Insulin stimulation of SREBP-1c processing in transgenic rat hepatocytes requires p70 S6-kinase

Proceedings of the National Academy of Sciences of the United States of America

Volumn 109, Issue 40, 2012, Pages 16184-16189

  Owen, Joshua L ^a   Zhang, Yuanyuan ^a   Bae, Soo Han ^a,b   Farooqi, Midhat S ^a   Liang, Guosheng ^a   Hammer, Robert E ^a   Goldstein, Joseph L ^a   Brown, Michael S ^a  

^a UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER   (United States)

^b Ewha Womans University   (South Korea)

Author keywords

Lipid metabolism; mTORC1 kinase

Indexed keywords

APOLIPOPROTEIN E; GLUCAGON; INSULIN; LIPID; MAMMALIAN TARGET OF RAPAMYCIN COMPLEX 1; MESSENGER RNA; PROTEIN KINASE INHIBITOR; PROTEIN P70; S6 KINASE; STEROL REGULATORY ELEMENT BINDING PROTEIN 1C;

ANIMAL CELL; ARTICLE; CELL ISOLATION; INSULIN METABOLISM; LIPOGENESIS; LIVER CELL; MALE; MOLECULAR DYNAMICS; NONHUMAN; PRIORITY JOURNAL; PROMOTER REGION; PROTEIN DEGRADATION; PROTEIN INDUCTION; PROTEIN PROCESSING; RAT; SIGNAL TRANSDUCTION; TRANSGENIC RAT;

ANIMALS; APOLIPOPROTEINS E; DNA PRIMERS; GENE TRANSFER TECHNIQUES; GLUCAGON; HUMANS; IMMUNOBLOTTING; INSULIN; LIPOGENESIS; LIVER; PROTEINS; RATS; RATS, SPRAGUE-DAWLEY; RATS, TRANSGENIC; REAL-TIME POLYMERASE CHAIN REACTION; RIBOSOMAL PROTEIN S6 KINASES, 70-KDA; STEROL REGULATORY ELEMENT BINDING PROTEIN 1;

RATTUS;

EID: 84867067610     PISSN: 00278424     EISSN: 10916490     Source Type: Journal    
DOI: 10.1073/pnas.1213343109     Document Type: Article

References (23)

1. Browning JD, Horton JD (2004) Molecular mediators of hepatic steatosis and liver injury. J Clin Invest 114:147-152. (Pubitemid 39071617)
2. Leavens KF, Birnbaum MJ (2011) Insulin signaling to hepatic lipid metabolism in health and disease. Crit Rev Biochem Mol Biol 46:200-215.
3. Horton JD, Goldstein JL, Brown MS (2002) SREBPs: Activators of the complete program of cholesterol and fatty acid synthesis in the liver. J Clin Invest 109:1125-1131. (Pubitemid 34496588)
4. Krycer JR, Sharpe LJ, Luu W, Brown AJ (2010) The Akt-SREBP nexus: Cell signaling meets lipid metabolism. Trends Endocrinol Metab 21:268-276.
5. Foretz M, Guichard C, Ferré P, Foufelle F (1999) Sterol regulatory element binding protein-1c is a major mediator of insulin action on the hepatic expression of glucokinase and lipogenesis-related genes. Proc Natl Acad Sci USA 96:12737-12742. (Pubitemid 29513572)
6. Shimomura I, et al. (1999) Insulin selectively increases SREBP-1c mRNA in the livers of rats with streptozotocin-induced diabetes. Proc Natl Acad Sci USA 96:13656-13661.
7. Shimomura I, et al. (2000) Decreased IRS-2 and increased SREBP-1c lead to mixed insulin resistance and sensitivity in livers of lipodystrophic and ob/ob mice. Mol Cell 6:77-86.
8. Chen G, Liang G, Ou J, Goldstein JL, Brown MS (2004) Central role for liver X receptor in insulin-mediated activation of Srebp-1c transcription and stimulation of fatty acid synthesis in liver. Proc Natl Acad Sci USA 101:11245-11250. (Pubitemid 39038332)
9. Hegarty BD, et al. (2005) Distinct roles of insulin and liver X receptor in the induction and cleavage of sterol regulatory element-binding protein-1c. Proc Natl Acad Sci USA 102:791-796. (Pubitemid 40282744)
10. Yellaturu CR, et al. (2005) Posttranslational processing of SREBP-1 in rat hepatocytes is regulated by insulin and cAMP. Biochem Biophys Res Commun 332:174-180. (Pubitemid 40719470)
11. Li S, Brown MS, Goldstein JL (2010) Bifurcation of insulin signaling pathway in rat liver: mTORC1 required for stimulation of lipogenesis, but not inhibition of gluconeogenesis. Proc Natl Acad Sci USA 107:3441-3446.
12. Brown MS, Goldstein JL (1997) The SREBP pathway: Regulation of cholesterol metabolism by proteolysis of a membrane-bound transcription factor. Cell 89:331-340. (Pubitemid 27220877)
13. Sun L-P, Seemann J, Goldstein JL, Brown MS (2007) Sterol-regulated transport of SREBPs from endoplasmic reticulum to Golgi: Insig renders sorting signal in Scap inaccessible to COPII proteins. Proc Natl Acad Sci USA 104:6519-6526. (Pubitemid 47175534)
14. Goldstein JL, DeBose-Boyd RA, Brown MS (2006) Protein sensors for membrane sterols. Cell 124:35-46.
15. Ferré P, Foufelle F (2010) Hepatic steatosis: A role for de novo lipogenesis and the transcription factor SREBP-1c. Diabetes Obes Metab 12(Suppl 2):83-92.
16. Wang X, Sato R, Brown MS, Hua X, Goldstein JL (1994) SREBP-1, a membrane-bound transcription factor released by sterol-regulated proteolysis. Cell 77:53-62.
17. Laplante M, Sabatini DM (2012) mTOR Signaling. Cold Spring Harb Perspect Biol 4: a011593.
18. Lu M, et al. (2012) Insulin regulates liver metabolism in vivo in the absence of hepatic Akt and Foxo1. Nat Med 18:388-395.
19. Yecies JL, et al. (2011) Akt stimulates hepatic SREBP1c and lipogenesis through parallel mTORC1-dependent and independent pathways. Cell Metab 14:21-32.
20. Bae EJ, et al. (2012) Liver-specific p70 S6 kinase depletion protects against hepatic steatosis and systemic insulin resistance. J Biol Chem 287:18769-18780.
21. Unger RH, Cherrington AD (2012) Glucagonocentric restructuring of diabetes: A pathophysiologic and therapeutic makeover. J Clin Invest 122:4-12.
22. Engelking LJ, et al. (2004) Overexpression of Insig-1 in the livers of transgenic mice inhibits SREBP processing and reduces insulin-stimulated lipogenesis. J Clin Invest 113:1168-1175. (Pubitemid 38544102)
23. Young SG, Lusis AJ, Hammer RE (1999) Molecular Basis of Cardiovascular Disease, ed Chien KR (W.B. Saunders Company, Philadelphia), pp 37-85.