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

被引：494

作者：

Chaneton, Barbara ^{[1
]}

Hillmann, Petra ^{[2
]}

Zheng, Liang ^{[1
]}

Martin, Agnes C. L. ^{[2
]}

Maddocks, Oliver D. K. ^{[1
]}

Chokkathukalam, Achuthanunni ^{[3
]}

Coyle, Joseph E. ^{[2
]}

Jankevics, Andris ^{[3
,4
]}

Holding, Finn P. ^{[2
]}

Vousden, Karen H. ^{[1
]}

Frezza, Christian ^{[1
]}

O'Reilly, Marc ^{[2
]}

Gottlieb, Eyal ^{[1
]}

机构：

[1] Canc Res UK, Beatson Inst Canc Res, Glasgow G61 1BD, Lanark, Scotland

[2] Astex Pharmaceut, Cambridge CB4 0QA, England

[3] Univ Glasgow, Coll Med Vet & Life Sci, Inst Mol Cell & Syst Biol, Glasgow G12 8QQ, Lanark, Scotland

[4] Univ Groningen, Groningen Biomol Sci & Biotechnol Inst, Groningen Bioinformat Ctr, NL-9747 AG Groningen, Netherlands

来源：

NATURE | 2012年 / 491卷 / 7424期

关键词：

MASS-SPECTROMETRY DATA; X-RAY DATA; TUMOR-GROWTH; CANCER; CRYSTALLOGRAPHY; CONTRIBUTES; GLYCOLYSIS; METABOLISM; PATHWAY; QUALITY;

D O I：

10.1038/nature11540

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Cancer cells exhibit several unique metabolic phenotypes that are critical for cell growth and proliferation(1). 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(2). 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.

引用

页码：458 / +

页数：7

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