scholarly journals Protein kinase Cbeta mediates hepatic induction of sterol-regulatory element binding protein-1c by insulin

2010 ◽  
Vol 51 (7) ◽  
pp. 1859-1870 ◽  
Author(s):  
Takashi Yamamoto ◽  
Kazuhisa Watanabe ◽  
Noriyuki Inoue ◽  
Yoshimi Nakagawa ◽  
Naomi Ishigaki ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Binding Protein ◽  
Regulatory Element ◽  
Element Binding Protein ◽  
Sterol Regulatory Element

scholarly journals Analysis of the role of protein kinase B (cAKT) in insulin-dependent induction of glucokinase and sterol regulatory element-binding protein 1 (SREBP1) mRNAs in hepatocytes

2003 ◽  
Vol 376 (3) ◽  
pp. 697-705 ◽  
Author(s):  
Pascale G. RIBAUX ◽  
Patrick B. IYNEDJIAN
Keyword(s):  
Protein Kinase ◽  
Protein Kinase B ◽  
Binding Protein ◽  
Regulatory Element ◽  
Necessary Condition ◽  
Insulin Effect ◽  
Element Binding Protein ◽  
Insulin Dependent ◽  
Sterol Regulatory Element ◽  
Stimulation Of

Previous work showed that acute stimulation of a conditionally active protein kinase B (PKB or cAKT) was sufficient to elicit insulin-like induction of GCK (glucokinase) and SREBP1 (sterol regulatory element-binding protein 1) in hepatocytes [Iynedjian, Roth, Fleischmann and Gjinovci (2000) Biochem. J. 351, 621–627; Fleischmann and Iynedjian (2000) Biochem. J. 349, 13–17]. The objective of the present study was to determine whether activation of PKB during insulin stimulation of hepatocytes was a necessary condition for the induction of the two genes. Activation of PKB by insulin was inhibited by pretreatment of the hepatocytes with C2 ceramide. This resulted in the inhibition of insulin-dependent increases in GCK and SREBP1 mRNAs. A triple mutant of PKB failed to interfere with insulin activation of PKB in hepatocytes even at high overexpression levels achieved after adenovirus transduction. A PKB–CaaX fusion protein, which can act as a dominant-negative inhibitor of PKB activation in other cells, was shown to be constitutively activated in hepatocytes and to trigger insulin-like induction of GCK and SREBP1. In addition, constitutive PKB–CaaX activity caused refractoriness of the hepatocytes to insulin signalling at an upstream step resulting in the inhibition of both extracellular-signal-regulated kinase 1/2 and endogenous PKB activation. The stimulation of gene expression by constitutively active PKB–CaaX and inhibition of the insulin effect by ceramide are compatible with a role for PKB in the insulin-dependent induction of GCK and SREBP1.

scholarly journals Protein Kinase A Suppresses Sterol Regulatory Element-binding Protein-1C Expression via Phosphorylation of Liver X Receptor in the Liver

2007 ◽  
Vol 282 (16) ◽  
pp. 11687-11695 ◽  
Author(s):  
Takashi Yamamoto ◽  
Hitoshi Shimano ◽  
Noriyuki Inoue ◽  
Yoshimi Nakagawa ◽  
Takashi Matsuzaka ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Binding Protein ◽  
Regulatory Element ◽  
Liver X Receptor ◽  
Element Binding Protein ◽  
Sterol Regulatory Element ◽  
Kinase A

Regulation of sterol regulatory-element binding protein 1 gene expression in liver: role of insulin and protein kinase B/cAkt

2000 ◽  
Vol 349 (1) ◽  
pp. 13-17 ◽  
Author(s):  
Mark FLEISCHMANN ◽  
Patrick B. IYNEDJIAN
Keyword(s):  
Gene Expression ◽  
Protein Kinase ◽  
Recombinant Protein ◽  
Protein Kinase B ◽  
Binding Protein ◽  
Regulatory Element ◽  
Mutant Form ◽  
Element Binding Protein ◽  
Sterol Regulatory Element

Insulin stimulates the transcription of the sterol regulatory- element binding protein (SREBP) 1/ADD1 gene in liver. Hepatocytes in primary culture were used to delineate the insulin signalling pathway for induction of SREBP1 gene expression. The inhibitors of phosphoinositide 3-kinase (PI 3-kinase), wortmannin and LY 294002, abolished the insulin-dependent increase in SREBP1 mRNA, whereas the inhibitor of the mitogen- activated protein kinase cascade, PD 98059, was without effect. To investigate the role of protein kinase B (PKB)/cAkt downstream of PI 3-kinase, hepatocytes were transduced with an adenovirus encoding a PKB-oestrogen receptor fusion protein. The PKB activity of this recombinant protein was rapidly activated in hepatocytes challenged with 4-hydroxytamoxifen (OHT), as was endogenous PKB in hepatocytes challenged with insulin. The addition of OHT to transduced hepatocytes resulted in accumulation of SREBP1 mRNA, with a time-course and magnitude similar to the effect of insulin in non-transduced cells. The level of SREBP1 mRNA was not increased by OHT in hepatocytes expressing a mutant form of the recombinant protein whose PKB activity was not activated by OHT. Thus acute activation of PKB is sufficient to induce SREBP1 mRNA accumulation in primary hepatocytes, and might be the major signalling event by which insulin induces SREBP1 gene expression in the liver.

Dehydroepiandrosterone activates cyclic adenosine 3′,5′-monophosphate/protein kinase A signalling and suppresses sterol regulatory element-binding protein-1 expression in cultured primary chicken hepatocytes

2009 ◽  
Vol 102 (5) ◽  
pp. 680-686 ◽  
Author(s):  
Xue Tang ◽  
Haitian Ma ◽  
Zanming Shen ◽  
Sixiang Zou ◽  
Xijie Xu ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Binding Protein ◽  
Regulatory Element ◽  
Fat Deposition ◽  
Metabolic Efficiency ◽  
Intracellular Camp ◽  
Element Binding Protein ◽  
Sterol Regulatory Element ◽  
Kinase A

Dehydroepiandrosterone (DHEA), a steroid hormone that is secreted by the adrenal cortex in mammals, has an array of biological actions, including inhibition of fat synthesis, decreasing the number of adipocytes, and a reduction in mammalian metabolic efficiency. Recent studies showed that DHEA may decrease fat deposition in poultry, but the mechanism of action is unclear. In the present study, we demonstrate that DHEA stimulates intracellular cyclic adenosine 3′,5′-monophosphate (cAMP) accumulation in chicken hepatocytes during a 30 min incubation period. Increases in intracellular cAMP are evoked by as low as 0·1 μm-DHEA. The cAMP induced by DHEA, while suppressing cAMP-specific phosphodiesterase activity, also activates cAMP-dependent protein kinase A (PKA) in chicken hepatocytes. In addition, the activation of PKA leads to down-regulation of sterol regulatory element-binding protein-1 (SREBP-1). These findings demonstrate that direct action by DHEA leads to activation of the cAMP/PKA signalling system in the modulation of lipid metabolism by repressing SREBP-1, thereby providing a novel explanation for some of the underlying effects proposed for DHEA in the prevention of fat deposition in poultry.

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