Prolonged rapamycin treatment inhibits mTORC2 assembly and Akt/PKB.

By Dos D. Sarbassov, Siraj M. Ali, Shomit Sengupta, Joon-ho Sheen, Peggy P. Hsu, A. Bagley, Andrew L. Markhard, David M. Sabatini. Molecules and Cells, 2006

2,823 citations recorded by the source corpus.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/ce92f74931160b317440ed5b91929053cac6aed6

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In Molecular Biology

1. David M. Sabatini
2. M. Laplante
3. K. Guan
4. Michael N. Hall
5. B. Manning
6. R. A. Saxton
7. M. Karin
8. J. Blenis

Citations in the corpus

• The TSC1-TSC2 complex: a molecular switchboard controlling cell growth. (2008, background): “However, prolonged rapamycin treatment affects mammalian TORC2 (mTORC2) assembly and can block mTORC2 function in some cells [36].”
• Targeting phosphoinositide 3-kinase: moving towards therapy. (2008, background): “mTOR “knock-out” mice die shortly after implantation due to defects in trophoblast differentiation and embryonic stem cells proliferation [166,167].”
• Mechanisms of Life Span Extension by Rapamycin in the Fruit Fly Drosophila melanogaster (2010, background): “Thus, there is a complex cross-wiring between the two signaling pathways, the outcome of which may depend on cell type and on the intensity and duration of the signal (Sarbassov et al., 2006).”
• An emerging role of mTOR in lipid biosynthesis (2009, neutral): “Most of the studies linking mTOR signaling to adipogenesis were based on long-term rapamycin treatments, an experimental condition that can also lead to mTORC2 inhibition [30].”
• The mammalian Target of Rapamycin (mTOR) regulates T helper cell differentiation through the selective activation of mTORC1 and mTORC2 signaling (2011, background): “Biochemical analysis of T cells showed that rapamycin inhibited mTORC2 activit”
• Rapamycin passes the torch: a new generation of mTOR inhibitors (2011, background): “It is generally insensitive to inhibition by rapamycin, although in certain cell types, mTORC2 may show sensitivity after prolonged rapamycin treatmen”
• p53 target genes sestrin1 and sestrin2 connect genotoxic stress and mTOR signaling. (2008, positive): “Rapamycin, an inhibitor of cell growth, rapidly inhibits mTORC1 through interaction with FKBP12, but after a while, it may also inhibit mTORC2 (Sarbassov et al., 2006). mTORC1 activity is positively regulated by growth factors through the insulin/insulin-like growth factor (IGF1)-phosphoinositide-3…”
• Translational control of long-lasting synaptic plasticity and memory. (2009, positive): “For example, inactivation of Dicer in forebrain, Purkinje, and dopaminergic neurons results in microcephaly, progressive neurodegeneration , and increased apoptosis and neurodegeneration, respectively (Davis et al., 2008; Hebert and De Strooper, 2007; Kim et al., 2007; Schaefer et al., 2007).”
• 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): “This is consistent with previous observations that Akt/PKB mobility is sensitive to the charge associated with its phosphorylation sites (Alessi et al., 1996; Sarbassov et al., 2006).”
• Regulation of the mTOR complex 1 pathway by nutrients, growth factors, and stress (2010, background): “In these cells, disassociation and/or assembly of mTORC2 occurs in a manner that allows rapamycin-FKBP12 to bind free mTOR, which interferes with assembly of mTORC2 components (Sarbassov et al., 2006).”
• mTOR signaling in growth control and disease (2012, positive): “However, the situation turns out to be much more complex as long term treatment with rapamycin reduces mTORC2 signaling in some, but not all, cell types and does so by suppressing mTORC2 assembly (Phung et al., 2006; Sarbassov et al., 2006).”