Xylulose 5-phosphate mediates glucose-induced lipogenesis by xylulose 5-phosphate-activated protein phosphatase in rat liver.

作者: T. Kabashima , T. Kawaguchi , B. E. Wadzinski , K. Uyeda

DOI: 10.1073/PNAS.0730817100

关键词: Xylulose 5-phosphateXylulosePhosphataseDephosphorylationBiochemistryLipogenesisProtein kinase ACarbohydrate-responsive element-binding proteinPyruvate kinaseBiologyMolecular biology

摘要: Carbohydrate-responsive element binding protein (ChREBP) is a transcription factor that activates lipogenic genes in liver response to excess carbohydrate the diet. ChREBP regulated reciprocal manner by glucose and cAMP. cAMP-dependent kinase (protein A) phosphorylates two physiologically important sites ChREBP, Ser-196, which located near nuclear localization signal sequence (NLS), Thr-666, within basic helix–loop–helix (bHLH) site, resulting inactivation of translocation DNA-binding activity, respectively. We demonstrate here crude cytosolic extracts from livers rats fed high diet contained phosphatase (PPase) activity dephosphorylated peptide containing whereas PPase extract catalyzed dephosphorylation Ser-568 Thr-666. All these PPases are activated specifically xylulose 5-phosphate (Xu5P), but not other sugar phosphates. Furthermore, addition Xu5P elevated level observed cells. These partially purified were characterized as PP2A-ABδC immunoblotting with specific antibodies. results suggest (ia) Xu5P-dependent responsible for activation L-type pyruvate gene enzyme genes, (ii) signaling compound. Thus, we propose same Xu5P-activated controls both acute long-term regulation metabolism fat synthesis.

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