Akt/protein kinase B-dependent phosphorylation and inactivation of WEE1Hu promote cell cycle progression at G2/M transition

Kazuhiro Katayama, Naoya Fujita, Takashi Tsuruo

Research output: Contribution to journalArticle

112 Citations (Scopus)

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 G 2/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 G 2/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 14-3-3θ but not 14-3-3β or -σ. These results indicate that Akt promotes G2/M cell cycle progression by inducing phosphorylation-dependent 14-3-3θ binding and cytoplasmic localization of WEE1Hu.

Original languageEnglish
Pages (from-to)5725-5737
Number of pages13
JournalMolecular and Cellular Biology
Volume25
Issue number13
DOIs
Publication statusPublished - 2005 Jul
Externally publishedYes

Fingerprint

Proto-Oncogene Proteins c-akt
Cell Cycle
Phosphorylation
Serine
Phosphotransferases
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
Cyclins
G2 Phase
Protein-Serine-Threonine Kinases
G1 Phase
Gene Silencing
Cell Division
Growth
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Akt/protein kinase B-dependent phosphorylation and inactivation of WEE1Hu promote cell cycle progression at G2/M transition. / Katayama, Kazuhiro; Fujita, Naoya; Tsuruo, Takashi.

In: Molecular and Cellular Biology, Vol. 25, No. 13, 07.2005, p. 5725-5737.

Research output: Contribution to journalArticle

Katayama, Kazuhiro ; Fujita, Naoya ; Tsuruo, Takashi. / Akt/protein kinase B-dependent phosphorylation and inactivation of WEE1Hu promote cell cycle progression at G2/M transition. In: Molecular and Cellular Biology. 2005 ; Vol. 25, No. 13. pp. 5725-5737.
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