A Dynamic Network Model of mTOR Signaling Reveals TSC-Independent mTORC2 Regulation

Piero Dalle Pezze, Annika G. Sonntag, Antje Thien, Mirja T. Prentzell, Markus Gödel, Sven Fischer, Elke Neumann-Haefelin, Tobias B. Huber, Ralf Baumeister, Daryl P. Shanley,* Kathrin Thedieck*

*To whom correspondence should be addressed. E-mail: kathrin.thedieck{at}biologie.uni-freiburg.de (K.T.); daryl.shanley{at}newcastle.ac.uk (D.P.S.)

This PDF file includes:

• Fig. S1. Extended graphical model of the mammalian TOR network.
• Fig. S2. A linear relationship between Western blot signals and protein concentrations.
• Fig. S3. Phases of the calibration process.
• Fig. S4. Details of a calibration phase.
• Fig. S5. Identifiability analysis for the general model.
• Fig. S6. Sensitivity analysis for the general model.
• Fig. S7. Comparison between the simulated and experimental time courses for hypotheses 1, 2, and 3 for readouts of the mTOR network.
• Fig. S8. Identifiability analysis for hypothesis 1: TSC1-TSC2–dependent hypothesis mTORC2 regulation.
• Fig. S9. Sensitivity analysis for hypothesis 1: TSC1-TSC2–dependent hypothesis mTORC2 regulation.
• Fig. S10. Identifiability analysis for hypothesis 2: NFL-mTORC2 regulation.
• Fig. S11. Sensitivity analysis for hypothesis 2: NFL-mTORC2 regulation.
• Fig. S12. Identifiability analysis for hypothesis 3: PI3K-independent mTORC2 regulation.
• Fig. S13. Sensitivity analysis for hypothesis 3: PI3K-independent mTORC2 regulation.
• Fig. S14. The influence of perturbations of TSC1-TSC2, mTORC1, and PI3K on the phosphorylation of Akt-T³⁰⁸ for the three hypotheses.
• Fig. S15. The influence of perturbations of TSC1-TSC2, mTORC1, and PI3K on the phosphorylation of p70-S6K-T³⁸⁹ for the three hypotheses.
• Fig. S16. Simulation and perturbations for the new network structure based on hypothesis 4: PI3K-dependent, NFL-independent regulation of mTORC2.
• Fig. S17. Identifiability analysis for hypothesis 4: PI3K-dependent, NFL-independent regulation of mTORC2.
• Fig. S18. Sensitivity analysis for hypothesis 4: PI3K-dependent, NFL-independent regulation of mTORC2.
• Table S1. Ordinary differential equations of the general model and the models representing hypotheses, 1, 2, and 3 for mTORC2 activation.
• Table S2. Parameter values of the general model.
• Table S3. Parameter values of hypotheses 1, 2, and 3.
• Table S4. Summary of model goodness of fit.
• Legends for Models S1 to S6.
  

[Download PDF]

Technical Details

Format: Adobe Acrobat PDF

Size: 7.58 MB

Other Supplementary Material for this manuscript includes the following:

• Models S1 to S6 (.xml format).

[Download Models S1 to S6 (Compressed)]

Technical Details

Format: XML. Files are packaged as a compressed archive, in *.zip format; users should download the compressed file to their machine and decompress the file on their local hard drive, using the instructions below.

Size: 47 KB (compressed); 788 KB (decompressed)

Instructions for downloading and decompressing files:

1. Create a temporary folder on your machine's hard drive.
2. Save the compressed archive to the temporary folder you created, using the links above.
3. Decompress the compressed file in the temporary folder using decompression software such as WinZip (Windows; www.winzip.com) or StuffIt Expander (Windows and Mac; www.stuffit.com).

© 2012 American Association for the Advancement of Science