogen-activated protein kinase kinase 1 (Mek 1). However, EGF-dependent activation of endogenous Erk did not account for most of the Sp1 kinase activity, since Erk and additional Sp1 kinase activity analyzed in a solid-phase kinase assay eluted from an ion- exchange column in different fractions. Phosphoamino acid analysis of in vivo radiolabeled Sp1 demonstrated that the kinase phosphorylates Sp1 on Ser and Thr in response to EGF. Therefore, most EGF-stimulated Sp1 kinase activity is Mek 1 dependent and distinct from Erk.

Original languageEnglish (US)
Pages (from-to)C697-C708
JournalAmerican Journal of Physiology - Cell Physiology
Issue number4 47-4
StatePublished - 2000
Externally publishedYes


  • Epidermal growth factor
  • Extracellular signal-regulated kinase
  • Gene expression
  • PD-98059
  • Phosphorylation
  • Signal transduction

ASJC Scopus subject areas

  • Physiology
  • Cell Biology


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