Regulation of phosphoenolpyruvate carboxykinase (GTP) gene transcription

Author(s):  
J. Liu ◽  
R. W. Hanson
1994 ◽  
Vol 266 (4) ◽  
pp. E560-E566 ◽  
Author(s):  
J. E. Friedman

The objective of these studies was to determine the molecular basis for the activation of phosphoenolpyruvate carboxykinase (PEPCK) gene transcription during prolonged submaximal exercise. Mice were fed a high-carbohydrate diet for 1 wk and exercised continuously by swimming for up to 120 min. The level of hepatic PEPCK mRNA increased progressively during exercise, reaching 510% above control, whereas transcription of the PEPCK gene increased 1,000%, before decreasing to control levels within 60 min of recovery. In transgenic mice carrying a chimeric gene consisting of the PEPCK promoter linked to a reporter gene for bovine growth hormone (bGH), PEPCK(-460)-bGH, the level of hepatic bGH mRNA increased by 490% in response to exercise, similar to the increase in the expression of the native PEPCK gene. However, in transgenic mice with a deletion of the glucocorticoid regulatory unit, PEPCK(-355)-bGH, bGH mRNA did not increase above control values. In transgenic mice with a block mutation in adenosine 3',5'-cyclic monophosphate (cAMP) regulatory regions -90/-82 and -250/-234, PEPCK cAMP response element 1 (CRE-1)/P3(1)-bGH, exercise increased bGH mRNA 260% above controls. Adrenalectomy (Adx) had no effect on PEPCK mRNA levels in nonexercised mice, whereas in adrenalectomized (Adx)-exercised mice, PEPCK mRNA increased only 80% above basal, and, in Adx mice injected with dexamethasone, PEPCK mRNA increased with exercise 570% above controls. Exercise was also associated with a large increase in transcription of the gene for the transcription factor CCAAT/enhancer-binding protein beta (C/EBP-beta) and a smaller rise in transcription of c-jun gene, both of which returned to control levels during recovery.(ABSTRACT TRUNCATED AT 250 WORDS)


1998 ◽  
Vol 273 (48) ◽  
pp. 31629-31632 ◽  
Author(s):  
Colleen Croniger ◽  
Patrick Leahy ◽  
Lea Reshef ◽  
Richard W. Hanson

2001 ◽  
Vol 276 (37) ◽  
pp. 34816-34823 ◽  
Author(s):  
Kaushik Chakravarty ◽  
Patrick Leahy ◽  
Dominique Becard ◽  
Parvin Hakimi ◽  
Marc Foretz ◽  
...  

1996 ◽  
Vol 351 (1336) ◽  
pp. 191-199 ◽  

Phosphoenolpyruvate carboxykinase (PEPCK) catalyses the rate-limiting step in hepatic gluconeogenesis. Glucagon (via the second messenger cAMP) and glucocorticoids stimulate transcription of the PEPCK gene whereas insulin and phorbol esters have a dominant inhibitory effect. Wortmannin, an inhibitor of 1-phosphatidylinositol 3-kinase (PI 3-kinase), blocks the inhibition of glucocorticoid- and cAMP stimulated PEPCK gene transcription by insulin. By contrast, although phorbol esters mimic the action of insulin on the regulation of PEPCK gene transcription, wortmannin does not block the effect of these agents. Thus PI 3-kinase is required for the regulation of PEPCK gene expression by insulin but not by phorbol esters. In liver cells, insulin administration stimulates the activity of multiple protein kinases, including the p42/p44 Mitogen Activated Protein (MAP) kinase and the p70/p85 ribosomal protein S6 kinase. Selective inhibition of the activation of either kinase, utilizing the compounds PD98059 and rapamycin respectively, does not affect insulin regulation of PEPCK gene transcription. Thus regulation of PEPCK gene transcription requires PI 3-kinase but does not require the activation of either p42/p44 MAP kinase or p70/p85 ribosomal protein S6 kinase.


1997 ◽  
Vol 272 (50) ◽  
pp. 31475-31481 ◽  
Author(s):  
Jacob E. Friedman ◽  
Yang Sun ◽  
Tatsuya Ishizuka ◽  
Craig J. Farrell ◽  
Shana E. McCormack ◽  
...  

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