Two TOR complexes, only one of which is rapamycin sensitive, have distinct roles in cell growth control.

By R. Loewith, E. Jacinto, S. Wullschleger, A. Lorberg, J. Crespo, D. Bonenfant, W. Oppliger, P. Jenoe, Michael N. Hall. Molecules and Cells, 2002

1,926 citations recorded by the source corpus.

Subfields: Molecular Biology, Pharmacology

View Paper: https://www.semanticscholar.org/paper/59df10184bdfdffdd457f8af2a87d4f9e8c87dd4

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Molecular Biology

In Pharmacology

Citations in the corpus

mSin1 is necessary for Akt/PKB phosphorylation, and its isoforms define three distinct mTORC2s. (2006, background): “Although an interaction between mSin1 and mTOR was suspected, a previous attempt to show this association was unsuccessful [8], and thus our work provides the first evidence that endogenous mSin1 is a component of mTORC2 but not mTORC1.”
mTOR regulation of autophagy (2010, background): “Both TOR proteins bind KOG1, LST8, and TCO89, whereas TOR2 also binds LST8, Avo1, Avo2, Avo3, and BIT61 to form a separate protein complex [4,7].”
Active-Site Inhibitors of mTOR Target Rapamycin-Resistant Outputs of mTORC1 and mTORC2 (2009, background): “Fibers TORC2 is required for the generation of a polarized actin cytoskeleton in yeast [35].”
mTOR kinase structure, mechanism and regulation by the rapamycin-binding domain (2013, background): “Discovery of 9-(6-aminopyridin-3-yl)-1-(3-(trifluoromethyl) phenyl)benzo[h][1,6]naphthyridin-2(1H)-one (Torin2) as a potent, selective, and orally available mammalian target of rapamycin (mTOR) inhibitor for treatment of cancer.”
Mammalian TOR complex 2 controls the actin cytoskeleton and is rapamycin insensitive (2004, background): “In the budding yeast Saccharomyces cerevisiae , TOR is found in two distinct multi-protein complexe”
TOR signaling in growth and metabolism. (2006, methodology): “Biochemical purification of TOR1 and TOR2 from yeast led to the identification of two distinct TOR protein complexes, TORC1 and TORC2, which account for the differential sensitivity of TOR signaling to rapamycin (Loewith et al., 2002).”
mTOR Is Essential for Growth and Proliferation in Early Mouse Embryos and Embryonic Stem Cells (2004, background): “The recent discoveries of a 150-kDa binding partner of mTOR, named raptor (regulatory-associated protein of mTOR) (14, 27), and its Saccharomyces cerevisiae ortholog, Kog1p (30), have provided new insights about how mTOR regulates p70S6K1 and 4E-BP1 phosphorylation; it has been proposed that raptor ”
Defining the role of mTOR in cancer. (2007, background): “lst8 null budding yeast and Dictyostelium cells are also phenotypically more similar to cells deleted for TORC2-specific components (Lee et al., 2005; Loewith et al., 2002).”
Ablation in mice of the mTORC components raptor, rictor, or mLST8 reveals that mTORC2 is required for signaling to Akt-FOXO and PKCalpha, but not S6K1. (2006, background): “mTORC1 is thought to be a nutrient- and rapamycin-sensitive complex, and raptor is thought to be a key regulator of the nutrient-sensitive mTOR response (Hara et al., 2002; Kim et al., 2002; Loewith et al., 2002).”
TSC2 integrates Wnt and energy signals via a coordinated phosphorylation by AMPK and GSK3 to regulate cell growth. (2006, background): “Two distinct TOR complexes, TORC1 and TORC2, have been characterized (Loewith et al., 2002; Wullschleger et al., 2006).”
Upstream and downstream of mTOR. (2004, background): “In contrast to the data reported for yeast TOR (Loewith et al. 2002), rapamycin disrupts the mTOR–Raptor interaction (Kim et al. 2002; Oshiro et al. 2004), thereby preventing the ability of mTOR to phosphorylate S6K and 4E-BP.”
An Overview of the Molecular Mechanism of Autophagy (2009, background): “Tor forms two functionally distinct protein complexes, Tor complex 1 and 2 (TORC1 and TORC2) (Loewith et al. 2002), and TORC1 has the primary role in regulating autophagy.”