Response to Comment on “A Dynamic Network Model of mTOR Signaling Reveals TSC-Independent mTORC2 Regulation”: Building a Model of the mTOR Signaling Network with a Potentially Faulty Tool

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Sci. Signal.  03 Jul 2012:
DOI: 10.1126/scisignal.2003224


We modeled the mammalian or mechanistic target of rapamycin (mTOR) network and proposed a previously unknown mode of activation of the mTOR-containing complex mTORC2 through a phosphoinositide 3-kinase–dependent and tuberous sclerosis complex–independent mechanism. Manning questions the validity of using the phosphorylation of Ser2481 of mTOR as a specific readout of mTORC2 activity and suggests an in vitro mTORC2 kinase assay as a more appropriate method to parameterize a dynamic mTOR model. We maintain that our computational-experimental approach in combination with careful selection of the readout and cell system is appropriate for studying mTORC2 regulation by insulin.

Full article available 10 July 2012, Vol. 5, Issue 232, pp. lc4