Inappropriate activation of the TSC/Rheb/mTOR/S6K cassette induces IRS1/2 depletion, insulin resistance, and cell survival deficiencies.

By O. Shah, Zhiyong Wang, T. Hunter. Current Biology, 2004

821 citations recorded by the source corpus.

Subfields: Molecular Biology, Physiology

View Paper: https://www.semanticscholar.org/paper/1d646b807fdb4ad30d5bd5e3aff0637eb110de9b

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Citations in the corpus

Malignant astrocytic glioma: genetics, biology, and paths to treatment. (2007, background): “…substrates S6K1 and 4E-BP1, revealed the existence of a negative feedback loop, whereby inhibitory phosphorylation of the insulin receptor substrate (IRS-1) by S6K1 causes a reduction in Akt activation (Harrington et al. 2004; Shah et al. 2004; Riemenschneider et al. 2006; Shah and Hunter 2006).”
Regulation of insulin sensitivity by serine/threonine phosphorylation of insulin receptor substrate proteins IRS1 and IRS2 (2012, background): “It can now be appreciated that feedback S/T phosphorylation of IRS by mTORC1 and/or S6K1 underlies their disappearance during persistent insulin stimulation [49, 50].”
Dysregulation of the TSC-mTOR pathway in human disease (2004, background): “Several recent studies indicate that this negative feedback occurs by S6K-mediated downregulation of insulin receptor substrate activit”
The Lin28/let-7 axis regulates glucose metabolism (2011, background): “Conversely, TSC1-2 promotes insulin-PI3K signaling by suppressing mTOR signaling (Harrington et al., 2004; Shah et al., 2004).”
Rapamycin passes the torch: a new generation of mTOR inhibitors (2011, background): “mTORC1, via S6K phosphorylating insulin receptor substrate 1 (IRS1), can dampen upstream insulin signallin”
PRAS40 is an insulin-regulated inhibitor of the mTORC1 protein kinase. (2007, background): “Substantial evidence (Harrington et al., 2004; Shah et al., 2004) indicates that hyperactive mTORC1 signaling downregulates the insulin/PI3K pathway so that 904 Molecular Cell 25, 903–915, March 23, 2007 ª2007 Elsevier TSC2 null MEFs are in a state equivalent to insulin deprivation.”
LKB1 and AMPK control of mTOR signalling and growth (2009, background): “…hyperlipidaemia and hyperinsulinaemia in the circulation is chronic hyperactivation of the mTORC1 complex, and that mTORC1 and its downstream effector S6K1 both directly phosphorylate the IRS family of scaffolds leading to their targeted degradation (Harrington et al. 2004, Shah et al. 2004).”