| http://purl.uniprot.org/citations/16207722 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/16207722 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/16207722 | http://www.w3.org/2000/01/rdf-schema#comment | "The IkappaB kinase (IKK)/NF-kappaB and phosphatidylinositol 3-OH-kinase/3-phosphoinositide-dependent protein kinase-1 (PDK1)/Akt pathways regulate various cellular functions, especially cell survival. These two pathways are often activated in many tumors and are thought to be associated with tumor progression. However, the cross-talk between them remains unclear. Here we show that PDK1 can activate IKK/NF-kappaB signaling in addition to Akt signaling to promote cell survival. Screening kinases that could modulate NF-kappaB activity revealed that expression of an upstream Akt kinase PDK1 up-regulates NF-kappaB transcriptional activity. We found that PDK1 directly phosphorylates IKKbeta at the Ser(181) residue in the activation loop, leading to NF-kappaB nuclear translocation and NF-kappaB-dependent anti-apoptotic gene expression. IKKalpha is not required for PDK1-mediated NF-kappaB activation because NF-kappaB activation was observed in IKKalpha(-/-) mouse embryonic fibroblast (MEF) cells as in wild type MEF cells. Akt, which was previously reported to activate IKKalpha, did not participate in the PDK1-dependent IKKbeta or NF-kappaB activation. The siRNA-mediated PDK1 gene silencing attenuated NF-kappaB activity and increased TRAIL-mediated cytotoxicity. Moreover, expression of constitutively active IKKbeta overcame the PDK1 siRNA-mediated susceptibility to TRAIL. These results indicate that PDK1 is a critical regulator of cell survival by modulating the IKK/NF-kappaB pathway in addition to the Akt pathway."xsd:string |
| http://purl.uniprot.org/citations/16207722 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m506235200"xsd:string |
| http://purl.uniprot.org/citations/16207722 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m506235200"xsd:string |
| http://purl.uniprot.org/citations/16207722 | http://purl.uniprot.org/core/author | "Fujita N."xsd:string |
| http://purl.uniprot.org/citations/16207722 | http://purl.uniprot.org/core/author | "Fujita N."xsd:string |
| http://purl.uniprot.org/citations/16207722 | http://purl.uniprot.org/core/author | "Tanaka H."xsd:string |
| http://purl.uniprot.org/citations/16207722 | http://purl.uniprot.org/core/author | "Tanaka H."xsd:string |
| http://purl.uniprot.org/citations/16207722 | http://purl.uniprot.org/core/author | "Tsuruo T."xsd:string |
| http://purl.uniprot.org/citations/16207722 | http://purl.uniprot.org/core/author | "Tsuruo T."xsd:string |
| http://purl.uniprot.org/citations/16207722 | http://purl.uniprot.org/core/date | "2005"xsd:gYear |
| http://purl.uniprot.org/citations/16207722 | http://purl.uniprot.org/core/date | "2005"xsd:gYear |
| http://purl.uniprot.org/citations/16207722 | http://purl.uniprot.org/core/name | "J. Biol. Chem."xsd:string |
| http://purl.uniprot.org/citations/16207722 | http://purl.uniprot.org/core/name | "J. Biol. Chem."xsd:string |
| http://purl.uniprot.org/citations/16207722 | http://purl.uniprot.org/core/pages | "40965-40973"xsd:string |
| http://purl.uniprot.org/citations/16207722 | http://purl.uniprot.org/core/pages | "40965-40973"xsd:string |
| http://purl.uniprot.org/citations/16207722 | http://purl.uniprot.org/core/title | "3-Phosphoinositide-dependent protein kinase-1-mediated IkappaB kinase beta (IkkB) phosphorylation activates NF-kappaB signaling."xsd:string |
| http://purl.uniprot.org/citations/16207722 | http://purl.uniprot.org/core/title | "3-Phosphoinositide-dependent protein kinase-1-mediated IkappaB kinase beta (IkkB) phosphorylation activates NF-kappaB signaling."xsd:string |
| http://purl.uniprot.org/citations/16207722 | http://purl.uniprot.org/core/volume | "280"xsd:string |
| http://purl.uniprot.org/citations/16207722 | http://purl.uniprot.org/core/volume | "280"xsd:string |
| http://purl.uniprot.org/citations/16207722 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/16207722 |
| http://purl.uniprot.org/citations/16207722 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/16207722 |
| http://purl.uniprot.org/citations/16207722 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/16207722 |
| http://purl.uniprot.org/citations/16207722 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/16207722 |