ArticleCell reports2019
Distinct Hepatic PKA and CDK Signaling Pathways Control Activity-Independent Pyruvate Kinase Phosphorylation and Hepatic Glucose Production.
Article in Cell reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 23 citations in OpenAlex.
- Fenitrothion induces sex-specific glucose metabolism dysregulation in rats by targeting PK/glycolysis in males and IDH3/TCA cycle in females.Archives of toxicology · 2026Article
- Symmetry-guided fusion converts weak liver pyruvate kinase inhibitors into potent allosteric activators.RSC medicinal chemistry · 2026Article
- Cysteine Metabolism in the Control of Oxidative Stress in Cancer, Focusing on Carbon and Sulfur Metabolism.Advances in experimental medicine and biology · 2026Review
- Potent Fluorescent Probe for Target-Engagement Studies of Allosteric Pyruvate Kinase Modulators.Angewandte Chemie (International ed. in English) · 2025Article
- Nuclear PKM2 binds pre-mRNA at folded G-quadruplexes and reveals their gene regulatory role.Molecular cell · 2024Article
- Importance of Michaelis Constants for Cancer Cell Redox Balance and Lactate Secretion-Revisiting the Warburg Effect.Cancers · 2024Review
- Genetic Encoding of Phosphorylated Amino Acids into Proteins.Chemical reviews · 2024Review
- PYK-SubstitutionOME: an integrated database containing allosteric coupling, ligand affinity and mutational, structural, pathological, bioinformatic and computational information about pyruvate kinase isozymes.Database : the journal of biological databases and curation · 2023Article
- Article
- Targeting Pyruvate Kinase M2 Phosphorylation Reverses Aggressive Cancer Phenotypes.Cancer research · 2021Article
- Multi-Tissue Acceleration of the Mitochondrial Phosphoenolpyruvate Cycle Improves Whole-Body Metabolic Health.Cell metabolism · 2020Article
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Authors and funding
19 authors at 3 institutions in 1 country.
Funding
Abstract
Pyruvate kinase is an important enzyme in glycolysis and a key metabolic control point. We recently observed a pyruvate kinase liver isoform (PKL) phosphorylation site at S113 that correlates with insulin resistance in rats on a 3 day high-fat diet (HFD) and suggests additional control points for PKL activity. However, in contrast to the classical model of PKL regulation, neither authentically phosphorylated PKL at S12 nor S113 alone is sufficient to alter enzyme kinetics or structure. Instead, we show that cyclin-dependent kinases (CDKs) are activated by the HFD and responsible for PKL phosphorylation at position S113 in addition to other targets. These CDKs control PKL nuclear retention, alter cytosolic PKL activity, and ultimately influence glucose production. These results change our view of PKL regulation and highlight a previously unrecognized pathway of hepatic CDK activity and metabolic control points that may be important in insulin resistance and type 2 diabetes.
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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.