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Polysome Fractionation and Analysis of Mammalian Translatomes on a Genome-wide Scale

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Deconvolution of mTORC2 "in Silico".

Diane C Fingar¹, Ken Inoki

¹Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA. dfingar@umich.edu

Science Signaling

|March 30, 2012

Summary

The mammalian target of rapamycin (mTOR) network regulates cell growth and metabolism. This study clarifies how insulin activates mTORC2 using biochemical methods and computational modeling.

Area of Science:

Molecular Biology
Cell Signaling
Systems Biology

Background:

The protein kinase mTOR is central to cellular processes, forming mTORC1 and mTORC2 complexes.
mTORC1 and mTORC2 differentially regulate cell growth, proliferation, survival, and metabolism.
Dysregulation of mTOR signaling is implicated in diseases like cancer, diabetes, and cardiovascular disease.

Purpose of the Study:

To investigate the intricate insulin-mTOR network.
To elucidate the poorly understood mechanism of insulin-induced mTORC2 activation.

Main Methods:

Combined classic biochemical approaches.
Employed dynamic mathematical modeling in silico.

Main Results:

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Detailed the complex signal transduction network coordinated by mTOR.

Elucidated the activation pathway of mTORC2 by insulin.

Demonstrated differential substrate phosphorylation by mTORC1 and mTORC2.

Conclusions:

Understanding mTOR network circuitry offers insights into disease pathogenesis.
The study provides a clearer picture of insulin's role in activating mTORC2.
Integrated approaches are valuable for dissecting complex signaling networks.