ArticleThe Journal of biological chemistry2016
Leucine Carboxyl Methyltransferase 1 (LCMT-1) Methylates Protein Phosphatase 4 (PP4) and Protein Phosphatase 6 (PP6) and Differentially Regulates the Stable Formation of Different PP4 Holoenzymes.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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27 citing papers in PubMed, 57 citations in OpenAlex.
- Activator mimicry by PP6 regulatory subunits directs Aurora A dephosphorylation in mitosis.The EMBO journal · 2026Article
- A functional map of phosphoprotein phosphatase regulation identifies an evolutionarily conserved reductase for the catalytic metal ions.Nature communications · 2026Article
- Pervasive phenotypic effects of FBXO42 are promoted by regulation of PP4 phosphatase.The EMBO journal · 2026Article
- PP2A methylesterase, PME-1, and PP2A methyltransferase, LCMT-1, control sensitivity to impairments caused by injury-related oligomeric tau.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- DynamicJournal of the American Chemical Society · 2025Article
- Protein serine/threonine phosphatases in tumor microenvironment: a vital player and a promising therapeutic target.Theranostics · 2025Review
- Direct mapping of ligandable tyrosines and lysines in cells with chiral sulfonyl fluoride probes.Nature chemistry · 2023Article
- Loss of LCMT1 and biased protein phosphatase 2A heterotrimerization drive prostate cancer progression and therapy resistance.Nature communications · 2023Article
- Identification of protein phosphatase 4 catalytic subunit as a Wnt promoting factor in pan-cancer and Xenopus early embryogenesis.Scientific reports · 2023Article
- PP2Acα-B'/PR61 Holoenzyme of Toxoplasma gondii Is Required for the Amylopectin Metabolism and Proliferation of Tachyzoites.Microbiology spectrum · 2023Article
- Eukaryotic-like Phosphoprotein Phosphatase (PPP) enzyme evolution: interactions with environmental toxins and regulatory proteins.Bioscience reports · 2023Article
- LCMT1 indicates poor prognosis and is essential for cell proliferation in hepatocellular carcinoma.Translational oncology · 2023Article
- Regulation of PP2A, PP4, and PP6 holoenzyme assembly by carboxyl-terminal methylation.Scientific reports · 2021Article
- Leucine Carboxyl Methyltransferase 1 Overexpression Protects Against Cognitive and Electrophysiological Impairments in Tg2576 APP Transgenic Mice.Journal of Alzheimer's disease : JAD · 2021Article
- Novel perspectives of target-binding by the evolutionarily conserved PP4 phosphatase.Open biology · 2020Article
- Effects of carboxyl-terminal methylation on holoenzyme function of the PP2A subfamily.Biochemical Society transactions · 2020Review
- Reduced Expression of the PP2A Methylesterase, PME-1, or the PP2A Methyltransferase, LCMT-1, Alters Sensitivity to Beta-Amyloid-Induced Cognitive and Electrophysiological Impairments in Mice.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2020Article
- Article
- Functional roles of protein phosphatase 4 in multiple aspects of cellular physiology: a friend and a foe.BMB reports · 2020Review
- Challenges and Reinterpretation of Antibody-Based Research on Phosphorylation of TyrCell reports · 2020Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The protein phosphatase 2A (PP2A) subfamily of phosphatases, PP2A, PP4, and PP6, are multifunctional serine/threonine protein phosphatases involved in many cellular processes. Carboxyl methylation of the PP2A catalytic subunit (PP2Ac) C-terminal leucine is regulated by the opposing activities of leucine carboxyl methyltransferase 1 (LCMT-1) and protein phosphatase methylesterase 1 (PME-1) and regulates PP2A holoenzyme formation. The site of methylation on PP2Ac is conserved in the catalytic subunits of PP4 and PP6, and PP4 is also methylated on that site, but the identities of the methyltransferase enzyme for PP4 are not known. Whether PP6 is methylated is also not known. Here we use antibodies specific for the unmethylated phosphatases to show that PP6 is carboxyl-methylated and that LCMT-1 is the major methyltransferase for PP2A, PP4, and PP6 in mouse embryonic fibroblasts (MEFs). Analysis of PP2A and PP4 complexes by blue native polyacrylamide gel electrophoresis (BN-PAGE) indicates that PP4 holoenzyme complexes, like those of PP2A, are differentially regulated by LCMT-1, with the PP4 regulatory subunit 1 (PP4R1)-containing PP4 complex being the most dramatically affected by the LCMT-1 loss. MEFs derived from LCMT-1 knock-out mouse embryos have reduced levels of PP2A B regulatory subunit and PP4R1 relative to control MEFs, indicating that LCMT-1 is important for maintaining normal levels of these subunits. Finally, LCMT-1 homozygous knock-out MEFs exhibited hyperphosphorylation of HDAC3, a reported target of the methylation-dependent PP4R1-PP4c complex. Collectively, our data suggest that LCMT-1 coordinately regulates the carboxyl methylation of PP2A-related phosphatases and, consequently, their holoenzyme assembly and function.
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