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 journalArticle

118 Citations (Scopus)

Abstract

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
Volume278
Issue number35
DOIs
StatePublished - Aug 29 2003

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Transcription
Genes
Insulin
Glucose
Phosphorylation
Rats
Mitogen-Activated Protein Kinase 1
Mitogen-Activated Protein Kinase Kinases
Mitogen-Activated Protein Kinases
Islets of Langerhans
Gene expression
Transcriptional Activation
Transcription Factors
Cells
Gene Expression
Cell Line

ASJC Scopus subject areas

  • Biochemistry

Cite this

Regulation of insulin gene transcription by ERK1 and ERK2 in pancreatic β cells. / Khoo, Shih; Griffen, Steven C.; Xia, Ying; Baer, Richard J.; German, Michael S.; Cobb, Melanie H.

In: Journal of Biological Chemistry, Vol. 278, No. 35, 29.08.2003, p. 32969-32977.

Research output: Contribution to journalArticle

Khoo, Shih ; Griffen, Steven C. ; Xia, Ying ; Baer, Richard J. ; German, Michael S. ; Cobb, Melanie H. / Regulation of insulin gene transcription by ERK1 and ERK2 in pancreatic β cells. In: Journal of Biological Chemistry. 2003 ; Vol. 278, No. 35. pp. 32969-32977.
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