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:1.6.3.1 (
NADPH oxidase
)
11,281
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Reactive oxygen species (ROS) produced by
NADPH oxidase
function as defence and signalling molecules related to innate immunity and various cellular responses. The activation of
NADPH oxidase
in response to plasma membrane receptor activation depends on the phosphorylation of cytoplasmic oxidase subunits, their translocation to membranes and the assembly of all
NADPH oxidase
components. Tumour necrosis factor (TNF) is a prominent stimulus of ROS production, but the molecular mechanisms by which TNF activates
NADPH oxidase
are poorly understood. Here we identify riboflavin kinase (
RFK
, formerly known as
flavokinase
) as a previously unrecognized TNF-receptor-1 (TNFR1)-binding protein that physically and functionally couples TNFR1 to
NADPH oxidase
. In mouse and human cells,
RFK
binds to both the TNFR1-death domain and to p22(phox), the common subunit of
NADPH oxidase
isoforms.
RFK
-mediated bridging of TNFR1 and p22(phox) is a prerequisite for TNF-induced but not for Toll-like-receptor-induced ROS production. Exogenous flavin mononucleotide or FAD was able to substitute fully for TNF stimulation of
NADPH oxidase
in
RFK
-deficient cells.
RFK
is rate-limiting in the synthesis of FAD, an essential prosthetic group of
NADPH oxidase
. The results suggest that TNF, through the activation of
RFK
, enhances the incorporation of FAD in
NADPH oxidase
enzymes, a critical step for the assembly and activation of
NADPH oxidase
.
...
PMID:Riboflavin kinase couples TNF receptor 1 to NADPH oxidase. 1964 94
