Back to Search
Start Over
P38 Mitogen-Activated Protein Kinase Is the Central Regulator of Cycli AMP-Dependent Transcription of the Brown Fat Uncoupling Protein 1 Gene.
- Source :
- Molecular & Cellular Biology; Apr2004, Vol. 24 Issue 7, p3057-3067, 11p, 7 Diagrams
- Publication Year :
- 2004
-
Abstract
- It is well established that catecholamine-stimulated thermogenesis in brown fat requires β-adrenergic elevations in cyclic AMP (cAMP) to increase expression of the uncoupling protein 1 (UCP1) gene. However, little is known about the downstream components of the signaling cascade or the relevant transcription factor targets thereof. Here we demonstrate that cAMP- and protein kinase A-dependent activation of p38 mitogen-activated protein kinase (MAPK) in brown adipocytes is an indispensable step in the transcription of the UCP1 gene in mice. By phosphorylating activating transcription factor 2 (ATF-2) and peroxisome proliferator-activated receptor gamma (PPARγ) coativator 1α (PGC-1α), members of two distinct nuclear factor families, p38 MAPK controls the expression of the UCP1 gene through their respective interactions with a cAMP response element and a PPAR response element that both reside within a critical enhancer motif of the UCP1 gene. Activation of ATF-2 by p38 MAPK additionally serves as the cAMP sensor that increases expression of the PGC-1α gene itself in brown adipose tissue. In conclusion, our findings illustrate that by orchestrating the activity of multiple transcription factors, p38 MAPK is a central mediator of the cAMP signaling mechanism of brown fat that promotes thermogenesis. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 02707306
- Volume :
- 24
- Issue :
- 7
- Database :
- Complementary Index
- Journal :
- Molecular & Cellular Biology
- Publication Type :
- Academic Journal
- Accession number :
- 12801422
- Full Text :
- https://doi.org/10.1128/MCB.24.7.3057-3067.2004