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

Article Details

Citation

Chaneton B, Hillmann P, Zheng L, Martin AC, Maddocks OD, Chokkathukalam A, Coyle JE, Jankevics A, Holding FP, Vousden KH, Frezza C, O'Reilly M, Gottlieb E

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

Nature. 2012 Nov 15;491(7424):458-62. doi: 10.1038/nature11540. Epub 2012 Oct 14.

PubMed ID
23064226 [ View in PubMed
]
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.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
Pyruvate kinase PKMP14618Details