Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.1.3.9 (
glucose-6-phosphatase
)
3,081
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Expression of
glucose-6-phosphatase
(
G6Pase
), one of the rate-limiting enzymes of hepatic gluconeogenesis, has recently been shown to be transactivated by the transcription factor FKHR. One of the proteins known to directly interact with FKHR is the nuclear protein kinase DYRK1A. In order to study the effects of DYRK1A on
G6Pase
gene expression, we generated a H4IIEC3 rat hepatoma cell line stably expressing DYRK1A by retroviral infection. Overexpression of DYRK1A increased the expression of
G6Pase
about threefold, as determined by Northern blotting. In transiently transfected HepG2 cells, co-expression of DYRK1A and a
G6Pase
promoter construct increased
G6Pase
promoter activity about twofold. This effect of DYRK1A was independent of its kinase activity, since a kinase-dead DYRK1A mutant as well as a point mutant of the phosphorylation site of DYRK1A in FKHR (Ser329Ala) failed to affect the effect of DYRK1A on the
G6Pase
expression. The effect of
DYRK
on the
G6Pase
promoter activity was produced by the isoforms DYRK1A and DYRK1B, which are localized in the nucleus, but not by DYRK2. Mutations of the FKHR-binding sites in the
G6Pase
promoter markedly reduced the effect of
DYRK1
on the
G6Pase
promoter activity. In summary, the data suggest that
DYRK1
is a specific co-activator of FKHR, independent of its kinase activity.
...
PMID:DYRK1 is a co-activator of FKHR (FOXO1a)-dependent glucose-6-phosphatase gene expression. 1250 16
