Biochim Biophys Acta 2013,
PMID: 23680186
Jeon, Yeong Ha; Park, Yong Hwan; Kwon, Joon Hyun; Lee, Jea Hwang; Kim, Ick Young
14-3-3 reduces cell proliferation by inhibiting the activity of proteins involved in the signaling pathway that includes Akt kinase. Activation of Akt is enhanced by activating the mammalian target of rapamycin complex 2 (mTORC2). 14-3-3 is also a negative regulator of the mTORC2/Akt pathway, by interacting with a component of mTORC2. Recently, we reported that selenoprotein W (SelW) regulated the interaction between 14-3-3 and its target protein, CDC25B. Here, we show that the binding of Rictor, a component of mTORC2, to 14-3-3, is regulated by the interaction of 14-3-3 with SelW. When SelW was down-regulated, mTORC2-dependent phosphorylation of Akt at Ser473 was decreased. However, the phosphorylation of Thr308 was not affected. The interaction of Rictor with 14-3-3 was increased in SelW-knockdown cells, as compared to control cells. SelW-knockdown cells were also more sensitive to DNA damage induced by etoposide, than control cells. This phenomenon was due to the decreased phosphorylation of Akt at Ser473. We also found that ectopic expression of SelW(U13C) reduced the interaction between Rictor and 14-3-3, leading to Akt phosphorylation at Ser473. Taken together, these findings demonstrate that SelW activates the mTORC2/Akt pathway for Akt phosphorylation at Ser473, by interrupting the binding of Rictor to 14-3-3.
Diseases/Pathways annotated by Medline MESH: Breast Neoplasms, Lung Neoplasms
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Text Mining Data
Akt → mammalian target of rapamycin: "
Activation of
Akt is
enhanced by activating the
mammalian target of rapamycin complex 2 ( mTORC2 )
"
Rictor → SelW: "
Here, we show that the binding of Rictor , a component of mTORC2, to 14-3-3, is regulated by the interaction of 14-3-3 with SelW
"
Akt → mTORC2: "
When SelW was down-regulated, mTORC2 dependent phosphorylation of Akt at Ser473 was decreased
"
Rictor ⊣ SelW: "
We also found that ectopic expression of SelW ( U13C ) reduced the interaction between Rictor and 14-3-3, leading to Akt phosphorylation at Ser473
"
Manually curated Databases
No curated data.