ArticleCirculation2012
Myosin light chain phosphorylation is critical for adaptation to cardiac stress.
Article in Circulation, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.
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Who cites it
69 citing papers in PubMed, 103 citations in OpenAlex.
- Capturing Cardiomyocyte Cell-to-Cell Heterogeneity via Shotgun Single Cell Top-Down Proteomics.bioRxiv : the preprint server for biology · 2026Article
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- The Network of Exosomes miRNA and p-MLC2 Regulatory Pathway Induced Pathological Cardiac Hypertrophy in Vasn Deficient Mice.Journal of cellular and molecular medicine · 2025Article
- The circRNA-mediated ceRNA molecular regulatory network in fatigue-type type 2 diabete.Journal of translational medicine · 2025Article
- Elevated uric acid induces erectile dysfunction in rats by interacting with MLCK and inhibiting its ubiquitin-mediated degradation.Communications biology · 2025Article
- Increased resting heart rate indicates high-workload hearts with augmented aortic hydraulic power in hypertensive pigs.PloS one · 2025Article
- ALPK2 prevents cardiac diastolic dysfunction in heart failure with preserved ejection fraction.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
- The structural and functional effects of myosin regulatory light chain phosphorylation are amplified by increases in sarcomere length and [CaThe Journal of physiology · 2024Article
- Carvedilol Activates a Myofilament Signaling Circuitry to Restore Cardiac Contractility in Heart Failure.JACC. Basic to translational science · 2024Article
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- Multi-Omics Profiling of Hypertrophic Cardiomyopathy Reveals Altered Mechanisms in Mitochondrial Dynamics and Excitation-Contraction Coupling.International journal of molecular sciences · 2023Article
- PD-1 Alleviates Cisplatin-Induced Muscle Atrophy by Regulating Inflammation and Oxidative Stress.Antioxidants (Basel, Switzerland) · 2022Article
- Constitutive protein kinase G activation exacerbates stress-induced cardiomyopathy.British journal of pharmacology · 2022Article
- Calpains as Potential Therapeutic Targets for Myocardial Hypertrophy.International journal of molecular sciences · 2022Review
- Loss of cardiac myosin light chain kinase contributes to contractile dysfunction in right ventricular pressure overload.Physiological reports · 2022Article
- Understanding the molecular basis of cardiomyopathy.American journal of physiology. Heart and circulatory physiology · 2022Review
- 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
- Hypertrophic cardiomyopathy associated E22K mutation in myosin regulatory light chain decreases calcium-activated tension and stiffness and reduces myofilament CaThe FEBS journal · 2021Article
- Proteomics study on the effect of silybin on cardiomyopathy in obese mice.Scientific reports · 2021Article
9 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
15 authors at 6 institutions in 2 countries.
Funding
Abstract
backgroundCardiac hypertrophy is a common response to circulatory or neurohumoral stressors as a mechanism to augment contractility. When the heart is under sustained stress, the hypertrophic response can evolve into decompensated heart failure, although the mechanism(s) underlying this transition remain largely unknown. Because phosphorylation of cardiac myosin light chain 2 (MLC2v), bound to myosin at the head-rod junction, facilitates actin-myosin interactions and enhances contractility, we hypothesized that phosphorylation of MLC2v plays a role in the adaptation of the heart to stress. We previously identified an enzyme that predominantly phosphorylates MLC2v in cardiomyocytes, cardiac myosin light-chain kinase (cMLCK), yet the role(s) played by cMLCK in regulating cardiac function in health and disease remain to be determined. METHODS AND
resultsWe found that pressure overload induced by transaortic constriction in wild-type mice reduced phosphorylated MLC2v levels by ≈40% and cMLCK levels by ≈85%. To examine how a reduction in cMLCK and the corresponding reduction in phosphorylated MLC2v affect function, we generated Mylk3 gene-targeted mice and transgenic mice overexpressing cMLCK specifically in cardiomyocytes. Pressure overload led to severe heart failure in cMLCK knockout mice but not in mice with cMLCK overexpression in which cMLCK protein synthesis exceeded degradation. The reduction in cMLCK protein during pressure overload was attenuated by inhibition of ubiquitin-proteasome protein degradation systems.
conclusionsOur results suggest the novel idea that accelerated cMLCK protein turnover by the ubiquitin-proteasome system underlies the transition from compensated hypertrophy to decompensated heart failure as a result of reduced phosphorylation of MLC2v.
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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.