Lopez-Caamal, Fernando, García, Míriam R., Middleton, Richard H. and Huber, Heinrich J. (2012) Positive Feedback in the AKT/mTOR pathway and its implications for growth signal progression in skeletal muscle cells: An analytical study. Journal of Theoretical Biology, 301. pp. 15-27. ISSN 0022-5193
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Abstract
The IGF-1 mediated AKT/mTOR pathway has been recently proposed
as mediator of skeletal muscle growth and a positive feedback between Akt
and mTOR was suggested to induce homogenous growth signals along the
whole spatial extension of such long cells. Here we develop two biologically
justied approximations which we study under the presence of four dierent
initial conditions that describe dierent paradigms of IGF-1 receptor{induced
Akt/mTOR activation. In rst scenario the activation of the feedback cascade
was assumed to be mild or protein turnover considered to be high. In
turn, in the second scenario the transcriptional regulation was assumed to
maintain dened levels of inactive pro{enzymes. For both scenarios, we were
able to obtain closed{form formulas for growth signal progression in time and
space and found that a localised initial signal maintains its Gaussian shape,
but gets delocalised and exponentially degraded. Importantly, mathematical
treatment of the reaction diusion system revealed that diusion ltered
out high frequencies of spatially periodic initiator signals suggesting that the
muscle cell is robust against
uctuations in spatial receptor expression or activation.
However, neither scenario was consistent with the presence of stably
travelling signal waves. Our study highlights the role of feedback loops in
spatiotemporal signal progression and results can be applied to studies in cell proliferation, cell dierentiation and cell death in other spatially extended
cells.
Item Type: | Article |
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Additional Information: | Preprint version of original published article. The definitive version of this article is available at http://www.sciencedirect.com/ DOI: http://dx.doi.org/10.1016/j.jtbi.2012.01.026 |
Keywords: | AKT/mTOR; Skeletal muscle; Positive feedback; Protein activation; PDE; Analytical solutions; |
Academic Unit: | Faculty of Science and Engineering > Research Institutes > Hamilton Institute |
Item ID: | 3621 |
Depositing User: | Miriam Garcia |
Date Deposited: | 01 May 2012 15:31 |
Journal or Publication Title: | Journal of Theoretical Biology |
Publisher: | Elsevier |
Refereed: | No |
Related URLs: | |
URI: | https://mu.eprints-hosting.org/id/eprint/3621 |
Use Licence: | This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available here |
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