IndraLab
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"In addition, when mTORC1 is activated, S6K1 could directly phosphorylate Insulin receptor substrate 1 (IRS1; S307 and S636 and S639) and promote its degradation, which subsequently blunts phosphoinositide 3-kinase (PI3K)-AKT activation and its downstream effects such as glucose uptake and glycogen accumulation."
"Nevertheless, s6k1-deficient mice remain sensitive to insulin owing to the apparent loss of a negative feedback loop from s6k1 to insulin receptor substrate 1 (irs1), which blunts s307 and s636/s639 phosphorylation; thus under conditions of nutrient satiation s6k1 negatively regulatesinsulin."
"In this report, we identified insulin receptor substrate 1 (IRS-1), a critical mediator of the insulin/insulin-like growth factor 1 signaling, as a proteolytic target of the CUL7 E3 ligase in a manner that depends on mammalian target of rapamycin and the p70 S6 kinase activities.Elimination of phosphorylation at S307/S312/S527/S636/S639 renders V5-IRS-1 partially resistant to degradation by Fbw8"