Regulation of insulin gene transcription by ERK1 and ERK2 in pancreatic β cells

Shih Khoo, Steven C. Griffen, Ying Xia, Richard J. Baer, Michael S. German, Melanie H. Cobb

Research output: Contribution to journalArticlepeer-review

133 Scopus citations


We show that the mitogen-activated protein kinases ERK1/2 are components of the mechanism by which glucose stimulates insulin gene expression. ERK1/2 activity is required for glucose-dependent transcription from both the full-length rat insulin I promoter and the glucose-sensitive isolated E2A3/4 promoter element in intact islets and β cell lines. Dominant negative ERK2 and MEK inhibitors suppress glucose stimulation of the rat insulin I promoter and the E2A3/4 element. Overexpression of ERK2 is sufficient to stimulate transcription from the E2A3/4 element. The glucose-induced response is dependent upon ERK1/2 phosphorylation of a subset of transcription factors that include Beta2 (also known as NeuroD1) and PDX-1. Phosphorylation increases their functional activity and results in a cumulative transactivation of the promoter. Thus, ERK1/2 act at multiple points to transduce a glucose signal to insulin gene transcription.

Original languageEnglish (US)
Pages (from-to)32969-32977
Number of pages9
JournalJournal of Biological Chemistry
Issue number35
StatePublished - Aug 29 2003

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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