TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling

By K. Inoki, Yong Li, Tian Zhu, Jun Wu, K. Guan. Nature Cell Biology, 2002

3,197 citations recorded by the source corpus.

Subfields: Molecular Biology, Physiology

View Paper: https://www.semanticscholar.org/paper/3e919374fc6557ffcaaf801749b0ef09e9471562

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Citations in the corpus

Regulation of mTOR function in response to hypoxia by REDD1 and the TSC1/TSC2 tumor suppressor complex. (2004, background): “Akt is a serine/threonine kinase that phosphorylates many effectors including Tsc2 (Dan et al. 2002; Inoki et al. 2002; Manning et al. 2002; Potter et al. 2002).”
The RAS/RAF/MEK/ERK and the PI3K/AKT signalling pathways: role in cancer pathogenesis and implications for therapeutic approaches (2012, background): “Activated rheb stimulates the activation of mTORC1, resulting in the phosphorylation of p70 ribosomal protein S6 kinase 1 (S6K) and the eukaryotic initiation factor 4E binding protein 1 (4E-BP1), ultimately leading to increased protein synthesis (Figure 1) [12,21].”
AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1 (2011, neutral): “To further evaluate a role for mTORC1 in Ulk1 phosphorylation, we examined Ulk1 Ser 757 phosphorylation in the Tsc1 −/− MEF, which has an elevated mTORC1 activit”
mTOR: from growth signal integration to cancer, diabetes and ageing (2010, background): “In turn, Akt phosphorylates TSC2, a large protein that, together with TSC1 (also known as hamartin), forms the TSC1–TSC2 comple”
Adiponectin, a Therapeutic Target for Obesity, Diabetes, and Endothelial Dysfunction (2017, background): “Proteiogenic effect of insulin is mediated in part by activation of the target of rapamycin TOR pathway via phosphorylation of TSC2, whereas AMPK activation causes phosphorylation of different sites on TSC2 and inhibits TOR [51,52].”
The PTEN–PI3K pathway: of feedbacks and cross-talks (2008, background): “On the other hand, a study from our group has recently shown that ERK can also directly phosphorylate TSC2 on Ser664, leading to the inhibition of the complex (Ma et al., 2005a).”
The mTOR Signalling Pathway in Human Cancer (2012, background): “Since TSC1/TSC2 GAP activity is not required for mTORC2 activation, it appears that it is independent of mTORC1 activation and of the negative feedback loop from mTORC1 and S6K1 to the upstream IRS [94].”
mTOR: a pharmacologic target for autophagy regulation. (2015, positive): “It has also been shown that metformin can inhibit mTORC1 in an AMPK-independent manner, possibly via Rag GTPases or REDD1 (112, 113).”
PI3K/AKT/mTOR signaling transduction pathway and targeted therapies in cancer (2023, background): “AKT‑induced phosphorylation on TSC2 hampers the ability of TSC Complex to act as a GAP toward the small GTPase Rheb, endorsing Rheb‑GTP accumulation.”
Mechanisms of activation of the transcription factor Nrf2 by redox stressors, nutrient cues, and energy status and the pathways through which it attenuates degenerative disease (2015, positive): “This suggests that AMPK and GSK-3 cooperatively inhibit mTORC1, insofar as the ability of GSK-3 to inhibit mTORC1 is enhanced when AMPK primes TSC1/2 for phosphorylation [317].”