Increased insulin signalling can result in rapid cell growth and increased survival owing to a rise in glucose consumption. Soliman et al. studied the role of p66SHC (the p66 isoform of the adaptor protein SHC (SRC homology 2 containing)), a mediator of growth factor signalling, in cell metabolism. By measuring glucose uptake and catabolism in p66SHC-deficient and wild-type cells, and comparing their metabolite profiles, they found that p66SHC inhibits glycolytic metabolism, lipid biosynthesis, amino acid biosynthesis and pyrimidine metabolism. The authors further showed that the effects of p66SHC are partly mediated by the inhibition of mTOR signalling in response to insulin. Their data indicate that p66SHC has a prominent role in inhibiting glycolysis and anabolic metabolism in favour of oxidative respiration.
References
Soliman, M. A. et al. The adaptor protein p66Shc inhibits mTOR-dependent anabolic metabolism. Sci. Signal. 7, ra17 (2014)
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Zlotorynski, E. p66SHC inhibits anabolic metabolism. Nat Rev Mol Cell Biol 15, 222 (2014). https://doi.org/10.1038/nrm3783
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DOI: https://doi.org/10.1038/nrm3783