ArticleProceedings of the National Academy of Sciences of the United States of America2016
Cardiac myosin light chain is phosphorylated by Ca2+/calmodulin-dependent and -independent kinase activities.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 53 citations in OpenAlex.
- Advances in Understanding Calcium Sensitization in Gastrointestinal Smooth Muscles: Pathways, Interstitial Cells, and Disease.Journal of neurogastroenterology and motility · 2026Review
- Biomolecular condensation of cMLCK enables myosin motor phosphorylation in the heart.bioRxiv : the preprint server for biology · 2026Article
- A study based on reverse network pharmacology of kidney stones identified that quercetin targets the myosin light chain kinase/myosin light chain 2 pathway in human renal HK-2 cells.Asian journal of urology · 2026Article
- MLC2: Physiological Functions and Potential Roles in Tumorigenesis.Cell biochemistry and biophysics · 2025Review
- CaCurrent biology : CB · 2025Article
- Structure of the Inhibited Smooth Muscle Myosin and Its Implications on the Regulation of Insect Striated Muscle Myosin.Life (Basel, Switzerland) · 2025Review
- Histone H2A.Z Deacetylation and Dedifferentiation in Infarcted/Tip60-depleted Cardiomyocytes.bioRxiv : the preprint server for biology · 2025Article
- Dual effect of N-terminal deletion of cardiac myosin essential light chain in mitigating cardiomyopathy.iScience · 2024Article
- Myofilament dysfunction in diastolic heart failure.Heart failure reviews · 2024Review
- Molecular Insights into the MLCK Activation by CaM.Journal of chemical information and modeling · 2023Article
- An extensive β1-adrenergic receptor gene signaling network regulates molecular remodeling in dilated cardiomyopathies.JCI insight · 2023Article
- Mechanisms of Sarcomere Protein Mutation-Induced Cardiomyopathies.Current cardiology reports · 2023Review
- Mathematical modeling and biochemical analysis support partially ordered calmodulin-myosin light chain kinase binding.iScience · 2023Article
- Cardiac Sarcomere Signaling in Health and Disease.International journal of molecular sciences · 2022Review
- NIMA-related kinase 9 regulates the phosphorylation of the essential myosin light chain in the heart.Nature communications · 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 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
- Impact of regulatory light chain mutation K104E on the ATPase and motor properties of cardiac myosin.The Journal of general physiology · 2021Article
- Striated Preferentially Expressed Protein Kinase (SPEG) in Muscle Development, Function, and Disease.International journal of molecular sciences · 2021Review
- Protective effects of curcumin against rat intestinal inflammation‑related motility disorders.Molecular medicine reports · 2021Article
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Authors and funding
7 authors at 5 institutions in 3 countries.
Funding
Abstract
The well-known, muscle-specific smooth muscle myosin light chain kinase (MLCK) (smMLCK) and skeletal muscle MLCK (skMLCK) are dedicated protein kinases regulated by an autoregulatory segment C terminus of the catalytic core that blocks myosin regulatory light chain (RLC) binding and phosphorylation in the absence of Ca(2+)/calmodulin (CaM). Although it is known that a more recently discovered cardiac MLCK (cMLCK) is necessary for normal RLC phosphorylation in vivo and physiological cardiac performance, information on cMLCK biochemical properties are limited. We find that a fourth uncharacterized MLCK, MLCK4, is also expressed in cardiac muscle with high catalytic domain sequence similarity with other MLCKs but lacking an autoinhibitory segment. Its crystal structure shows the catalytic domain in its active conformation with a short C-terminal "pseudoregulatory helix" that cannot inhibit catalysis as a result of missing linker regions. MLCK4 has only Ca(2+)/CaM-independent activity with comparable Vmax and Km values for different RLCs. In contrast, the Vmax value of cMLCK is orders of magnitude lower than those of the other three MLCK family members, whereas its Km (RLC and ATP) and KCaM values are similar. In contrast to smMLCK and skMLCK, which lack activity in the absence of Ca(2+)/CaM, cMLCK has constitutive activity that is stimulated by Ca(2+)/CaM. Potential contributions of autoregulatory segment to cMLCK activity were analyzed with chimeras of skMLCK and cMLCK. The constitutive, low activity of cMLCK appears to be intrinsic to its catalytic core structure rather than an autoinhibitory segment. Thus, RLC phosphorylation in cardiac muscle may be regulated by two different protein kinases with distinct biochemical regulatory properties.
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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.