IndraLab

Statements

RPS6KB1 inhibits IRS1. 10 / 67
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"Further downstream, mTOR phosphorylates p70 S6 kinase (T389), a regulator of Ribosomal Protein S6 (RPS6) responsible for mRNA translation, and has been proposed to signal via 14-3-3 (tyrosine 3-monooxygenase), a required protein in Raf signaling, to inhibit IRS-1 in a negative feedback loop XREF_BIBR."
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"Therefore, S6K1 is unlikely to trigger IRS-1 degradation under physiological conditions like persistent insulin and IGF stimuli, although S6K1 mediates a negative feedback in ways other than IRS-1 deg[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"Mechanistically, S6K1 inactivates IRS-1 through phosphorylation of the serine (S) residues 307 and 1101, which leads to negative feedback to the PI3K/mTOR pathway."
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"( 4 ) S6K1 inhibits IRS-1 , leading to subsequent ERK2 inhibition and consequent downregulation of S6K1 ."
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"In particular, feedback inhibition of insulin receptor substrate 1 (IRS1) by the kinase p70S6K was predicted to confer resistance to EGFR inhibition, suggesting that disrupting this feedback may restore sensitivity to EGFR inhibitors in colorectal cancer cells."
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"The mTORC1 substrate p70S6 kinase 1 (S6K1) is involved in the regulation of protein synthesis and the growth of cell size, and active S6K1 inhibits IRS1 in a negative feedback loop [ xref ]."
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"The persistent activity of S6K1 (mTORC1_S6K1 in the model) is known to negatively regulate the upstream insulin receptor substrate 1 (noted IRS1_PIK3CA in the model; Laplante & Sabatini, 2012)."
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"The phosphorylation of S6K1 inactivates IRS-1 which is required for insulin signaling through PI3K."
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"A negative feedback loop has been described, whereby mTOR and S6K1 activation attenuates PI3K signaling by suppressing insulin receptor substrate-1 (IRS1) function, a mediator of insulin receptor- dependent activation of PI3K."
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"There were also positive correlations between interventions in the insulin signalling pathway, particularly betweenIrs1 −/− andRps6kb1 −/− mutants, which is interesting considering that Rps6kb1 directly phosphorylates and inhibits Irs1 ( xref )."
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Kinase-active RPS6KB1 inhibits IRS1. 1 / 1
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"S6K was shown to directly phosphorylate IRS-1 to inhibit phosphatidylinositol-3-kinase (PI3K) and Akt activation (Harrington ete al, 2004)."
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