3BJF

Pyruvate kinase M2 is a phosphotyrosine binding protein

3BJF の概要

• エントリーDOI: 10.2210/pdb3bjf/pdb
• 分子名称: Pyruvate kinase isozymes M1/M2, 1,6-di-O-phosphono-beta-D-fructofuranose, OXALATE ION, ... (6 entities in total)
• 機能のキーワード: pyruvate kinase, acetylation, allosteric enzyme, alternative splicing, glycolysis, magnesium, metal-binding, phosphoprotein, polymorphism, transferase
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 228499.15

構造登録者

Wu, N. (登録日: 2007-12-03, 公開日: 2008-03-04, 最終更新日: 2024-02-21)

主引用文献

Christofk, H.R.,Vander Heiden, M.G.,Wu, N.,Asara, J.M.,Cantley, L.C.
Pyruvate kinase M2 is a phosphotyrosine-binding protein.
Nature, 452:181-186, 2008

PubMed Abstract: Growth factors stimulate cells to take up excess nutrients and to use them for anabolic processes. The biochemical mechanism by which this is accomplished is not fully understood but it is initiated by phosphorylation of signalling proteins on tyrosine residues. Using a novel proteomic screen for phosphotyrosine-binding proteins, we have made the observation that an enzyme involved in glycolysis, the human M2 (fetal) isoform of pyruvate kinase (PKM2), binds directly and selectively to tyrosine-phosphorylated peptides. We show that binding of phosphotyrosine peptides to PKM2 results in release of the allosteric activator fructose-1,6-bisphosphate, leading to inhibition of PKM2 enzymatic activity. We also provide evidence that this regulation of PKM2 by phosphotyrosine signalling diverts glucose metabolites from energy production to anabolic processes when cells are stimulated by certain growth factors. Collectively, our results indicate that expression of this phosphotyrosine-binding form of pyruvate kinase is critical for rapid growth in cancer cells.

PubMed: 18337815
DOI: 10.1038/nature06667

実験手法

X-RAY DIFFRACTION (2.03 Å)