@article{88156,
  keywords = {Animals, Models, Molecular, Humans, phosphorylation, Molecular Sequence Data, Histidine, Cell Proliferation, Amino Acid Sequence, Mice, Cell Line, Tumor, Glycolysis, Neoplasms, Phosphotyrosine, Enzyme Stability, 2,3-Diphosphoglycerate, Glyceric Acids, Phosphoglycerate Mutase},
  author = {Taro Hitosugi and Lu Zhou and Jun Fan and Shannon Elf and Liang Zhang and Jianxin Xie and Yi Wang and Ting-Lei Gu and Masa Ale{\v c}kovi{\'c} and Gary LeRoy and Yibin Kang and Hee-Bum Kang and Jae-Ho Seo and Changliang Shan and Peng Jin and Weimin Gong and Sagar Lonial and Martha Arellano and Hanna Khoury and Georgia Chen and Dong Shin and Fadlo Khuri and Titus Boggon and Sumin Kang and Chuan He and Jing Chen},
  title = {Tyr26 phosphorylation of PGAM1 provides a metabolic advantage to tumours by stabilizing the active conformation.},
  abstract = { How oncogenic signalling coordinates glycolysis and anabolic biosynthesis in cancer cells remains unclear. We recently reported that the glycolytic enzyme phosphoglycerate mutase 1 (PGAM1) regulates anabolic biosynthesis by controlling intracellular levels of its substrate 3-phosphoglycerate and product 2-phosphoglycerate. Here we report a novel mechanism in which Y26 phosphorylation enhances PGAM1 activation through release of inhibitory E19 that blocks the active site, stabilising cofactor 2,3-bisphosphoglycerate binding and H11 phosphorylation. We also report the crystal structure of H11-phosphorylated PGAM1 and find that phospho-H11 activates PGAM1 at least in part by promoting substrate 3-phosphoglycerate binding. Moreover, Y26 phosphorylation of PGAM1 is common in human cancer cells and contributes to regulation of 3-phosphoglycerate and 2-phosphoglycerate levels, promoting cancer cell proliferation and tumour growth. As PGAM1 is a negative transcriptional target of TP53, and is therefore commonly upregulated in human cancers, these findings suggest that Y26 phosphorylation represents an additional acute mechanism underlying phosphoglycerate mutase 1 upregulation. },
  year = {2013},
  journal = {Nat Commun},
  volume = {4},
  pages = {1790},
  issn = {2041-1723},
  doi = {10.1038/ncomms2759},
  language = {eng},
}