Format

Send to:

Choose Destination
See comment in PubMed Commons below
Biochim Biophys Acta. 2013 Oct;1833(10):2135-42. doi: 10.1016/j.bbamcr.2013.05.005. Epub 2013 May 13.

Inhibition of 14-3-3 binding to Rictor of mTORC2 for Akt phosphorylation at Ser473 is regulated by selenoprotein W.

Author information

  • 1School of Life Sciences and Biotechnology, Korea University, Sungbuk-Ku, Seoul, Republic of Korea.

Abstract

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.

Copyright © 2013 Elsevier B.V. All rights reserved.

KEYWORDS:

14-3-3; Akt; GSH; NMR; Nuclear magnetic resonance spectroscopy; Rapamycin-insensitive companion of mTOR; Rictor; Sec, U; Selenocysteine; Selenoprotein W; Trx; glutathione; mTOR; mammalian target of rapamycin; s.d.; standard deviation; thioredoxin

PMID:
23680186
[PubMed - indexed for MEDLINE]
Free full text
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science
    Loading ...
    Write to the Help Desk