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Gene/Protein
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Target Concepts:
Gene/Protein
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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
A20
IIA1.6 B cells cotransfected with FcalphaR and wild-type gamma-chain (wt-ITAM (immunoreceptor tyrosine-based activation motif)) or FcalphaR and gamma-chain, in which the wt-ITAM was substituted with the FcgammaRIIA ITAM (IIA-ITAM), were used to investigate cell signaling events influencing presentation of FcalphaR-targeted exogenous Ag in the context of MHC class II. wt-ITAM cells presented FcalphaR-targeted OVA more efficiently than IIA-ITAM transfectants to OVA-specific T cell hybridomas. Phosphatidylinositol 3-kinase (PI 3-kinase) inhibition abrogated Ag presentation, suggesting that FcalphaR may trigger a PI 3-kinase-dependent signal transduction pathway, and thus phosphatidylinositol-dependent protein kinase (
PDK1
) and protein kinase B alpha (PKBalpha) activation. Cross-linking FcalphaR on wt-ITAM or IIA-ITAM cells triggered equivalent PI 3-kinase-dependent activation of PKBalpha. Furthermore, FcalphaR cross-linking triggered recruitment of
PDK1
and serine-phosphorylated PKBalpha to capped cell surface FcalphaR irrespective of the gamma-chain ITAM. Although FcalphaR endocytosis was accompanied by translocation of
PDK1
and phospho-PKBalpha to FcalphaR-containing vesicles in both transfectants, this was decreased in IIA-ITAM cells, and a significant proportion of
PDK1
and PKBalpha remained at the plasma membrane. In wt-ITAM cells,
PDK1
and serine-phosphorylated PKBalpha translocated to lysosomal-associated membrane glycoprotein 1- and cathepsin B-containing vesicles, consistent with MHC class II peptide-loading compartments (MIIC) described by other groups. Our data indicate that translocation of signal transduction mediators to MIIC-like compartments accompanies efficient presentation of receptor-targeted Ag, and suggest a mechanism connecting signaling to the Ag-processing pathway.
...
PMID:Fc alpha receptor cross-linking causes translocation of phosphatidylinositol-dependent protein kinase 1 and protein kinase B alpha to MHC class II peptide-loading-like compartments. 1131 98
