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 language | English (US) |
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Pages (from-to) | 13315-13320 |
Number of pages | 6 |
Journal | Proceedings of the National Academy of Sciences of the United States of America |
Volume | 105 |
Issue number | 36 |
DOIs | |
State | Published - Sep 9 2008 |
Keywords
- C/EBP-β
- ERK1/2
- Hyperglycemia
- Insulin gene transcription
- c-fos
ASJC Scopus subject areas
- General