ArticleThe Journal of biological chemistry2015
Constitutive phosphorylation of cardiac myosin regulatory light chain in vivo.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 63 citations in OpenAlex.
- Modulating the myosin super-relaxed state as a therapeutic strategy for myosin light chain-linked cardiomyopathies.Biophysical reviews · 2026Review
- Biomolecular condensation of cMLCK enables myosin motor phosphorylation in the heart.bioRxiv : the preprint server for biology · 2026Article
- Spatial control of myosin regulatory light chain phosphorylation modulates cardiac thick filament mechanosensing.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- PPP1R12B inhibits cell proliferation by inducing G0/G1 phase arrest via PAK2/β-catenin axis in hepatocellular carcinoma.Frontiers in cell and developmental biology · 2025Article
- Mechanistic basis for rescuing hypertrophic cardiomyopathy with myosin regulatory light chain phosphorylation.Cytoskeleton (Hoboken, N.J.) · 2024Article
- Structure of mavacamten-free human cardiac thick filaments within the sarcomere by cryoelectron tomography.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Phosphorylation Mimetic of Myosin Regulatory Light Chain Mitigates Cardiomyopathy-Induced Myofilament Impairment in Mouse Models of RCM and DCM.Life (Basel, Switzerland) · 2023Article
- Pepducin ICL1-9-Mediated β2-Adrenergic Receptor-Dependent Cardiomyocyte Contractility Occurs in a GCardiovascular drugs and therapy · 2023Article
- NIMA-related kinase 9 regulates the phosphorylation of the essential myosin light chain in the heart.Nature communications · 2022Article
- Molecular basis of force-pCa relation inProceedings of the National Academy of Sciences of the United States of America · 2022Article
- Structural basis of the super- and hyper-relaxed states of myosin II.The Journal of general physiology · 2022Review
- Functional comparison of phosphomimetic S15D and T160D mutants of myosin regulatory light chain exchanged in cardiac muscle preparations of HCM and WT mice.Frontiers in cardiovascular medicine · 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
- Functional and Molecular Characterisation of Heart Failure Progression in Mice and the Role of Myosin Regulatory Light Chains in the Recovery of Cardiac Muscle Function.International journal of molecular sciences · 2021Article
- Cardiomyopathic mutations in essential light chain reveal mechanisms regulating the super relaxed state of myosin.The Journal of general physiology · 2021Article
- Mechanosignaling pathways alter muscle structure and function by post-translational modification of existing sarcomeric proteins to optimize energy usage.Journal of muscle research and cell motility · 2021Article
- Regulatory Light Chains in Cardiac Development and Disease.International journal of molecular sciences · 2021Review
- Stress-dependent activation of myosin in the heart requires thin filament activation and thick filament mechanosensing.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Cardiac myosin super relaxation (SRX): a perspective on fundamental biology, human disease and therapeutics.Biology open · 2021Review
- Mavacamten decreases maximal force and CaAmerican journal of physiology. Heart and circulatory physiology · 2021Article
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
In beating hearts, phosphorylation of myosin regulatory light chain (RLC) at a single site to 0.45 mol of phosphate/mol by cardiac myosin light chain kinase (cMLCK) increases Ca(2+) sensitivity of myofilament contraction necessary for normal cardiac performance. Reduction of RLC phosphorylation in conditional cMLCK knock-out mice caused cardiac dilation and loss of cardiac performance by 1 week, as shown by increased left ventricular internal diameter at end-diastole and decreased fractional shortening. Decreased RLC phosphorylation by conventional or conditional cMLCK gene ablation did not affect troponin-I or myosin-binding protein-C phosphorylation in vivo. The extent of RLC phosphorylation was not changed by prolonged infusion of dobutamine or treatment with a β-adrenergic antagonist, suggesting that RLC is constitutively phosphorylated to maintain cardiac performance. Biochemical studies with myofilaments showed that RLC phosphorylation up to 90% was a random process. RLC is slowly dephosphorylated in both noncontracting hearts and isolated cardiac myocytes from adult mice. Electrically paced ventricular trabeculae restored RLC phosphorylation, which was increased to 0.91 mol of phosphate/mol of RLC with inhibition of myosin light chain phosphatase (MLCP). The two RLCs in each myosin appear to be readily available for phosphorylation by a soluble cMLCK, but MLCP activity limits the amount of constitutive RLC phosphorylation. MLCP with its regulatory subunit MYPT2 bound tightly to myofilaments was constitutively phosphorylated in beating hearts at a site that inhibits MLCP activity. Thus, the constitutive RLC phosphorylation is limited physiologically by low cMLCK activity in balance with low MLCP activity.
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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.