Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Pezze, Piero Dalle, Ruf, Stefanie, Sonntag, Annika G., Langelaar-Makkinje, Miriam, Hall, Philip, Heberle, Alexander M., Navas, Patricia Razquin, van Eunen, Karen, Tölle, Regine C., Schwarz, Jennifer J., Wiese, Heike, Warscheid, Bettina, Deitersen, Jana, Stork, Björn, Fäßler, Erik, Schäuble, Sascha, Hahn, Udo, Horvatovich, Peter, Shanley, Daryl P., Thedieck, Kathrin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5121333/
https://www.ncbi.nlm.nih.gov/pubmed/27869123
http://dx.doi.org/10.1038/ncomms13254
_version_ 1782469389089505280
author Pezze, Piero Dalle
Ruf, Stefanie
Sonntag, Annika G.
Langelaar-Makkinje, Miriam
Hall, Philip
Heberle, Alexander M.
Navas, Patricia Razquin
van Eunen, Karen
Tölle, Regine C.
Schwarz, Jennifer J.
Wiese, Heike
Warscheid, Bettina
Deitersen, Jana
Stork, Björn
Fäßler, Erik
Schäuble, Sascha
Hahn, Udo
Horvatovich, Peter
Shanley, Daryl P.
Thedieck, Kathrin
author_facet Pezze, Piero Dalle
Ruf, Stefanie
Sonntag, Annika G.
Langelaar-Makkinje, Miriam
Hall, Philip
Heberle, Alexander M.
Navas, Patricia Razquin
van Eunen, Karen
Tölle, Regine C.
Schwarz, Jennifer J.
Wiese, Heike
Warscheid, Bettina
Deitersen, Jana
Stork, Björn
Fäßler, Erik
Schäuble, Sascha
Hahn, Udo
Horvatovich, Peter
Shanley, Daryl P.
Thedieck, Kathrin
author_sort Pezze, Piero Dalle
collection PubMed
description 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 β (CaMKKβ). 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.
format Online
Article
Text
id pubmed-5121333
institution National Center for Biotechnology Information
language English
publishDate 2016
publisher Nature Publishing Group
record_format MEDLINE/PubMed
spelling pubmed-51213332016-12-02 A systems study reveals concurrent activation of AMPK and mTOR by amino acids Pezze, Piero Dalle Ruf, Stefanie Sonntag, Annika G. Langelaar-Makkinje, Miriam Hall, Philip Heberle, Alexander M. Navas, Patricia Razquin van Eunen, Karen Tölle, Regine C. Schwarz, Jennifer J. Wiese, Heike Warscheid, Bettina Deitersen, Jana Stork, Björn Fäßler, Erik Schäuble, Sascha Hahn, Udo Horvatovich, Peter Shanley, Daryl P. Thedieck, Kathrin Nat Commun Article 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 β (CaMKKβ). 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. Nature Publishing Group 2016-11-21 /pmc/articles/PMC5121333/ /pubmed/27869123 http://dx.doi.org/10.1038/ncomms13254 Text en Copyright © 2016, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Pezze, Piero Dalle
Ruf, Stefanie
Sonntag, Annika G.
Langelaar-Makkinje, Miriam
Hall, Philip
Heberle, Alexander M.
Navas, Patricia Razquin
van Eunen, Karen
Tölle, Regine C.
Schwarz, Jennifer J.
Wiese, Heike
Warscheid, Bettina
Deitersen, Jana
Stork, Björn
Fäßler, Erik
Schäuble, Sascha
Hahn, Udo
Horvatovich, Peter
Shanley, Daryl P.
