title: Proviral insertion in murine lymphomas 2 (PIM2) oncogene phosphorylates pyruvate kinase M2 (PKM2) and promotes glycolysis in cancer cells.
abstract: Pyruvate kinase M2 (PKM2) is a key player in the Warburg effect of cancer cells. However, the mechanisms of regulating PKM2 are not fully elucidated. Here, we identified the protein-serine/threonine kinase PIM2, a known oncogene, as a novel binding partner of PKM2. The interaction between PIM2 and PKM2 was confirmed by multiple biochemical approaches in vitro and in cultured cells. Importantly, we found that PIM2 could directly phosphorylate PKM2 on the Thr-454 residue, resulting in an increase of PKM2 protein levels. Compared with wild type, PKM2 with the phosphorylation-defective mutation displayed a reduced effect on glycolysis, co-activating HIF-1α and β-catenin, and cell proliferation, while enhancing mitochondrial respiration of cancer cells. These findings demonstrate that PIM2-dependent phosphorylation of PKM2 is critical for regulating the Warburg effect in cancer, highlighting PIM2 as a potential therapeutic target.
authors.affiliation: From the School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200030, China.
authors.forename: Zhenhai
authors.initials: Z
authors.lastname: Yu
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Zhao
authors.forename: Liangqian
authors.initials: L
authors.lastname: Huang
authors.forename: Teng
authors.initials: T
authors.lastname: Zhang
authors.forename: Fajun
authors.initials: F
authors.lastname: Yang
authors.forename: Lei
authors.initials: L
authors.lastname: Xie
authors.forename: Shaoli
authors.initials: S
authors.lastname: Song
authors.forename: Ping
authors.initials: P
authors.lastname: Miao
authors.forename: Li
authors.initials: L
authors.lastname: Zhao
authors.forename: Xiaoguang
authors.initials: X
authors.lastname: Sun
authors.forename: Jianjun
authors.initials: J
authors.lastname: Liu
authors.forename: Gang
authors.initials: G
authors.lastname: Huang
mesh_terms: D045744:Cell Line, Tumor; D006019:Glycolysis; D057809:HEK293 Cells; D056945:Hep G2 Cells; D006801:Humans; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism*; D009857:Oncogenes; D010766:Phosphorylation; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism*; D011770:Pyruvate Kinase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D013912:Threonine / Q000737:chemistry; D020798:Two-Hybrid System Techniques; D016662:Virus Integration / Q000235:genetics*
chemical_list: C490587:PIM2 protein, human; D011518:Proto-Oncogene Proteins; D011993:Recombinant Fusion Proteins; D013912:Threonine; D011770:Pyruvate Kinase; D017346:Protein Serine-Threonine Kinases
keywords: Cancer; Cell Proliferation; Glycolysis; Phosphorylation; Pyruvate Kinase