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
