PMID: 25738366Mar 5, 2015Paper

Rapamycin inhibits mSin1 phosphorylation independently of mTORC1 and mTORC2

Oncotarget
Yan LuoShile Huang

Abstract

Current knowledge indicates that the mammalian target of rapamycin (mTOR) functions as two complexes, mTORC1 and mTORC2, regulating cell growth, proliferation, survival, differentiation, and motility. Recently mSin1 has been identified as a critical component of mTORC2, which is essential for phosphorylation of Akt and other signaling molecules. Studies have shown that rapamycin inhibits phosphorylation of mSin1. However, the underlying mechanism is unknown. Here we found that rapamycin inhibited phosphorylation of mSin1 potently and rapidly. Expression of rapamycin-resistant mutant of mTOR (mTOR-T), but not rapamycin-resistant and kinase dead mutant of mTOR (mTOR-TE), prevented rapamycin from inhibiting mSin1 phosphorylation, suggesting that rapamycin-induced dephosphorylation of mSin1 is mTOR-dependent. Surprisingly, ectopic expression of rapamycin-resistant and constitutively active p70 S6 kinase 1 (S6K1) did not confer resistance to rapamycin-induced dephosphorylation of mSin1. Furthermore, disruption of mTORC1 and mTORC2 by silencing raptor and rictor, respectively, or downregulation of S6K1 or Akt did not induce the dephosphorylation of mSin1 as rapamycin did. However, silencing mTOR or mLST8 mimicked the effect of rapamy...Continue Reading

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Citations

Feb 19, 2019·Journal of Experimental Botany·Marie-Hélène Montané, Benoît Menand
Jul 7, 2017·Genes & Cancer·Tao ShenShile Huang
Sep 6, 2017·British Journal of Cancer·Mansoureh BarzegarShile Huang
Nov 27, 2015·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Adrian M EidenBeverly A Mock
Jul 3, 2019·Biochimie·Laura PriorettiBrigitte Gontero

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