RRC ID 1606
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.
Abstract 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.
Volume 25(13)
Pages 5725-37
Published 2005-7
DOI 10.1128/MCB.25.13.5725-5737.2005
PII 25/13/5725
Description AKTによるWEE1のリン酸化とその影響を解析するためのヒトWEE1の部分欠失型及びアミノ酸置換型変異体発現ベクターの作製に使用されました。
PMID 15964826
PMC PMC1156994
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
IF 3.813
Times Cited 94
WOS Category BIOCHEMISTRY & MOLECULAR BIOLOGY CELL BIOLOGY
Resource
DNA material WEE1Hu (RDB1204)