Article

PIM2 phosphorylates PKM2 and promotes Glycolysis in Cancer Cells.

Shanghai Jiao Tong University, China
Journal of Biological Chemistry (Impact Factor: 4.6). 10/2013; DOI: 10.1074/jbc.M113.508226
Source: PubMed

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 serine/threonine protein 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 Thr454 residue, resulting in an increase of PKM2 protein levels. Compared to 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 enhanced mitochondria respiration and chemotherapeutic sensitivity 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.

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