mTOR-Raptor Binds and Activates SGK1 to Regulate p27 Phosphorylation

Feng Hong, Michelle D. Larrea, Cheryl Doughty, David J. Kwiatkowski, Rachel Squillace, Joyce M. Slingerland

Research output: Contribution to journalArticle

190 Scopus citations

Abstract

The cell-cycle effects of mTORC1 are not fully understood. We provide evidence that mTOR-raptor phosphorylates SGK1 to modulate p27 function. Cellular mTOR activation, by refeeding of amino acid-deprived cells or by TSC2 shRNA, activated SGK1 and p27 phosphorylation at T157, and both were inhibited by short-term rapamycin treatment and by SGK1 shRNA. mTOR overexpression activated both Akt and SGK1, causing TGF-β resistance through impaired nuclear import and cytoplasmic accumulation of p27. Rapamycin or raptor shRNA impaired mTOR-driven p70 and SGK1 activation, but not that of Akt, and decreased cytoplasmic p27. mTOR/raptor/SGK1 complexes were detected in cells. mTOR phosphorylated SGK1, but not SGK1-S422A, in vitro. SGK1 phosphorylated p27 in vitro. These data implicate SGK1 as an mTORC1 (mTOR-raptor) substrate. mTOR may promote G1 progression in part through SGK1 activation and deregulate the cell cycle in cancers through both Akt- and SGK-mediated p27 T157 phosphorylation and cytoplasmic p27 mislocalization.

Original languageEnglish (US)
Pages (from-to)701-711
Number of pages11
JournalMolecular Cell
Volume30
Issue number6
DOIs
StatePublished - Jun 20 2008

Keywords

  • CELLCYCLE
  • SIGNALING

ASJC Scopus subject areas

  • Molecular Biology

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    Hong, F., Larrea, M. D., Doughty, C., Kwiatkowski, D. J., Squillace, R., & Slingerland, J. M. (2008). mTOR-Raptor Binds and Activates SGK1 to Regulate p27 Phosphorylation. Molecular Cell, 30(6), 701-711. https://doi.org/10.1016/j.molcel.2008.04.027