ArticleAmerican journal of physiology. Cell physiology2008
Myosin light chain kinase activation and calcium sensitization in smooth muscle in vivo.
Article in American journal of physiology. Cell physiology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.
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Who cites it
74 citing papers in PubMed, 113 citations in OpenAlex.
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- Time-of-Day Effects on Post-Activation Potentiation Protocols: Effects of Different Tension Loads on Agility and Vertical Jump Performance in Judokas.Medicina (Kaunas, Lithuania) · 2025Article
- Potential of functional flavonoids in targeting vasospasm through modulation of oxidative stress and SPC-induced signaling pathways.Frontiers in pharmacology · 2025Review
- Filamin A regulates platelet shape change and contractile force generation via phosphorylation of the myosin light chain.The Biochemical journal · 2024Article
- Effects of proton pump inhibitors on inflammatory bowel disease: An updated review.World journal of gastroenterology · 2024Review
- Everolimus-induced hyperpermeability of endothelial cells causes lung injury.Experimental biology and medicine (Maywood, N.J.) · 2023Article
- The Long Noncoding RNA Cardiac Mesoderm Enhancer-Associated Noncoding RNA (Carmn) Is a Critical Regulator of Gastrointestinal Smooth Muscle Contractile Function and Motility.Gastroenterology · 2023Article
- Internalization of apoptotic cells during efferocytosis requires Mertk-mediated calcium influx.Cell death & disease · 2023Article
- Remodeling of the focal adhesion complex by hydrogen-peroxide-induced senescence.Scientific reports · 2023Article
- Long-Term Use of Proton Pump Inhibitors Disrupts Intestinal Tight Junction Barrier and Exaggerates Experimental Colitis.Journal of Crohn's & colitis · 2023Article
- The Role of PKGIα and AMPK Signaling Interplay in the Regulation of Albumin Permeability in Cultured Rat Podocytes.International journal of molecular sciences · 2023Article
- Starving a Cell Promotes Airway Smooth Muscle Relaxation: Inhibition of Glycolysis Attenuates Excitation-Contraction Coupling.American journal of respiratory cell and molecular biology · 2023Article
- The NO/cGMP/PKG pathway in platelets: The therapeutic potential of PDE5 inhibitors in platelet disorders.Journal of thrombosis and haemostasis : JTH · 2022Review
- Nanoparticle Effects on Stress Response Pathways and Nanoparticle-Protein Interactions.International journal of molecular sciences · 2022Review
- Status of Rho kinase inhibitors in glaucoma therapeutics-an overview.International ophthalmology · 2022Review
- Mfge8 attenuates human gastric antrum smooth muscle contractions.Journal of muscle research and cell motility · 2021Article
- Proteome of Stored RBC Membrane and Vesicles from Heterozygous Beta Thalassemia Donors.International journal of molecular sciences · 2021Article
- Thyroxine Induces Acute Relaxation of Rat Skeletal Muscle Arteries via Integrin αvβ3, ERK1/2 and Integrin-Linked Kinase.Frontiers in physiology · 2021Article
14 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 1 institution in 2 countries.
Funding
Abstract
Ca(2+)/calmodulin (CaM)-dependent phosphorylation of myosin regulatory light chain (RLC) in smooth muscle by myosin light chain kinase (MLCK) and dephosphorylation by myosin light chain phosphatase (MLCP) are subject to modulatory cascades that influence the sensitivity of RLC phosphorylation and hence contraction to intracellular Ca(2+) concentration ([Ca(2+)](i)). We designed a CaM-sensor MLCK containing smooth muscle MLCK fused to two fluorescent proteins linked by the MLCK CaM-binding sequence to measure kinase activation in vivo and expressed it specifically in mouse smooth muscle. In phasic bladder muscle, there was greater RLC phosphorylation and force relative to MLCK activation and [Ca(2+)](i) with carbachol (CCh) compared with KCl treatment, consistent with agonist-dependent inhibition of MLCP. The dependence of force on MLCK activity was nonlinear such that at higher concentrations of CCh, force increased with no change in the net 20% activation of MLCK. A significant but smaller amount of MLCK activation was found during the sustained contractile phase. MLCP inhibition may occur through RhoA/Rho-kinase and/or PKC with phosphorylation of myosin phosphatase targeting subunit-1 (MYPT1) and PKC-potentiated phosphatase inhibitor (CPI-17), respectively. CCh treatment, but not KCl, resulted in MYPT1 and CPI-17 phosphorylation. Both Y27632 (Rho-kinase inhibitor) and calphostin C (PKC inhibitor) reduced CCh-dependent force, RLC phosphorylation, and phosphorylation of MYPT1 (Thr694) without changing MLCK activation. Calphostin C, but not Y27632, also reduced CCh-induced phosphorylation of CPI-17. CCh concentration responses showed that phosphorylation of CPI-17 was more sensitive than MYPT1. Thus the onset of agonist-induced contraction in phasic smooth muscle results from the rapid and coordinated activation of MLCK with hierarchical inhibition of MLCP by CPI-17 and MYPT1 phosphorylation.
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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.