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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
39
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pubmed:dateCreated |
2004-9-20
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pubmed:abstractText |
Full activation of protein kinase B (PKB)/Akt requires phosphorylation on Thr-308 and Ser-473 by 3-phosphoinositide-dependent kinase-1 (PDK1) and Ser-473 kinase (S473K), respectively. Although PDK1 has been well characterized, the identification of the S473K remains controversial. A major PKB Ser-473 kinase activity was purified from the membrane fraction of HEK293 cells and found to be DNA-dependent protein kinase (DNA-PK). DNA-PK co-localized and associated with PKB at the plasma membrane. In vitro, DNA-PK phosphorylated PKB on Ser-473, resulting in a approximately 10-fold enhancement of PKB activity. Knockdown of DNA-PK by small interfering RNA inhibited Ser-473 phosphorylation induced by insulin and pervanadate. DNA-PK-deficient glioblastoma cells did not respond to insulin at the level of Ser-473 phosphorylation; this effect was restored by complementation with the human PRKDC gene. We conclude that DNA-PK is a long sought after kinase responsible for the Ser-473 phosphorylation step in the activation of PKB.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/AKT1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/DNA, Complementary,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Activated Protein Kinase,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Insulin,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/PRKDC protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Prkdc protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-akt,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Serine,
http://linkedlifedata.com/resource/pubmed/chemical/Vanadates,
http://linkedlifedata.com/resource/pubmed/chemical/pervanadate
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:copyrightInfo |
Copyright 2004 American Society for Biochemistry and Molecular Biology, Inc.
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pubmed:issnType |
Print
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pubmed:day |
24
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pubmed:volume |
279
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
41189-96
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:15262962-3T3-L1 Cells,
pubmed-meshheading:15262962-Amino Acid Motifs,
pubmed-meshheading:15262962-Animals,
pubmed-meshheading:15262962-Cell Line,
pubmed-meshheading:15262962-Cell Line, Tumor,
pubmed-meshheading:15262962-Cell Membrane,
pubmed-meshheading:15262962-Chromatography, Gel,
pubmed-meshheading:15262962-DNA, Complementary,
pubmed-meshheading:15262962-DNA-Activated Protein Kinase,
pubmed-meshheading:15262962-DNA-Binding Proteins,
pubmed-meshheading:15262962-Enzyme Activation,
pubmed-meshheading:15262962-Genetic Complementation Test,
pubmed-meshheading:15262962-Glioblastoma,
pubmed-meshheading:15262962-Humans,
pubmed-meshheading:15262962-Insulin,
pubmed-meshheading:15262962-Mice,
pubmed-meshheading:15262962-Microscopy, Fluorescence,
pubmed-meshheading:15262962-Models, Biological,
pubmed-meshheading:15262962-Nuclear Proteins,
pubmed-meshheading:15262962-Phosphorylation,
pubmed-meshheading:15262962-Plasmids,
pubmed-meshheading:15262962-Precipitin Tests,
pubmed-meshheading:15262962-Protein-Serine-Threonine Kinases,
pubmed-meshheading:15262962-Proto-Oncogene Proteins,
pubmed-meshheading:15262962-Proto-Oncogene Proteins c-akt,
pubmed-meshheading:15262962-Recombinant Proteins,
pubmed-meshheading:15262962-Serine,
pubmed-meshheading:15262962-Time Factors,
pubmed-meshheading:15262962-Transfection,
pubmed-meshheading:15262962-Vanadates
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pubmed:year |
2004
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pubmed:articleTitle |
Identification of a PKB/Akt hydrophobic motif Ser-473 kinase as DNA-dependent protein kinase.
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pubmed:affiliation |
Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, Basel CH-4058, Switzerland.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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