Tuberous sclerosis complex-1 and -2 gene products function together to inhibit mammalian target of rapamycin (mTOR)-mediated downstream signaling

By Andrew R. Tee, D. Fingar, B. Manning, D. Kwiatkowski, Lewis C. Cantley, J. Blenis. Proceedings of the National Academy of Sciences of the United States of America, 2002

850 citations recorded by the source corpus.

Subfields: Molecular Biology, Physiology

View Paper: https://www.semanticscholar.org/paper/50ced3e181cb003698fd6e97743e38ec3ac9c74f

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

1. David M. Sabatini
2. K. Guan
3. Michael N. Hall
4. B. Manning
5. M. Laplante
6. J. Blenis
7. N. Hay
8. Nahum Sonenberg

In Physiology

1. David M. Sabatini
2. B. Manning
3. K. Guan
4. Michael N. Hall
5. Jingxiang Huang
6. N. Hay
7. K. Inoki
8. J. Blenis

Citations in the corpus

• Multi-compartment microscopic diffusion imaging (2016, background): “These proteins control the activity of the mammalian target of rapamycin (mTOR) kinase, which regulates cell size, proliferation and differentiation (Tee et al., 2002).”
• Phosphoinositides: tiny lipids with giant impact on cell regulation. (2013, background): “Akt/PKB inactivates the TSC1-TSC2 (hamartin-tuberin) complex, which is a critical inhibitory regulator of mTORC1 (491, 697, 1541).”
• The TSC1-TSC2 complex: a molecular switchboard controlling cell growth. (2008, background): “rapamycin-sensitive) phosphorylation of both S6K1 and 4E-BP1 is inhibited by TSC1–TSC2 complex overexpression and is activated in cells lacking the TSC1–TSC2 complex [21,22,25,42–45].”
• Regulation and role of autophagy in mammalian cells. (2004, background): “The activation of PI3K/PKB was shown to relieve the inhibitory effects of the tuberous sclerosis complex (TSC1/TSC2, hamartin/tuberin) on mTOR/p70S6 kinase signaling (Gao et al., 2002; Tee et al., 2002; Inoki, Li, Zhu, Wu, & Guan, 2002; Jaeschke et al., 2002).”
• TOR signalling in bugs, brain and brawn (2003, background): “Genetic evidence in flies and biochemical evidence in mammalian cells indicate that the TSC1–TSC2 complex binds and inhibits TO”
• When Overgrowth Bumps Into Cancer: The PTEN‐Opathies (2013, background): “When stable, the TSC works to inhibit mTOR [Tee et al., 2002].”
• Rheb GTPase is a direct target of TSC2 GAP activity and regulates mTOR signaling. (2003, background): “The RasV12 mutant is known to be resistant to down-regulation by RasGAP (Trahey and McCormick 1987).”
• TSC2 mediates cellular energy response to control cell growth and survival. (2003, background): “The gene products of TSC1 and TSC2 form a the phosphorylation of S6K and 4EBP1 (Goncharova et functional complex and inhibit the phosphorylation of al., 2002; Inoki et al., 2002; Tee et al., 2002).”
• Nutrient sensing and TOR signaling in yeast and mammals (2017, neutral): “…associates with TSC1 and TBC1D7 to form the TSC complex that functions as GAP (GTPase-activating protein) toward lysosomal RHEB (Gao et al , 2002; Kenerson et al , 2002; Kwiatkowski et al , 2002; Onda et al , 2002; Tee et al , 2002; Garami et al , 2003; Inoki et al , 2003a; Dibble et al , 2012).”