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Sci. Signal., 10 July 2012
Vol. 5, Issue 232, p. lc4
[DOI: 10.1126/scisignal.2003224]

LETTERS

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

Piero Dalle Pezze1,2*, Annika G. Sonntag3*, Daryl P. Shanley1,2§, and Kathrin Thedieck3,4,5§

1 Institute for Ageing and Health, Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne NE4 5PL, UK.
2 Centre for Integrated Systems Biology of Ageing and Nutrition, Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne NE4 5PL, UK.
3 Bioinformatics and Molecular Genetics (Faculty of Biology), Albert-Ludwigs-Universität Freiburg, 79104 Freiburg, Germany.
4 BIOSS Centre for Biological Signalling Studies, Albert-Ludwigs-Universität Freiburg, 79104 Freiburg, Germany.
5 Center for Systems Biology (ZBSA), Albert-Ludwigs-Universität Freiburg, 79104 Freiburg, Germany.

* These authors contributed equally to this work.

Abstract: 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.

§ Corresponding author. E-mail: daryl.shanley{at}newcastle.ac.uk (D.P.S.); kathrin.thedieck{at}biologie.uni-freiburg.de (K.T.)

Citation: P. Dalle Pezze, A. G. Sonntag, D. P. Shanley, K. Thedieck, 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. Sci. Signal. 5, lc4 (2012).

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