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†, and
- Melanie H. Cobb*,‡
- *Department of Pharmacology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390; and
- †The cGMP Islet Cell Processing Laboratory, Islet Cell Transplant Program, Baylor University Medical Center, Dallas, TX 75246
-
Contributed by Melanie H. Cobb, July 8, 2008 (received for review June 13, 2008)
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.
Footnotes
- ‡To whom correspondence should be addressed. E-mail: melanie.cobb{at}utsouthwestern.edu
-
Author contributions: M.C.L. and M.H.C. designed research; M.C.L., K.M., C.S., and L.D. performed research; B.N. and M.F.L. contributed new reagents/analytic tools; M.C.L. analyzed data; and M.C.L. and M.H.C. wrote the paper.
-
The authors declare no conflict of interest.
-
This article is a PNAS Direct Submission.
- © 2008 by The National Academy of Sciences of the USA
