On the appropriateness of antibody selection to estimate mTORC1 activity.

The authors chose to assess mTORC1 activity by utilizing two targets, mTOR Ser SP 2448 sp and rpS6 Ser SP 235/236 sp phosphorylation which are thought to directly reflect mTORC1 activity. Firstly, mTOR Ser SP 2448 sp phosphorylation is not a reliable marker of mTORC1 activity.[2] mTOR Ser SP 2448 sp is actually a target of p70S6K, as part of a feedback mechanism.[[3]] Importantly, this feedback mechanism is more likely to be indicative of mTORC1 inhibition rather than activation.[2] While in some contexts, mTOR Ser SP 2448 sp phosphorylation may parallel changes in mTORC1 activity since it is a target of its downstream p70S6K; that is not always the case.[2] Therefore, this phosphorylation event by itself should not be taken as indicative of mTORC1 activity. As exercise and mechanical cues have long been known to induce RSK phosphorylation,[[8]] the authors were likely measuring the combined effects of both mTORC1 and MAPK pathway activation. [Extracted from the article]