Thedieck, Kathrin
A systems study reveals concurrent activation of AMPK and mTOR by amino acids
title A systems study reveals concurrent activation of AMPK and mTOR by amino acids
title_full A systems study reveals concurrent activation of AMPK and mTOR by amino acids
title_fullStr A systems study reveals concurrent activation of AMPK and mTOR by amino acids
title_full_unstemmed A systems study reveals concurrent activation of AMPK and mTOR by amino acids
title_short A systems study reveals concurrent activation of AMPK and mTOR by amino acids
title_sort systems study reveals concurrent activation of ampk and mtor by amino acids
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5121333/
https://www.ncbi.nlm.nih.gov/pubmed/27869123
http://dx.doi.org/10.1038/ncomms13254
work_keys_str_mv AT pezzepierodalle asystemsstudyrevealsconcurrentactivationofampkandmtorbyaminoacids
AT rufstefanie asystemsstudyrevealsconcurrentactivationofampkandmtorbyaminoacids
AT sonntagannikag asystemsstudyrevealsconcurrentactivationofampkandmtorbyaminoacids
AT langelaarmakkinjemiriam asystemsstudyrevealsconcurrentactivationofampkandmtorbyaminoacids
AT hallphilip asystemsstudyrevealsconcurrentactivationofampkandmtorbyaminoacids
AT heberlealexanderm asystemsstudyrevealsconcurrentactivationofampkandmtorbyaminoacids
AT navaspatriciarazquin asystemsstudyrevealsconcurrentactivationofampkandmtorbyaminoacids
AT vaneunenkaren asystemsstudyrevealsconcurrentactivationofampkandmtorbyaminoacids
AT tollereginec asystemsstudyrevealsconcurrentactivationofampkandmtorbyaminoacids
AT schwarzjenniferj asystemsstudyrevealsconcurrentactivationofampkandmtorbyaminoacids
AT wieseheike asystemsstudyrevealsconcurrentactivationofampkandmtorbyaminoacids
AT warscheidbettina asystemsstudyrevealsconcurrentactivationofampkandmtorbyaminoacids
AT deitersenjana asystemsstudyrevealsconcurrentactivationofampkandmtorbyaminoacids
AT storkbjorn asystemsstudyrevealsconcurrentactivationofampkandmtorbyaminoacids
AT faßlererik asystemsstudyrevealsconcurrentactivationofampkandmtorbyaminoacids
AT schaublesascha asystemsstudyrevealsconcurrentactivationofampkandmtorbyaminoacids
AT hahnudo asystemsstudyrevealsconcurrentactivationofampkandmtorbyaminoacids
AT horvatovichpeter asystemsstudyrevealsconcurrentactivationofampkandmtorbyaminoacids
AT shanleydarylp asystemsstudyrevealsconcurrentactivationofampkandmtorbyaminoacids
AT thedieckkathrin asystemsstudyrevealsconcurrentactivationofampkandmtorbyaminoacids
AT pezzepierodalle systemsstudyrevealsconcurrentactivationofampkandmtorbyaminoacids
AT rufstefanie systemsstudyrevealsconcurrentactivationofampkandmtorbyaminoacids
AT sonntagannikag systemsstudyrevealsconcurrentactivationofampkandmtorbyaminoacids
AT langelaarmakkinjemiriam systemsstudyrevealsconcurrentactivationofampkandmtorbyaminoacids
AT hallphilip systemsstudyrevealsconcurrentactivationofampkandmtorbyaminoacids
AT heberlealexanderm systemsstudyrevealsconcurrentactivationofampkandmtorbyaminoacids
AT navaspatriciarazquin systemsstudyrevealsconcurrentactivationofampkandmtorbyaminoacids
AT vaneunenkaren systemsstudyrevealsconcurrentactivationofampkandmtorbyaminoacids
AT tollereginec systemsstudyrevealsconcurrentactivationofampkandmtorbyaminoacids
AT schwarzjenniferj systemsstudyrevealsconcurrentactivationofampkandmtorbyaminoacids
AT wieseheike systemsstudyrevealsconcurrentactivationofampkandmtorbyaminoacids
AT warscheidbettina systemsstudyrevealsconcurrentactivationofampkandmtorbyaminoacids
AT deitersenjana systemsstudyrevealsconcurrentactivationofampkandmtorbyaminoacids
AT storkbjorn systemsstudyrevealsconcurrentactivationofampkandmtorbyaminoacids
AT faßlererik systemsstudyrevealsconcurrentactivationofampkandmtorbyaminoacids
AT schaublesascha systemsstudyrevealsconcurrentactivationofampkandmtorbyaminoacids
AT hahnudo systemsstudyrevealsconcurrentactivationofampkandmtorbyaminoacids
AT horvatovichpeter systemsstudyrevealsconcurrentactivationofampkandmtorbyaminoacids
AT shanleydarylp systemsstudyrevealsconcurrentactivationofampkandmtorbyaminoacids
AT thedieckkathrin systemsstudyrevealsconcurrentactivationofampkandmtorbyaminoacids