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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...
Autores principales: | , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2016
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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 |
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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 |
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