2 Matching Annotations
  1. Jul 2018
    1. On 2014 May 14, Jim Woodgett commented:

      Interesting paper but the evidence that the effect is selectively mediated through GSK-3beta is questionable. In support of the contention is that a band of ~45kDa was found (figure 5A) with a phospho-Akt substrate antibody. However, there's another band ~4kDa above it. In figure 6, an inhibitor to GSK-3 was used: "glucose uptake and lactate production were measured in the presence or absence of the Gsk-3β inhibitor SB 216763". This inhibitor is equally effective in blocking the 51kDa isoform, GSK-3alpha (no small molecule inhibitors are isoform selective - I am a scratched record). Moreover, Akt/PKB phosphorylates GSK-3alpha at serine 21 and GSK-3beta at serine 9. As far as I am aware, there are no published data to suggest that Akt differentiates between the two GSK-3 isoforms and since they are ubiquitously expressed, both are very likely phosphorylated and inhibited upon phosphatidylinositol 3' kinase activation. Hence, I'd recommend modifying the title and conclusions to: "Insulin Receptor Substrate-2 Mediated Phosphatidylinositol 3-kinase Signaling Selectively Inhibits Glycogen Synthase Kinase-3 to Regulate Aerobic Glycolysis" as this more accurately reflects the actual experimental data and tools used. This mistake is frequent in the literature (assumptive assignment of effects to GSK-3β). In the majority of cases, the experimental evidence presented does not exclude GSK-3alpha.


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  2. Feb 2018
    1. On 2014 May 14, Jim Woodgett commented:

      Interesting paper but the evidence that the effect is selectively mediated through GSK-3beta is questionable. In support of the contention is that a band of ~45kDa was found (figure 5A) with a phospho-Akt substrate antibody. However, there's another band ~4kDa above it. In figure 6, an inhibitor to GSK-3 was used: "glucose uptake and lactate production were measured in the presence or absence of the Gsk-3β inhibitor SB 216763". This inhibitor is equally effective in blocking the 51kDa isoform, GSK-3alpha (no small molecule inhibitors are isoform selective - I am a scratched record). Moreover, Akt/PKB phosphorylates GSK-3alpha at serine 21 and GSK-3beta at serine 9. As far as I am aware, there are no published data to suggest that Akt differentiates between the two GSK-3 isoforms and since they are ubiquitously expressed, both are very likely phosphorylated and inhibited upon phosphatidylinositol 3' kinase activation. Hence, I'd recommend modifying the title and conclusions to: "Insulin Receptor Substrate-2 Mediated Phosphatidylinositol 3-kinase Signaling Selectively Inhibits Glycogen Synthase Kinase-3 to Regulate Aerobic Glycolysis" as this more accurately reflects the actual experimental data and tools used. This mistake is frequent in the literature (assumptive assignment of effects to GSK-3β). In the majority of cases, the experimental evidence presented does not exclude GSK-3alpha.


      This comment, imported by Hypothesis from PubMed Commons, is licensed under CC BY.