?Pyruvate kinase (PK) regulates the final rate-limiting step of glycolysis in the production of pyruvate and adenosine triphosphate (ATP). Alternate splicing of PKM pre-mRNA leads to PKM2 generation by the inclusion of exon 10 and the exclusion of exon 9, which is specific for PKM1. Besides its cytosolic roles in glycolysis, PKM2, which is upregulated by growth factor receptor activation 1, is phosphorylated at S37 by extracellular signal-regulated kinase (ERK) 2. This phosphorylation leads to the cis-trans isomerization of PKM2 by the peptidyl-prolineisomerase protein interacting with never in mitosis A 1 (PIN1), exposure of the nuclear localization signal (NLS) of PKM2, and subsequent binding of importin α 5 for nuclear translocation 2. In the nucleus, PKM2binds to phosphorylated Y333 of β-catenin, which is essential for β-catenin transactivation 3, and interacts with and phosphorylates histone H3 at T11, leading to H3-K9 acetylation and transcription of genes such as MYC and CCND14. c-Myc expression results in the upregulation of GLUT1, lactate dehydrogenase A (LDHA), and, in a positive feedback loop, PTB-dependent PKM2, which subsequently enhances the Warburg effect 2. Cyclin D1 expression, in turn, promotes G1-S phase transition 3, 4.