Catalyzes the final rate-limiting step of glycolysis by mediating the transfer of a phosphoryl group from phosphoenolpyruvate (PEP) to ADP, generating ATP ( ). The ratio between the highly active tetrameric form and nearly inactive dimeric form determines whether glucose carbons are channeled to biosynthetic processes or used for glycolytic ATP production ( ). The transition between the 2 forms contributes to the control of glycolysis and is important for tumor cell proliferation and survival ( ).
Isoform specifically expressed during embryogenesis that has low pyruvate kinase activity by itself and requires allosteric activation by D-fructose 1,6-bisphosphate (FBP) for pyruvate kinase activity (, ). In addition to its pyruvate kinase activity in the cytoplasm, also acts as a regulator of transcription in the nucleus by acting as a protein kinase (  , ). Translocates into the nucleus in response to various signals, such as EGF receptor activation, and homodimerizes, leading to its conversion into a protein threonine- and tyrosine-protein kinase (  ). Catalyzes phosphorylation of STAT3 at 'Tyr-705' and histone H3 at 'Thr-11' (H3T11ph), leading to activate transcription ( ). Its ability to activate transcription plays a role in cancer cells by promoting cell proliferation and promote tumorigenesis ( ). Promotes the expression of the immune checkpoint protein CD274 in BMAL1-deficient macrophages (By similarity). May also act as a translation regulator for a subset of mRNAs, independently of its pyruvate kinase activity: associates with subpools of endoplasmic reticulum-associated ribosomes, binds directly to the mRNAs translated at the endoplasmic reticulum and promotes translation of these endoplasmic reticulum-destined mRNAs (By similarity). Plays a role in caspase independent cell death of tumor cells .
Pyruvate kinase isoform expressed in adult tissues, which replaces isoform M2 after birth . In contrast to isoform M2, has high pyruvate kinase activity by itself and does not require allosteric activation by D-fructose 1,6-bisphosphate (FBP) for activity .
Subcellular locations: Cytoplasm, Nucleus
Translocates to the nucleus in response to various signals, such as EGF receptor activation or apoptotic stimuli ( ). Nuclear translocation is promoted by acetylation by EP300 . Deacetylation by SIRT6 promotes its nuclear export in a process dependent of XPO4, thereby suppressing its ability to activate transcription and promote tumorigenesis .
Subcellular locations: Cytoplasm
Specifically expressed in proliferating cells, such as embryonic stem cells, embryonic carcinoma cells, as well as cancer cells.
Expressed in adult tissues . Not expressed in tumor cells .