ArticleThe Journal of clinical investigation2009
Protein phosphatase 2Cm is a critical regulator of branched-chain amino acid catabolism in mice and cultured cells.
Article in The Journal of clinical investigation, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 128 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
128 citing papers in PubMed, 1 synthesis or guideline pooled it, 218 citations in OpenAlex.
- Genetic Predisposition to an Impaired Metabolism of the Branched-Chain Amino Acids and Risk of Type 2 Diabetes: A Mendelian Randomisation Analysis.PLoS medicine · 2016Pooled it
- Loss of TAFAZZIN leads to perturbation of amino acid metabolism and reduction of collagen synthesis.bioRxiv : the preprint server for biology · 2026Article
- The Complex Relation of Branched-Chain Amino Acids and Inflammation in the Obesity and Diabetes Context.Obesity reviews : an official journal of the International Association for the Study of Obesity · 2026Review
- Branched-chain amino acid catabolism is potentially deficient in pancreatic cancer with high-neural invasion.Scientific reports · 2026Article
- Branched-chain amino acid metabolism and macrophage polarization: potential regulatory nodes and therapeutic targets in diabetes-associated metabolic inflammation.Frontiers in cellular and infection microbiology · 2026Review
- Aloe emodin attenuates AβOpen medicine (Warsaw, Poland) · 2026Article
- Branched-chain amino acids and sepsis: from pathological mechanisms to clinical interventions.Nutrition & metabolism · 2025Review
- Multimodal Therapeutic Strategies Targeting BCAA Metabolism in Diabetic Cardiomyopathy: A Path to Cardioprotection.Cardiovascular toxicology · 2025Review
- Mitochondrial Dynamics in Aging Heart.Biomedicines · 2025Review
- Short-term Physical Activity Reduces Metabolic-associated Steatohepatitis by Promoting the Degradation of Branched-chain Amino Acids in Skeletal Muscle.Journal of clinical and translational hepatology · 2025Article
- Phosphatase activity-based PPM1K: a key player in the regulation of mitochondrial function and its multifaceted impact in diseases.Molecular and cellular biochemistry · 2025Review
- Branched-chain amino acids promote hepatic Cyp7a1 expression and bile acid synthesis via suppressing FGF21-ERK pathway.Acta pharmacologica Sinica · 2025Article
- Branched-chain amino acid metabolism: Pathophysiological mechanism and therapeutic intervention in metabolic diseases.Obesity reviews : an official journal of the International Association for the Study of Obesity · 2025Review
- Pantothenate kinase 4 controls skeletal muscle substrate metabolism.Nature communications · 2025Article
- Multi-omics insights into the pathogenesis of diabetic cardiomyopathy: epigenetic and metabolic profiles.Epigenomics · 2025Article
- Effects of BCAA supplementation on plasma and mare's milk amino acid contents inFrontiers in veterinary science · 2025Article
- Primary Roles of Branched Chain Amino Acids (BCAAs) and Their Metabolism in Physiology and Metabolic Disorders.Molecules (Basel, Switzerland) · 2024Review
- Identification of putative allosteric inhibitors of BCKDK via virtual screening and biological evaluation.Journal of enzyme inhibition and medicinal chemistry · 2024Article
- Bicyclic Inhibitors of Branched-Chain α-Keto Acid Dehydrogenase Kinase (BDK) with In Vivo Activity.ACS medicinal chemistry letters · 2024Article
- BCKDH kinase promotes hepatic gluconeogenesis independent of BCKDHA.Cell death & disease · 2024Article
68 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
The branched-chain amino acids (BCAA) are essential amino acids required for protein homeostasis, energy balance, and nutrient signaling. In individuals with deficiencies in BCAA, these amino acids can be preserved through inhibition of the branched-chain-alpha-ketoacid dehydrogenase (BCKD) complex, the rate-limiting step in their metabolism. BCKD is inhibited by phosphorylation of its E1alpha subunit at Ser293, which is catalyzed by BCKD kinase. During BCAA excess, phosphorylated Ser293 (pSer293) becomes dephosphorylated through the concerted inhibition of BCKD kinase and the activity of an unknown intramitochondrial phosphatase. Using unbiased, proteomic approaches, we have found that a mitochondrial-targeted phosphatase, PP2Cm, specifically binds the BCKD complex and induces dephosphorylation of Ser293 in the presence of BCKD substrates. Loss of PP2Cm completely abolished substrate-induced E1alpha dephosphorylation both in vitro and in vivo. PP2Cm-deficient mice exhibited BCAA catabolic defects and a metabolic phenotype similar to the intermittent or intermediate types of human maple syrup urine disease (MSUD), a hereditary disorder caused by defects in BCKD activity. These results indicate that PP2Cm is the endogenous BCKD phosphatase required for nutrient-mediated regulation of BCKD activity and suggest that defects in PP2Cm may be responsible for a subset of human MSUD.
Indexed as
Identifiers
What OpenQuestion holds
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.