Chromatin-bound mitogen-activated protein kinases transmit dynamic signals in transcription complexes in β-cells

Michael C. Lawrence, Kathleen McGlynn, Chunli Shao, Lingling Duan, Bashoo Naziruddin, Marlon F. Levy, Melanie H. Cobb

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

MAPK pathways regulate transcription through phosphorylation of transcription factors and other DNA-binding proteins. In pancreatic β-cells, ERK1/2 are required for transcription of the insulin gene and several other genes in response to glucose. We show that binding of glucose-sensitive transcription activators and repressors to the insulin gene promoter depends on ERK1/2 activity. We also find that glucose and NGF stimulate the binding of ERK1/2 to the insulin gene and other promoters. An ERK1/2 cascade module, including MEK1/2 and Rsk, are found in complexes bound to these promoters. These findings imply that MAPK-containing signaling complexes are positioned on sensitive promoters with their protein substrates to modulate transcription in situ in response to incoming signals.

Original languageEnglish (US)
Pages (from-to)13315-13320
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume105
Issue number36
DOIs
StatePublished - Sep 9 2008

Fingerprint

Mitogen-Activated Protein Kinases
Chromatin
Insulin
Glucose
Genes
DNA-Binding Proteins
Nerve Growth Factor
Transcription Factors
Phosphorylation
Proteins

Keywords

  • c-fos
  • C/EBP-β
  • ERK1/2
  • Hyperglycemia
  • Insulin gene transcription

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Chromatin-bound mitogen-activated protein kinases transmit dynamic signals in transcription complexes in β-cells. / Lawrence, Michael C.; McGlynn, Kathleen; Shao, Chunli; Duan, Lingling; Naziruddin, Bashoo; Levy, Marlon F.; Cobb, Melanie H.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 105, No. 36, 09.09.2008, p. 13315-13320.

Research output: Contribution to journalArticle

Lawrence, Michael C. ; McGlynn, Kathleen ; Shao, Chunli ; Duan, Lingling ; Naziruddin, Bashoo ; Levy, Marlon F. ; Cobb, Melanie H. / Chromatin-bound mitogen-activated protein kinases transmit dynamic signals in transcription complexes in β-cells. In: Proceedings of the National Academy of Sciences of the United States of America. 2008 ; Vol. 105, No. 36. pp. 13315-13320.
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