PKM

GeneName

PKM

Summary

PKM, also known as PKM2, p58, or PK2, is a 58 kDa enzyme that plays a pivotal role in the regulation of glycolysis and the metabolic pathways associated with energy production. It is predominantly expressed in the cytoplasm and is involved in various cellular processes, including the cellular response to insulin and the regulation of transcription. PKM functions as a pyruvate kinase, catalysing the conversion of phosphoenolpyruvate to pyruvate, and is also known for its involvement in protein homodimerization and kinase activities, including histone H3T11 kinase activity. Additionally, it has been implicated in processes such as angiogenesis and programmed cell death, highlighting its multifaceted role in cellular metabolism and signalling.

Importance

PKM is relevant to: - Cancer metabolism, as its expression and activity can influence the Warburg effect and tumour growth. - Metabolic disorders, given its role in glycolysis and insulin response, which may affect glucose homeostasis. - Angiogenesis, through its involvement in the positive regulation of sprouting angiogenesis, impacting tumour vascularisation and progression. - Cellular differentiation and development, due to its regulatory effects on transcription and translation processes.

Top Products

For researchers investigating PKM, we recommend two excellent primary antibodies. The first is the well-cited polyclonal antibody, Anti-PKM antibody (ab137852), which has garnered 55 citations, reflecting its reliability in the field. This antibody is particularly effective for Western blotting (WB), immunohistochemistry (IHC), and immunocytochemistry (ICC). In addition, we offer the recombinant antibody, Anti-PKM antibody [EPR10138(B)] (ab150377). This product has been validated for use in WB, ICC, and flow cytometry (FC), making it a versatile option for various experimental needs. With 39 citations, it is also gaining recognition among researchers. The recombinant nature of this antibody ensures batch-to-batch consistency, which is invaluable for reproducible results in your studies.

Abcam Product Citation Summary

The data indicates that PKM is being extensively studied in the context of melanoma, particularly in relation to cell proliferation, metabolism, and the effects of specific microRNAs. Additionally, PKM is being investigated in human xenografts and pancreatic adenocarcinoma (PAAD) cells, focusing on glycolysis suppression. The use of PKM antibodies in various applications, including western blotting and flow cytometry, highlights its significance in cancer research and thymocyte development.

Abcam Product Citation Table

Developmental stage

Isoform M2

Specifically expressed during embryonic development.

Isoform M1

Specifically expressed in adult tissues.

Function

Catalyzes the final rate-limiting step of glycolysis by mediating the transfer of a phosphoryl group from phosphoenolpyruvate (PEP) to ADP, generating ATP (PubMed:15996096, PubMed:1854723, PubMed:20847263). 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 (PubMed:15996096, PubMed:1854723, PubMed:20847263). The transition between the 2 forms contributes to the control of glycolysis and is important for tumor cell proliferation and survival (PubMed:15996096, PubMed:1854723, PubMed:20847263).

Isoform M2

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 (PubMed:18337823, PubMed:20847263). 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 (PubMed:18191611, PubMed:21620138, PubMed:22056988, PubMed:22306293, PubMed:22901803, PubMed:24120661). 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 (PubMed:22056988, PubMed:22306293, PubMed:22901803, PubMed:24120661, PubMed:26787900). Catalyzes phosphorylation of STAT3 at 'Tyr-705' and histone H3 at 'Thr-11' (H3T11ph), leading to activate transcription (PubMed:22306293, PubMed:22901803, PubMed:24120661). Its ability to activate transcription plays a role in cancer cells by promoting cell proliferation and promote tumorigenesis (PubMed:18337823, PubMed:22901803, PubMed:26787900). 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 (PubMed:17308100).

Isoform M1

Pyruvate kinase isoform expressed in adult tissues, which replaces isoform M2 after birth (PubMed:18337823). 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 (PubMed:20847263).

Pathway

Carbohydrate degradation; glycolysis; pyruvate from D-glyceraldehyde 3-phosphate: step 5/5.

Post-translational modifications

ISGylated.

Under hypoxia, hydroxylated by EGLN3.

Acetylation at Lys-305 is stimulated by high glucose concentration, it decreases enzyme activity and promotes its lysosomal-dependent degradation via chaperone-mediated autophagy.

Isoform M2

Acetylated at Lys-433 by EP300, leading to impair phosphoenolpyruvate substrate-binding and promote its homodimerization and subsequent translocation to the nucleus (PubMed:24120661). Deacetylation at Lys-433 by SIRT6 promotes its nuclear export into the cytoplasm, leading to suppress its nuclear localization and oncogenic function (PubMed:26787900).

Isoform M2

S-nitrosylation at Cys-423 and Cys-424 inhibits homotetramerization and pyruvate kinase activity (PubMed:30487609). S-nitrosylation is indirectly inhibited by AKR1A1 which degrades S-nitroso-CoA, a cofactor required to S-nitrosylate proteins (PubMed:30487609).

FGFR1-dependent tyrosine phosphorylation is reduced by interaction with TRIM35.

Sequence Similarities

Belongs to the pyruvate kinase family.

Tissue Specificity

Isoform M2

Specifically expressed in proliferating cells, such as embryonic stem cells, embryonic carcinoma cells, as well as cancer cells.

Isoform M1

Expressed in adult tissues (PubMed:18337823). Not expressed in tumor cells (PubMed:18337823).

Cellular localization

• Isoform M2
• Cytoplasm
• Nucleus
• Translocates to the nucleus in response to various signals, such as EGF receptor activation or apoptotic stimuli (PubMed:17308100, PubMed:22056988, PubMed:24120661). Nuclear translocation is promoted by acetylation by EP300 (PubMed:24120661). Deacetylation by SIRT6 promotes its nuclear export in a process dependent of XPO4, thereby suppressing its ability to activate transcription and promote tumorigenesis (PubMed:26787900).
• Isoform M1
• Cytoplasm

Alternative names

OIP3, PK2, PK3, PKM2, PKM, Pyruvate kinase PKM, Cytosolic thyroid hormone-binding protein, Opa-interacting protein 3, Pyruvate kinase 2/3, Pyruvate kinase muscle isozyme, Threonine-protein kinase PKM2, Thyroid hormone-binding protein 1, Tumor M2-PK, Tyrosine-protein kinase PKM2, p58, CTHBP, OIP-3, THBP1

Database links

swissprot:P14618 entrezGene:5315 omim:179050

Other research areas

• Immunology & Infectious Disease