Biochem J 2001,
PMID: 11672436
Patel, S; Lochhead, P A; Rena, G; Sutherland, C
Glucose-6-phosphatase (G6Pase) and insulin-like growth factor-binding protein-1 (IGFBP-1) genes contain a homologous promoter sequence that is required for gene repression by insulin. Interestingly, this element interacts with members of the forkhead family of transcription factors [e.g. HNF3 (hepatic nuclear factor 3), FKHR (forkhead in rhabdomyosarcoma)] in vitro, while insulin promotes the phosphorylation and inactivation of FKHR in a phosphatidylinositol 3-kinase- and protein kinase B (PKB)-dependent manner. This mechanism has been proposed to underlie insulin action on G6Pase and IGFBP-1 gene transcription. However, we find that treatment of cells with phorbol esters mimics the effect of insulin on G6Pase, but not IGFBP-1, gene expression. Indeed, phorbol ester treatment actually blocks the ability of insulin to repress IGFBP-1 gene expression. In addition, the action of phorbol esters is significantly reduced by inhibition of the p42/p44 mitogen-activated protein (MAP) kinase pathway. However insulin-induced phosphorylation of PKB or FKHR is not affected by the presence of phorbol esters. Therefore we suggest that activation of p42/p44 MAP kinases will reduce the sensitivity of the IGFBP-1 gene promoter, but not the G6Pase gene promoter, to insulin. Importantly, the activation of PKB and phosphorylation of FKHR is not, in itself, sufficient to reduce IGFBP-1 gene expression in the presence of phorbol esters.
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Text Mining Data
G6Pase — insulin: "
This mechanism has been proposed to underlie
insulin action on
G6Pase and IGFBP-1 gene transcription
"
IGFBP-1 — insulin: "
This mechanism has been proposed to underlie insulin action on G6Pase and IGFBP-1 gene transcription
"
G6Pase — insulin: "
However, we find that treatment of cells with phorbol esters mimics the effect of insulin on G6Pase , but not IGFBP-1, gene expression
"
FKHR → insulin: "
However insulin induced phosphorylation of PKB or FKHR is not affected by the presence of phorbol esters
"
PKB → insulin: "
However insulin induced phosphorylation of PKB or FKHR is not affected by the presence of phorbol esters
"
IGFBP-1 ⊣ FKHR: "
Importantly, the activation of PKB and phosphorylation of FKHR is not, in itself, sufficient to reduce IGFBP-1 gene expression in the presence of phorbol esters
"
IGFBP-1 ⊣ PKB: "
Importantly, the activation of PKB and phosphorylation of FKHR is not, in itself, sufficient to reduce IGFBP-1 gene expression in the presence of phorbol esters
"
Manually curated Databases
-
IRef Hprd Interaction:
G6PC
—
FOXO1
(in vitro)
-
IRef Ophid Interaction:
G6PC
—
FOXO1
(aggregation, confirmational text mining)
In total, 1 gene pairs are associated to this article in curated databases