Feedback, Crosstalk and Competition: Ingredients for Emergent Non-Linear Behaviour in the PI3K/mTOR Signalling Network

Ghomlaghi, Milad; Hart, Anthony; Hoang, Nhan; Shin, Sungyoung; Nguyen, Lan K.

doi:10.3390/ijms22136944

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Feedback, Crosstalk and Competition: Ingredients for Emergent Non-Linear Behaviour in the PI3K/mTOR Signalling Network

by

Milad Ghomlaghi

^1,2,

Anthony Hart

^1,2,

Nhan Hoang

¹,

Sungyoung Shin

^1,2

and

Lan K. Nguyen

^1,2,*

¹

Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Clayton, VIC 3800, Australia

²

Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia

^*

Author to whom correspondence should be addressed.

Int. J. Mol. Sci. 2021, 22(13), 6944; https://doi.org/10.3390/ijms22136944

Submission received: 14 May 2021 / Revised: 20 June 2021 / Accepted: 23 June 2021 / Published: 28 June 2021

(This article belongs to the Special Issue mTOR Signaling: New Insights into Cancer, Cardiovascular Diseases, Diabetes and Aging)

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Abstract

The PI3K/mTOR signalling pathway plays a central role in the governing of cell growth, survival and metabolism. As such, it must integrate and decode information from both external and internal sources to guide efficient decision-making by the cell. To facilitate this, the pathway has evolved an intricate web of complex regulatory mechanisms and elaborate crosstalk with neighbouring signalling pathways, making it a highly non-linear system. Here, we describe the mechanistic biological details that underpin these regulatory mechanisms, covering a multitude of negative and positive feedback loops, feed-forward loops, competing protein interactions, and crosstalk with major signalling pathways. Further, we highlight the non-linear and dynamic network behaviours that arise from these regulations, uncovered through computational and experimental studies. Given the pivotal role of the PI3K/mTOR network in cellular homeostasis and its frequent dysregulation in pathologies including cancer and diabetes, a coherent and systems-level understanding of the complex regulation and consequential dynamic signalling behaviours within this network is imperative for advancing biology and development of new therapeutic approaches.

Keywords: PI3K/mTOR signalling; feedback loop; crosstalk; nonlinear dynamics; cancer

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MDPI and ACS Style

Ghomlaghi, M.; Hart, A.; Hoang, N.; Shin, S.; Nguyen, L.K. Feedback, Crosstalk and Competition: Ingredients for Emergent Non-Linear Behaviour in the PI3K/mTOR Signalling Network. Int. J. Mol. Sci. 2021, 22, 6944. https://doi.org/10.3390/ijms22136944

AMA Style

Ghomlaghi M, Hart A, Hoang N, Shin S, Nguyen LK. Feedback, Crosstalk and Competition: Ingredients for Emergent Non-Linear Behaviour in the PI3K/mTOR Signalling Network. International Journal of Molecular Sciences. 2021; 22(13):6944. https://doi.org/10.3390/ijms22136944

Chicago/Turabian Style

Ghomlaghi, Milad, Anthony Hart, Nhan Hoang, Sungyoung Shin, and Lan K. Nguyen. 2021. "Feedback, Crosstalk and Competition: Ingredients for Emergent Non-Linear Behaviour in the PI3K/mTOR Signalling Network" International Journal of Molecular Sciences 22, no. 13: 6944. https://doi.org/10.3390/ijms22136944

APA Style

Ghomlaghi, M., Hart, A., Hoang, N., Shin, S., & Nguyen, L. K. (2021). Feedback, Crosstalk and Competition: Ingredients for Emergent Non-Linear Behaviour in the PI3K/mTOR Signalling Network. International Journal of Molecular Sciences, 22(13), 6944. https://doi.org/10.3390/ijms22136944

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

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Feedback, Crosstalk and Competition: Ingredients for Emergent Non-Linear Behaviour in the PI3K/mTOR Signalling Network

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