| Autor: |
Cha HC; Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI 48109-0622, USA., Oak NR, Kang S, Tran TA, Kobayashi S, Chiang SH, Tenen DG, MacDougald OA |
| Jazyk: |
angličtina |
| Zdroj: |
The Journal of biological chemistry [J Biol Chem] 2008 Jun 27; Vol. 283 (26), pp. 18002-11. Date of Electronic Publication: 2008 Apr 11. |
| DOI: |
10.1074/jbc.M800419200 |
| Abstrakt: |
The transcription factor CCAAT/enhancer-binding protein alpha (C/EBPalpha) is required during adipogenesis for development of insulin-stimulated glucose uptake. Modes for regulating this function of C/EBPalpha have yet to be determined. Phosphorylation of C/EBPalpha on Ser-21 has been implicated in the regulation of granulopoiesis and hepatic gene expression. To explore the role of Ser-21 phosphorylation on C/EBPalpha function during adipogenesis, we developed constructs in which Ser-21 was mutated to alanine (S21A) to model dephosphorylation. In two cell culture models deficient in endogenous C/EBPalpha, enforced expression of S21A-C/EBPalpha resulted in normal lipid accumulation and expression of many adipogenic markers. However, S21A-C/EBPalpha had impaired ability to activate the Glut4 promoter specifically, and S21A-C/EBPalpha expression resulted in diminished GLUT4 and adiponectin expression, as well as reduced insulin-stimulated glucose uptake. No defects in insulin signaling or GLUT4 vesicle trafficking were identified with S21A-C/EBPalpha expression, and when exogenous GLUT4 expression was enforced to normalize expression in S21A-C/EBPalpha cells, insulin-responsive glucose transport was reconstituted, suggesting that the primary defect was a deficit in GLUT4 levels. Mice in which endogenous C/EBPalpha was replaced with S21A-C/EBPalpha displayed reduced GLUT4 and adiponectin protein expression in epididymal adipose tissue and increased blood glucose compared with wild-type littermates. These results suggest that phosphorylation of C/EBPalpha on Ser-21 may regulate adipocyte gene expression and whole body glucose homeostasis. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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