ArticleThe Journal of biological chemistry2011
Phosphoinositide 3-kinase (PI3K(p110alpha)) directly regulates key components of the Z-disc and cardiac structure.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 36 citations in OpenAlex.
- MicroRNA expression, target genes, and signaling pathways in infants with a ventricular septal defect.Molecular and cellular biochemistry · 2018Trial
- CCDC141 is a Connectin/Titin and Nesprin-1 binding protein that adapts cardiomyocytes to mechanical stress.Communications biology · 2025Article
- Effect of High-Intensity Interval Training on Cardiac Apoptosis Markers in Methamphetamine-Dependent Rats.Current issues in molecular biology · 2022Article
- Filamin C in cardiomyopathy: from physiological roles to DNA variants.Heart failure reviews · 2022Review
- Review
- The intercalated disc: a mechanosensing signalling node in cardiomyopathy.Biophysical reviews · 2020Review
- Loss of melusin is a novel, neuronal NO synthase/FoxO3-independent master switch of unloading-induced muscle atrophy.Journal of cachexia, sarcopenia and muscle · 2020Article
- Phosphoproteomics identifies dual-site phosphorylation in an extended basophilic motif regulating FILIP1-mediated degradation of filamin-C.Communications biology · 2020Article
- For Better or Worse: The Potential for Dose Limiting the On-Target Toxicity of PI 3-Kinase Inhibitors.Biomolecules · 2019Review
- Zebrafish VCAP1X2 regulates cardiac contractility and proliferation of cardiomyocytes and epicardial cells.Scientific reports · 2018Article
- Progesterone signalling in broiler skeletal muscle is associated with divergent feed efficiency.BMC systems biology · 2017Article
- Identification of the molecular mechanisms underlying dilated cardiomyopathy via bioinformatic analysis of gene expression profiles.Experimental and therapeutic medicine · 2017Article
- Melusin Promotes a Protective Signal Transduction Cascade in Stressed Hearts.Frontiers in molecular biosciences · 2016Review
- Nexilin, a cardiomyopathy-associated F-actin binding protein, binds and regulates IRS1 signaling in skeletal muscle cells.PloS one · 2013Article
- Enhanced phosphoinositide 3-kinase(p110α) activity prevents diabetes-induced cardiomyopathy and superoxide generation in a mouse model of diabetes.Diabetologia · 2012Article
- Actin in striated muscle: recent insights into assembly and maintenance.Biophysical reviews · 2012Review
Corrections and comments
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Authors and funding
11 authors at 7 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Maintenance of cardiac structure and Z-disc signaling are key factors responsible for protecting the heart in a setting of stress, but how these processes are regulated is not well defined. We recently demonstrated that PI3K(p110α) protects the heart against myocardial infarction. The aim of this study was to determine whether PI3K(p110α) directly regulates components of the Z-disc and cardiac structure. To address this question, a unique three-dimensional virtual muscle model was applied to gene expression data from transgenic mice with increased or decreased PI3K(p110α) activity under basal conditions (sham) and in a setting of myocardial infarction to display the location of structural proteins. Key findings from this analysis were then validated experimentally. The three-dimensional virtual muscle model visually highlighted reciprocally regulated transcripts associated with PI3K activation that encoded key components of the Z-disc and costamere, including melusin. Studies were performed to assess whether PI3K and melusin interact in the heart. Here, we identify a novel melusin-PI3K interaction that generates lipid kinase activity. The direct impact of PI3K(p110α) on myocyte structure was assessed by treating neonatal rat ventricular myocytes with PI3K(p110α) inhibitors and examining the myofiber morphology of hearts from PI3K transgenic mice. Results demonstrate that PI3K is critical for myofiber maturation and Z-disc alignment. In summary, PI3K regulates the expression of genes essential for cardiac structure and Z-disc signaling, interacts with melusin, and is critical for Z-disc alignment.
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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.