Differential regulation of endogenous glucose-6-phosphatase and phosphoenolpyruvate carboxykinase gene expression by the forkhead transcription factor FKHR in H4IIE-hepatoma cells
- PMID: 11467835
- DOI: 10.1006/bbrc.2001.5261
Differential regulation of endogenous glucose-6-phosphatase and phosphoenolpyruvate carboxykinase gene expression by the forkhead transcription factor FKHR in H4IIE-hepatoma cells
Abstract
The insulin responsive H4IIEC3 rat hepatoma cell line (H4 cells) was used in order to determine the role of the transcription factor FKHR in the regulation of phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase). Both PEPCK and G6Pase contain putative FKHR binding sites in their promoter sequence. Using a retroviral expression system, we stably overexpressed FKHR in H4-cells. FKHR was phosphorylated in a PI 3-kinase- and Akt-dependent manner, and was translocated from the nucleus to the cytoplasm in response to insulin. Furthermore, overexpression of FKHR markedly increased the expression of the catalytic subunit of G6Pase (basal about 2.5-fold, dexamethasone/cAMP stimulated about fivefold, respectively). In contrast, both basal and dexamethasone/cAMP-induced levels of PEPCK mRNA were unaffected by FKHR-overexpression. These data suggest a specific function for FKHR in the regulation of hepatic gluconeogenesis at the level of G6Pase, but not PEPCK gene expression.
Copyright 2001 Academic Press.
Similar articles
-
Regulation of glucose-6-phosphatase gene expression by protein kinase Balpha and the forkhead transcription factor FKHR. Evidence for insulin response unit-dependent and -independent effects of insulin on promoter activity.J Biol Chem. 2000 Nov 17;275(46):36324-33. doi: 10.1074/jbc.M003616200. J Biol Chem. 2000. PMID: 10960473
-
DYRK1 is a co-activator of FKHR (FOXO1a)-dependent glucose-6-phosphatase gene expression.Biochem Biophys Res Commun. 2003 Jan 17;300(3):764-9. doi: 10.1016/s0006-291x(02)02914-5. Biochem Biophys Res Commun. 2003. PMID: 12507516
-
Inhibition of GSK-3 selectively reduces glucose-6-phosphatase and phosphatase and phosphoenolypyruvate carboxykinase gene expression.Diabetes. 2001 May;50(5):937-46. doi: 10.2337/diabetes.50.5.937. Diabetes. 2001. PMID: 11334436
-
Insulin-regulated gene expression.Biochem Soc Trans. 2001 Aug;29(Pt 4):552-8. doi: 10.1042/bst0290552. Biochem Soc Trans. 2001. PMID: 11498027 Review.
-
Insulin regulation of PEPCK gene expression: a model for rapid and reversible modulation.Curr Drug Targets Immune Endocr Metabol Disord. 2005 Dec;5(4):423-37. doi: 10.2174/156800805774912962. Curr Drug Targets Immune Endocr Metabol Disord. 2005. PMID: 16375695 Review.
Cited by
-
Analysis of hepatic gene transcription in mice expressing insulin-insensitive GSK3.Biochem J. 2005 Dec 15;392(Pt 3):633-9. doi: 10.1042/BJ20051046. Biochem J. 2005. PMID: 16176184 Free PMC article.
-
Insulin activates RSK (p90 ribosomal S6 kinase) to trigger a new negative feedback loop that regulates insulin signaling for glucose metabolism.J Biol Chem. 2013 Oct 25;288(43):31165-76. doi: 10.1074/jbc.M113.474148. Epub 2013 Sep 13. J Biol Chem. 2013. PMID: 24036112 Free PMC article.
-
STAT3 targets the regulatory regions of gluconeogenic genes in vivo.Mol Endocrinol. 2009 Jun;23(6):827-37. doi: 10.1210/me.2008-0264. Epub 2009 Mar 5. Mol Endocrinol. 2009. PMID: 19264844 Free PMC article.
-
Expression of liver cancer associated gene HCCA3.World J Gastroenterol. 2001 Dec;7(6):821-5. doi: 10.3748/wjg.v7.i6.821. World J Gastroenterol. 2001. PMID: 11854909 Free PMC article.
-
FoxO1 regulates muscle fiber-type specification and inhibits calcineurin signaling during C2C12 myoblast differentiation.Mol Cell Biochem. 2011 Feb;348(1-2):77-87. doi: 10.1007/s11010-010-0640-1. Epub 2010 Nov 16. Mol Cell Biochem. 2011. PMID: 21080037
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Research Materials
Miscellaneous
