Akt regulates growth by directly phosphorylating Tsc2

By Christopher Potter, Laura Pedraza, Tian Xu. Nature Cell Biology, 2002

1,039 citations recorded by the source corpus.

Subfields: Molecular Biology, Physiology

View Paper: https://www.semanticscholar.org/paper/9b15463e1486f33a57c488586879d30ccb16919e

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Citations in the corpus

Regulation of the mTOR complex 1 pathway by nutrients, growth factors, and stress (2010, background): “Akt, along with other kinases downstream of growth factor signaling, such as MAPK and p90 RSK1, phosphorylates TSC2 (Ballif et al., 2005; Li et al., 2003; Potter et al., 2002; Roux et al., 2004; Tee et al., 2003a).”
TSC2 mediates cellular energy response to control cell growth and survival. (2003, positive): “In response to energy starvastudies from several groups have demonstrated that tion, the TSC2 / cells show a defective response in S6K TSC2 is a direct target of Akt (Dan et al., 2002; Inoki et dephosphorylation. Furthermore, the energy starvational., 2002; Manning et al., 2002; Potter et al., 2002)”
Regulation of TORC1 by Rag GTPases in nutrient response (2008, background): “For example, growth factors activate TORC1 partly through phosphatidylinositol-3-kinase (PI(3)K), Akt, TSC1/TSC2 and Rhe”
Upstream and downstream of mTOR. (2004, background): “TSC1 and TSC2 interact through their N termini and appear to function as a heterodimer because overexpression of Drosophila TSC1 or TSC2 alone does not elicit a phenotype, whereas overexpression of both dramatically slows cell growth (Gao and Pan 2001; Potter et al. 2001; Tapon et al. 2001).”
A complex interplay between Akt, TSC2, and the two mTOR complexes (2009, background): “In response to growth factors, Akt directly phosphorylates TSC2 on 4 or 5 distinct residues [17,18], two of which (Ser-939 and Thr-1462 on full-length human TSC2) are conserved and phosphorylated in Drosophila TSC2 [19].”
Autophagy in metazoans: cell survival in the land of plenty (2005, background): “In the presence of growth factors, Akt-dependent TSC2 phosphorylation disrupts the complex and relieves mTOR repressio”
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 TSC1-2 tumor suppressor controls insulin–PI3K signaling via regulation of IRS proteins (2004, background): “Tuberin phosphorylation has been suggested to negatively regulate the TSC1-2 protein complex, allowing activation of S6K and cell growth (Potter et al., 2002).”
TOR signalling in bugs, brain and brawn (2003, background): “TSC1 and TSC2 have a negative effect on TOR signalling, whereas all of the other TOR-binding proteins that have been described above seem to have a positive effect (see below”
mTOR signaling in growth control and disease (2012, positive): “…protein kinase B (Akt/PKB), extracellular-signal-regulated kinase 1/2 (ERK1/2), and ribosomal S6 kinase (RSK1)—directly phosphorylate the TSC1/TSC2 complex to inactivate it and thus activate mTORC1 (Inoki et al., 2002; Ma et al., 2005; Manning et al., 2002; Potter et al., 2002; Roux et al., 2004).”
Rheb promotes cell growth as a component of the insulin/TOR signalling network (2003, background): “Tsc1–Tsc2 is a phosphorylation target of protein kinase B (PKB”
Regulation of mTORC1 and its impact on gene expression at a glance (2013, background): “…et al., 2007), and (2) phosphorylating and inactivating the tuberous sclerosis complex (TSC), a protein complex composed of TSC1 (also known as hamartin), TSC2 (also known as tuberin) and TBC1D7 (Dibble et al., 2012; Inoki et al., 2002; Manning et al., 2002; Potter et al., 2002; Roux et al., 2004).”