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:2.7.11.2 (
PDK1
)
2,238
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Phosphoinositide-dependent kinase (
PDK1
) regulates a number of pathways involved in responses to stress and in growth factor signaling; however, little is known concerning the mechanisms governing the activity of
PDK1
. In this report, we find that oxidative stress (H(2)O(2)) and vanadate induce tyrosine phosphorylation of
PDK1
. These effects of H(2)O(2) and vanadate were found in 293T cells and CH310T1/2 cells expressing exogenous
PDK1
and in A20 lymphoma cells expressing endogenous
PDK1
. Exogenously expressed
PDK1
was also tyrosine-phosphorylated in response to NGF treatment of 293T expressing TrkA. H(2)O(2) induced a more rapid tyrosine phosphorylation of
PDK1
relative to vanadate, and only vanadate-induced tyrosine phosphorylation of
PDK1
was sensitive to pretreatment of cells with wortmannin. In vitro,
PDK1
could be tyrosine-phosphorylated by both the c-Src and Abl tyrosine kinases. Both H(2)O(2) and vanadate treatments increased the activity of
PDK1
when the
serum/glucocorticoid regulated kinase
(
SGK
) was used as substrate. Vanadate treatment appeared to bypass the requirement for phosphatidylinositol 3,4,5-trisphosphate when Akt was used as substrate for
PDK1
. Tyrosine phosphorylation of
PDK1
by the Abl tyrosine kinase also increased the activity of
PDK1
toward
SGK
and Akt. These data suggest a novel mechanism through which
PDK1
activity may be regulated.
...
PMID:Oxidative stress and vanadate induce tyrosine phosphorylation of phosphoinositide-dependent kinase 1 (PDK1). 1084 74
