ArticleJournal of molecular and cellular cardiology2015
Cardiac-specific deletion of protein phosphatase 1β promotes increased myofilament protein phosphorylation and contractile alterations.
Article in Journal of molecular and cellular cardiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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31 citing papers in PubMed, 51 citations in OpenAlex.
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- HuR inhibition reduces post-ischemic cardiac remodeling by dampening myocyte-dependent inflammatory gene expression and the innate immune response.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Cardiac myosin binding protein-C phosphorylation as a function of multiple protein kinase and phosphatase activities.Nature communications · 2024Article
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- Pharmacological analysis of Empagliflozin: Acting through the CaMKII pathway in type 2 diabetes and acute cardiovascular events.PloS one · 2022Article
- Regulation of myosin light-chain phosphorylation and its roles in cardiovascular physiology and pathophysiology.Hypertension research : official journal of the Japanese Society of Hypertension · 2022Review
- Protein phosphatase-1 inhibitor-2 promotes PP1Frontiers in synaptic neuroscience · 2022Article
- Role of Cardiac AMP-Activated Protein Kinase in a Non-pathological Setting: Evidence From Cardiomyocyte-Specific, Inducible AMP-Activated Protein Kinase α1α2-Knockout Mice.Frontiers in cell and developmental biology · 2021Article
- Heart Failure in Humans Reduces Contractile Force in Myocardium From Both Ventricles.JACC. Basic to translational science · 2020Article
- Differential expression of novel MicroRNAs from developing fetal heart of Gallus gallus domesticus implies a role in cardiac development.Molecular and cellular biochemistry · 2019Article
- Cardiomyocyte-Specific STIM1 (Stromal Interaction Molecule 1) Depletion in the Adult Heart Promotes the Development of Arrhythmogenic Discordant Alternans.Circulation. Arrhythmia and electrophysiology · 2019Article
- Cytoplasmic nucleic acid-based XNAs directly enhance live cardiac cell function by a CaJournal of molecular and cellular cardiology · 2019Article
- Differential localizations of protein phosphatase 1 isoforms determine their physiological function in the heart.Acta biochimica et biophysica Sinica · 2019Article
- The protein phosphatase isoform PP1γ1 substitutes for PP1γ2 to support spermatogenesis but not normal sperm function and fertility†.Biology of reproduction · 2019Article
- Phosphatases in Mitosis: Roles and Regulation.Biomolecules · 2019Review
- Functions and therapeutic potential of protein phosphatase 1: Insights from mouse genetics.Biochimica et biophysica acta. Molecular cell research · 2019Review
- The dominant protein phosphatase PP1c isoform in smooth muscle cells, PP1cβ, is essential for smooth muscle contraction.The Journal of biological chemistry · 2018Article
- Fibroblast-specific TGF-β-Smad2/3 signaling underlies cardiac fibrosis.The Journal of clinical investigation · 2017Article
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8 authors at 4 institutions in 1 country.
Funding
Abstract
There are 3 protein phosphatase 1 (PP1) catalytic isoforms (α, β and γ) encoded within the mammalian genome. These 3 gene products share ~90% amino acid homology within their catalytic domains but each has unique N- and C-termini that likely underlie distinctive subcellular localization or functionality. In this study, we assessed the effect associated with the loss of each PP1 isoform in the heart using a conditional Cre-loxP targeting approach in mice. Ppp1ca-loxP, Ppp1cb-loxP and Ppp1cc-loxP alleles were crossed with either an Nkx2.5-Cre knock-in containing allele for early embryonic deletion or a tamoxifen inducible α-myosin heavy chain (αMHC)-MerCreMer transgene for adult and cardiac-specific deletion. We determined that while deletion of Ppp1ca (PP1α) or Ppp1cc (PP1γ) had little effect on the whole heart, deletion of Ppp1cb (PP1β) resulted in concentric remodeling of the heart, interstitial fibrosis and contractile dysregulation, using either the embryonic or adult-specific Cre-expressing alleles. However, myocytes isolated from Ppp1cb deleted hearts surprisingly showed enhanced contractility. Mechanistically we found that deletion of any of the 3 PP1 gene-encoding isoforms had no effect on phosphorylation of phospholamban, nor were Ca(2+) handling dynamics altered in adult myocytes from Ppp1cb deleted hearts. However, the loss of Ppp1cb from the heart, but not Ppp1ca or Ppp1cc, resulted in elevated phosphorylation of myofilament proteins such as myosin light chain 2 and cardiac myosin binding protein C, consistent with an enriched localization profile of this isoform to the sarcomeres. These results suggest a unique functional role for the PP1β isoform in affecting cardiac contractile function.
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