ArticleNature communications2018
Protein phosphatase 5 regulates titin phosphorylation and function at a sarcomere-associated mechanosensor complex in cardiomyocytes.
Article in Nature communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
What it found
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Who cites it
30 citing papers in PubMed, 51 citations in OpenAlex.
- Nx3 Is a Z-Disk Structural and Signaling Hub That Is Reduced in Heart Failure.Circulation research · 2026Article
- Mechanisms of systolic heart failure in PP2CxPP5 double transgenic mice.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Selective titin cleavage disrupts cardiac mechanical homeostasis to drive heart failure and fibrosis.Nature cardiovascular research · 2026Article
- Mending the Achilles heels of titin in cardiac and musculoskeletal disease.Biophysical reviews · 2026Review
- Interaction of cardiac leiomodin with the native cardiac thin filament.PLoS biology · 2025Article
- SUMOylation of protein phosphatase 5 regulates phosphatase activity and substrate release.EMBO reports · 2024Article
- Titin: roles in cardiac function and diseases.Frontiers in physiology · 2024Review
- Summary statistics-based association test for identifying the pleiotropic effects with set of genetic variants.Bioinformatics (Oxford, England) · 2023Article
- Hypoxia-induced tracheal elasticity in vector beetle facilitates the loading of pinewood nematode.eLife · 2023Article
- Regulation of cardiac function by cAMP nanodomains.Bioscience reports · 2023Review
- Cryo-Electron Microscopy Reveals Cardiac Myosin Binding Protein-C M-Domain Interactions with the Thin Filament.Journal of molecular biology · 2022Article
- Increased protein phosphatase 5 expression in inflammation-induced left ventricular dysfunction in rats.BMC cardiovascular disorders · 2022Article
- Titin (TTN): from molecule to modifications, mechanics, and medical significance.Cardiovascular research · 2022Review
- The titin N2B and N2A regions: biomechanical and metabolic signaling hubs in cross-striated muscles.Biophysical reviews · 2021Review
- The ryanodine receptor stabilizer S107 ameliorates contractility of adult Rbm20 knockout rat cardiomyocytes.Physiological reports · 2021Article
- Mechanisms of Systolic Cardiac Dysfunction in PP2A, PP5 and PP2AxPP5 Double Transgenic Mice.International journal of molecular sciences · 2021Article
- Maintaining proteostasis under mechanical stress.EMBO reports · 2021Review
- Mechanisms ofJournal of cardiovascular development and disease · 2021Review
- Linagliptin prevents left ventricular stiffening by reducing titin cleavage and hypophosphorylation.Journal of cellular and molecular medicine · 2021Article
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Corrections and comments
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Authors and funding
11 authors at 7 institutions in 3 countries.
Funding
Abstract
Serine/threonine protein phosphatase 5 (PP5) is ubiquitously expressed in eukaryotic cells; however, its function in cardiomyocytes is unknown. Under basal conditions, PP5 is autoinhibited, but enzymatic activity rises upon binding of specific factors, such as the chaperone Hsp90. Here we show that PP5 binds and dephosphorylates the elastic N2B-unique sequence (N2Bus) of titin in cardiomyocytes. Using various binding and phosphorylation tests, cell-culture manipulation, and transgenic mouse hearts, we demonstrate that PP5 associates with N2Bus in vitro and in sarcomeres and is antagonistic to several protein kinases, which phosphorylate N2Bus and lower titin-based passive tension. PP5 is pathologically elevated and likely contributes to hypo-phosphorylation of N2Bus in failing human hearts. Furthermore, Hsp90-activated PP5 interacts with components of a sarcomeric, N2Bus-associated, mechanosensor complex, and blocks mitogen-activated protein-kinase signaling in this complex. Our work establishes PP5 as a compartmentalized, well-controlled phosphatase in cardiomyocytes, which regulates titin properties and kinase signaling at the myofilaments.
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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.