作者
Taro Hitosugi, Sumin Kang, Matthew G Vander Heiden, Tae-Wook Chung, Shannon Elf, Katherine Lythgoe, Shaozhong Dong, Sagar Lonial, Xu Wang, Georgia Z Chen, Jianxin Xie, Ting-Lei Gu, Roberto D Polakiewicz, Johannes L Roesel, Titus J Boggon, Fadlo R Khuri, D Gary Gilliland, Lewis C Cantley, Jonathan Kaufman, Jing Chen
发表日期
2009/11/17
期刊
Science signaling
卷号
2
期号
97
页码范围
ra73-ra73
出版商
American Association for the Advancement of Science
简介
The Warburg effect describes a pro-oncogenic metabolism switch such that cancer cells take up more glucose than normal tissue and favor incomplete oxidation of glucose even in the presence of oxygen. To better understand how tyrosine kinase signaling, which is commonly increased in tumors, regulates the Warburg effect, we performed phosphoproteomic studies. We found that oncogenic forms of fibroblast growth factor receptor type 1 inhibit the pyruvate kinase M2 (PKM2) isoform by direct phosphorylation of PKM2 tyrosine residue 105 (Y105). This inhibits the formation of active, tetrameric PKM2 by disrupting binding of the PKM2 cofactor fructose-1,6-bisphosphate. Furthermore, we found that phosphorylation of PKM2 Y105 is common in human cancers. The presence of a PKM2 mutant in which phenylalanine is substituted for Y105 (Y105F) in cancer cells leads to decreased cell proliferation under hypoxic …
引用总数
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T Hitosugi, S Kang, MG Vander Heiden, TW Chung… - Science signaling, 2009