Toggle Main Menu Toggle Search

Open Access padlockePrints

A systems study reveals concurrent activation of AMPK and mTOR by amino acids

Lookup NU author(s): Philip Hall, Dr Daryl Shanley

Downloads


Licence

This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

Amino acids (aa) are not only building blocks for proteins, but also signalling molecules, with the mammalian target of rapamycin complex 1 (mTORC1) acting as a key mediator. However, little is known about whether aa, independently of mTORC1, activate other kinases of the mTOR signalling network. To delineate aa-stimulated mTOR network dynamics, we here combine a computational-experimental approach with text mining-enhanced quantitative proteomics. We report that AMP-activated protein kinase (AMPK), phosphatidylinositide 3-kinase (PI3K) and mTOR complex 2 (mTORC2) are acutely activated by aa-readdition in an mTORC1-independent manner. AMPK activation by aa is mediated by Ca2+/calmodulin-dependent protein kinase kinase beta (CaMKK beta). In response, AMPK impinges on the autophagy regulators Unc-51-like kinase-1 (ULK1) and c-Jun. AMPK is widely recognized as an mTORC1 antagonist that is activated by starvation. We find that aa acutely activate AMPK concurrently with mTOR. We show that AMPK under aa sufficiency acts to sustain autophagy. This may be required to maintain protein homoeostasis and deliver metabolite intermediates for biosynthetic processes.


Publication metadata

Author(s): Pezze PD, Ruf S, Sonntag AG, Langelaar-Makkinje M, Hall P, Heberle AM, Navas PR, van Eunen K, Tolle RC, Schwarz JJ, Wiese H, Warscheid B, Deitersen J, Stork B, Fassler E, Schauble S, Hahn U, Horvatovich P, Shanley DP, Thedieck K

Publication type: Article

Publication status: Published

Journal: Nature Communications

Year: 2016

Volume: 7

Online publication date: 21/11/2016

Acceptance date: 13/09/2016

Date deposited: 06/01/2017

ISSN (electronic): 2041-1723

Publisher: Nature Publishing Group

URL: http://dx.doi.org/10.1038/ncomms13254

DOI: 10.1038/ncomms13254


Altmetrics

Altmetrics provided by Altmetric


Actions

Find at Newcastle University icon    Link to this publication


Share