ArticleMolecular cell2014
SAICAR induces protein kinase activity of PKM2 that is necessary for sustained proliferative signaling of cancer cells.
Article in Molecular cell, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 108 papers.
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Who cites it
108 citing papers in PubMed, 176 citations in OpenAlex.
- Targeting Pyruvate Kinase M2: Signal Transduction Pathways and Exploration of Cancer Therapeutic Strategies.The AAPS journal · 2026Review
- PKM2 Deficiency Results in Reduced Proliferation of Nasopharyngeal Carcinoma Cells by Deactivation of Nrf2-HO-1-GSH Signaling.Applied biochemistry and biotechnology · 2026Article
- Structural and molecular basis for allosteric regulation and catalytic coupling of human phosphoribosylformylglycinamidine synthase.Nature communications · 2026Article
- The moonlighting functions of glycolytic enzymes in tumorigenesis.Cellular oncology (Dordrecht, Netherlands) · 2026Review
- Enzyme Assemblies in Nucleotide Metabolism: Structure, Regulation, and Disease Implications.Advances in experimental medicine and biology · 2026Review
- Metabolic enzyme-associated protein-protein interactions (mPPIs) in cancer: potential vulnerability for cancer treatment?Acta pharmacologica Sinica · 2025Review
- Article
- The CLIC1-PKM2 axis orchestrates glycolytic metabolism to accelerate gastric cancer progression.Journal of translational medicine · 2025Article
- C1QBP forms a positive feedback loop with the PAICS/FAK/C-MYC axis to promote cancer cell proliferation.Oncogene · 2025Article
- Development of Cell-Permeable Adenylosuccinate Lyase Inhibitor.Methods and protocols · 2025Article
- Emerging role of complement system in the induction of neuroinflammation in adenylosuccinate lyase deficiency disorder.Brain, behavior, & immunity - health · 2025Review
- Nuclear PKM2: a signal receiver, a gene programmer, and a metabolic modulator.Journal of biomedical science · 2025Review
- Elucidating prognostic significance of purine metabolism in colorectal cancer through integrating data from transcriptomic, immunohistochemical, and single-cell RNA sequencing analysis.Molecular oncology · 2025Article
- Moonlighting functions of glucose metabolic enzymes and metabolites in cancer.Nature reviews. Cancer · 2025Review
- The role of fructose-1,6-bisphosphatase 1 on regulating the cancer progression and drug resistance.Discover oncology · 2025Review
- Review
- The emerging role of glycolysis and immune evasion in ovarian cancer.Cancer cell international · 2025Review
- Exploring glycolytic enzymes in disease: potential biomarkers and therapeutic targets in neurodegeneration, cancer and parasitic infections.Open biology · 2025Review
- Pyruvate Kinase M2-Responsive Release of Paclitaxel and Indoleamine 2,3-Dioxygenase Inhibitor for Immuno-Chemotherapy of Nonsmall Cell Lung Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- PKM2-mediated collagen XVII expression is critical for wound repair.JCI insight · 2025Article
48 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Abnormal metabolism and sustained proliferation are hallmarks of cancer. Pyruvate kinase M2 (PKM2) is a metabolic enzyme that plays important roles in both processes. Recently, PKM2 was shown to have protein kinase activity phosphorylating histone H3 and promoting cancer cell proliferation. However, the mechanism and extent of this protein kinase in cancer cells remain unclear. Here, we report that binding of succinyl-5-aminoimidazole-4-carboxamide-1-ribose-5'-phosphate (SAICAR), a metabolite abundant in proliferating cells, induces PKM2's protein kinase activity in vitro and in cells. Protein microarray experiments revealed that more than 100 human proteins, mostly protein kinases, are phosphorylated by PKM2-SAICAR. In particular, PKM2-SAICAR phosphorylates and activates Erk1/2, which in turn sensitizes PKM2 for SAICAR binding through phosphorylation. Additionally, PKM2-SAICAR was necessary to induce sustained Erk1/2 activation and mitogen-induced cell proliferation. Thus, the ligand-induced protein kinase activity from PKM2 is a mechanism that directly couples cell proliferation with intracellular metabolic status.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.