Gene interactions and pathways from curated databases and text-mining
Mol Cell 2008, PMID: 18570873

mTOR-raptor binds and activates SGK1 to regulate p27 phosphorylation.

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

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-beta 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.

Diseases/Pathways annotated by Medline MESH: Melanoma
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Text Mining Data

SGK1 → mTOR-raptor: " mTOR-raptor binds and activates SGK1 to regulate p27 phosphorylation "

SGK1 → mTOR-raptor: " mTOR-raptor binds and activates SGK1 to regulate p27 phosphorylation "

SGK1 → mTOR: " 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 "

p27 → mTOR: " 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 "

SGK1 → mTOR: " mTOR overexpression activated both Akt and SGK1 , causing TGF-beta resistance through impaired nuclear import and cytoplasmic accumulation of p27 "

Akt → mTOR: " mTOR overexpression activated both Akt and SGK1, causing TGF-beta resistance through impaired nuclear import and cytoplasmic accumulation of p27 "

SGK1 → Akt: " Rapamycin or raptor shRNA impaired mTOR-driven p70 and SGK1 activation , but not that of Akt , and decreased cytoplasmic p27 "

Manually curated Databases

  • IRef Innatedb Interaction: AKT1S1 — MTOR (unknown, -)
In total, 1 gene pairs are associated to this article in curated databases