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  Pyruvate kinase is a dosage-dependent regulator of cellular amino acid homeostasis

Bluemlein, K., Glückmann, M., Grüning, N.-M., Feichtinger, R., Krueger, A., Wamelink6, M., et al. (2012). Pyruvate kinase is a dosage-dependent regulator of cellular amino acid homeostasis. Oncotarget, 3(11), 1356-1356.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-000E-B8A0-A Version Permalink: http://hdl.handle.net/11858/00-001M-0000-000E-B8A1-8
Genre: Journal Article

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2012
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© Bluemlein et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

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 Creators:
Bluemlein, Katharina1, Author              
Glückmann, Matthias2, Author
Grüning, Nana-Maria1, Author              
Feichtinger, René 3, Author
Krueger, Antje1, Author              
Wamelink6,, Mirjam4, Author
Lehrach, Hans1, Author              
Tate, Stephan5, Author
Neureiter, Daniel6, Author
Kofler, Barbara3, Author
Ralser, Markus1, Author              
Affiliations:
1Dept. of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society, Ihnestr. 63-74, Berlin, Germany, ou_1433550              
2AB SCIEX, Landwehrstrasse, Darmstadt, Germany, ou_persistent22              
3Research Program for Receptor Biochemistry and Tumor Metabolism, Department of Pediatrics, Paracelsus Medical University, University Hospital Salzburg, Salzburg, Austria, ou_persistent22              
4VU University Medical Center Amsterdam, Amsterdam, The Netherlands, ou_persistent22              
5AB SCIEX, Concord, Ontario, Canada, ou_persistent22              
6Institute of Pathology, Paracelsus Medical University, University Hospital Salzburg, Salzburg, Austria, ou_persistent22              

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Free keywords: cancer metabolism, pyruvate kinase, proteomics, amino acid profile
 Abstract: The glycolytic enzyme pyruvate kinase (PK) is required for cancer development, and has been implicated in the metabolic transition from oxidative to fermentative metabolism, the Warburg effect. However, the global metabolic response that follows changes in PK activity is not yet fully understood. Using shotgun proteomics, we identified 31 yeast proteins that were regulated in a PK-dependent manner. Selective reaction monitoring confirmed that their expression was dependent on PK isoform, level and activity. Most of the PK targets were amino acid metabolizing enzymes or factors of protein translation, indicating that PK plays a global regulatory role in biosynthethic amino acid metabolism. Indeed, we found strongly altered amino acid profiles when PK levels were changed. Low PK levels increased the cellular glutamine and glutamate concentrations, but decreased the levels of seven amino acids including serine and histidine. To test for evolutionary conservation of this PK function, we quantified orthologues of the identified PK targets in thyroid follicular adenoma, a tumor characterized by high PK levels and low respiratory activity. Aminopeptidase AAP-1 and serine hydroxymethyltransferase SHMT1 both showed PKM2- concentration dependence, and were upregulated in the tumor. Thus, PK expression levels and activity were important for maintaining cellular amino acid homeostasis. Mediating between energy production, ROS clearance and amino acid biosynthesis, PK thus plays a central regulatory role in the metabolism of proliferating cells.

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Language(s): eng - English
 Dates: 2012-11-012012-08-292012-10-302012-11-01
 Publication Status: Published in print
 Pages: -
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 Table of Contents: -
 Rev. Method: -
 Identifiers: ISSN: 1949-2553
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Title: Oncotarget
Source Genre: Journal
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Publ. Info: New York : Albany, N.Y. : Impact Journals
Pages: - Volume / Issue: 3 (11) Sequence Number: - Start / End Page: 1356 - 1356 Identifier: -