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 journalArticlepeer-review

52 Scopus citations

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

Keywords

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

ASJC Scopus subject areas

  • General

Fingerprint Dive into the research topics of 'Chromatin-bound mitogen-activated protein kinases transmit dynamic signals in transcription complexes in β-cells'. Together they form a unique fingerprint.

Cite this