Format

Send to

Choose Destination
Nature. 2012 Nov 15;491(7424):458-462. doi: 10.1038/nature11540. Epub 2012 Oct 14.

Serine is a natural ligand and allosteric activator of pyruvate kinase M2.

Author information

1
Cancer Research UK, The Beatson Institute for Cancer Research, Switchback Road, Glasgow, G61 1BD, Scotland, United Kingdom.
2
Astex Pharmaceuticals, 436 Cambridge Science Park, Milton Road, Cambridge, CB4 0QA, United Kingdom.
3
Institute of Molecular, Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, Joseph Black Building, B3.09, University of Glasgow, Glasgow, G12 8QQ, Scotland, United Kingdom.
4
Groningen Bioinformatics Centre, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Groningen, The Netherlands.
#
Contributed equally

Erratum in

  • Nature. 2013 Apr 18;496(7445):386.

Abstract

Cancer cells exhibit several unique metabolic phenotypes that are critical for cell growth and proliferation. Specifically, they overexpress the M2 isoform of the tightly regulated enzyme pyruvate kinase (PKM2), which controls glycolytic flux, and are highly dependent on de novo biosynthesis of serine and glycine. Here we describe a new rheostat-like mechanistic relationship between PKM2 activity and serine biosynthesis. We show that serine can bind to and activate human PKM2, and that PKM2 activity in cells is reduced in response to serine deprivation. This reduction in PKM2 activity shifts cells to a fuel-efficient mode in which more pyruvate is diverted to the mitochondria and more glucose-derived carbon is channelled into serine biosynthesis to support cell proliferation.

PMID:
23064226
PMCID:
PMC3894725
DOI:
10.1038/nature11540
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center