Reference - Detail
|Author||Katayama K, Fujita N, Tsuruo T.|
|Title||Akt/protein kinase B-dependent phosphorylation and inactivation of WEE1Hu promote cell cycle progression at G2/M transition.|
|Journal||Mol Cell Biol|
The serine/threonine kinase Akt is known to promote cell growth by regulating the cell cycle in G1 phase through activation of cyclin/Cdk kinases and inactivation of Cdk inhibitors. However, how the G2/M phase is regulated by Akt remains unclear. Here, we show that Akt counteracts the function of WEE1Hu. Inactivation of Akt by chemotherapeutic drugs or the phosphatidylinositide-3-OH kinase inhibitor LY294002 induced G2/M arrest together with the inhibitory phosphorylation of Cdc2. Because the increased Cdc2 phosphorylation was completely suppressed by wee1hu gene silencing, WEE1Hu was associated with G2/M arrest induced by Akt inactivation. Further analyses revealed that Akt directly bound to and phosphorylated WEE1Hu during the S to G2 phase. Serine-642 was identified as an Akt-dependent phosphorylation site. WEE1Hu kinase activity was not affected by serine-642 phosphorylation. We revealed that serine-642 phosphorylation promoted cytoplasmic localization of WEE1Hu. The nuclear-to-cytoplasmic translocation was mediated by phosphorylation-dependent WEE1Hu binding to 14-3-3theta but not 14-3-3beta or -sigma. These results indicate that Akt promotes G2/M cell cycle progression by inducing phosphorylation-dependent 14-3-3theta binding and cytoplasmic localization of WEE1Hu.
|MeSH||Cell Cycle / physiology* Cell Cycle Proteins / genetics Cell Cycle Proteins / metabolism* Cell Division* Cell Line Cell Line, Tumor Cell Nucleus / metabolism Cytoplasm / metabolism G2 Phase* HeLa Cells Humans Kidney / cytology Kidney / embryology Nuclear Proteins / genetics Nuclear Proteins / metabolism* Phosphorylation Protein Binding Protein-Serine-Threonine Kinases / metabolism* Protein-Tyrosine Kinases / genetics Protein-Tyrosine Kinases / metabolism* Proto-Oncogene Proteins / metabolism* Proto-Oncogene Proteins c-akt|
|WOS Category||BIOCHEMISTRY & MOLECULAR BIOLOGY CELL BIOLOGY|
|DNA material||WEE1Hu (RDB1204)|