ArticleProtein & cell2015
Structural insight into mechanisms for dynamic regulation of PKM2.
Article in Protein & cell, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.
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Who cites it
69 citing papers in PubMed, 125 citations in OpenAlex.
- PKM2-Mediated Glycolytic Reprogramming in Thyroid Cancer: Mechanistic Insights and Therapeutic Potential.Molecules (Basel, Switzerland) · 2026Review
- Acarbose modulates microglial Pkm2 acetylation to reshape immunometabolism and preserve retinal neurons after ischemia-reperfusion.Journal of neuroinflammation · 2026Article
- Review
- PKM2 phosphorylation by c-SRC activates glycolysis and metastasis with the stimulation of tumor-associated macrophages.Cell communication and signaling : CCS · 2026Article
- PKM2 preconditioning protects endothelial cells from pyroptosis and BBB disruption via NRF2/TRX/TXNIP signaling in neonatal hypoxic-ischemic brain injury.Journal of neuroinflammation · 2026Article
- Pyruvate kinase M2 in Alzheimer's disease: from dysregulation to therapeutic inhibition.Brain communications · 2026Review
- PKM2 mediates the glycolytic response to matrix stiffness in lung fibroblasts.Frontiers in cell and developmental biology · 2026Article
- GSH as an A-A Type Allosteric Activator of PKM2: Modulating Cancer Cell Homeostasis and Ferroptosis Susceptibility.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Isoform-specific regulation of PKM by acetylation.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Hypoxia-induced MT2A-tetrameric PKM2 interaction maintains PKM2 activity in a copper-ion-dependent manner.Cell insight · 2025Article
- Glycolysis to lactylation: Unraveling the metabolic and epigenetic landscape in tissue fibrosis (Review).Molecular medicine reports · 2025Review
- Macrophage junctional adhesion molecule-like (JAML) protein promotes NLRP3 inflammasome activation in the development of atherosclerosis.Cell death and differentiation · 2025Article
- SETD5 facilitates stemness and represses ferroptosis via m6A-mediating PKM2 stabilization in non-small cell lung cancer.Oncogene · 2025Article
- PKM2, the "K+ sink" in the tumor interstitial fluid.Protein & cell · 2025Article
- PKM2-mediated metabolic reprogramming of microglia in neuroinflammation.Cell death discovery · 2025Review
- High-Resolution Molecular-Dynamics Simulations of the Pyruvate Kinase Muscle Isoform 1 and 2 (PKM1/2).Chemistry (Weinheim an der Bergstrasse, Germany) · 2025Article
- Review
- Palmitic Acid Accelerates Endothelial Cell Injury and Cardiovascular Dysfunction via Palmitoylation of PKM2.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Flavonoids in Brain Ischemia-Reperfusion and their Effect on Kinases as Signaling Pathway Activity.CNS & neurological disorders drug targets · 2025Article
- PKM2 orchestrates tumor progression via metabolic reprogramming and MDSCs-mediated immune suppression in the tumor microenvironment.Frontiers in immunology · 2025Review
9 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pyruvate kinase isoform M2 (PKM2) converts phosphoenolpyruvate (PEP) to pyruvate and plays an important role in cancer metabolism. Here, we show that post-translational modifications and a patient-derived mutation regulate pyruvate kinase activity of PKM2 through modulating the conformation of the PKM2 tetramer. We determined crystal structures of human PKM2 mutants and proposed a "seesaw" model to illustrate conformational changes between an inactive T-state and an active R-state tetramers of PKM2. Biochemical and structural analyses demonstrate that PKM2(Y105E) (phosphorylation mimic of Y105) decreases pyruvate kinase activity by inhibiting FBP (fructose 1,6-bisphosphate)-induced R-state formation, and PKM2(K305Q) (acetylation mimic of K305) abolishes the activity by hindering tetramer formation. K422R, a patient-derived mutation of PKM2, favors a stable, inactive T-state tetramer because of strong intermolecular interactions. Our study reveals the mechanism for dynamic regulation of PKM2 by post-translational modifications and a patient-derived mutation and provides a structural basis for further investigation of other modifications and mutations of PKM2 yet to be discovered.
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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.