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


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 Ca(2+)/calmodulin-dependent protein kinase kinase beta (CaMKKbeta). 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.

SEEK ID: https://fairdomhub.org/publications/390

PubMed ID: 27869123

Projects: PoLiMeR - Polymers in the Liver: Metabolism and Regulation

Publication type: Journal

Journal: Nat Commun

Citation: Nat Commun. 2016 Nov 21;7:13254. doi: 10.1038/ncomms13254.

Date Published: 21st Nov 2016

Registered Mode: Not specified

Authors: P. Dalle Pezze, S. Ruf, A. G. Sonntag, M. Langelaar-Makkinje, P. Hall, A. M. Heberle, P. Razquin Navas, K. van Eunen, R. C. Tolle, J. J. Schwarz, H. Wiese, B. Warscheid, J. Deitersen, B. Stork, E. Fassler, S. Schauble, U. Hahn, P. Horvatovich, D. P. Shanley, K. Thedieck

help Submitter

Views: 1855

Created: 10th Jan 2019 at 13:45

Last updated: 28th Jul 2020 at 18:41

help Tags

This item has not yet been tagged.

help Attributions


Powered by
Copyright © 2008 - 2022 The University of Manchester and HITS gGmbH

By continuing to use this site you agree to the use of cookies