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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

Lookup NU author(s): Piero Dalle Pezze, Dr Daryl Shanley


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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 Ser(2481) 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.

Publication metadata

Author(s): Dalle Pezze P, Sonntag AG, Shanley DP, Thedieck K

Publication type: Letter

Publication status: Published

Journal: Science Signaling

Year: 2012

Volume: 5

Issue: 232

Pages: lc4

Print publication date: 10/07/2012

ISSN (print): 1945-0877

ISSN (electronic): 1937-9145



DOI: 10.1126/scisignal.2003224