ArticleThe Journal of biological chemistry2009
Phosphorylation-dependent autoinhibition of myosin light chain phosphatase accounts for Ca2+ sensitization force of smooth muscle contraction.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
72 citing papers in PubMed, 103 citations in OpenAlex.
- Advances in Understanding Calcium Sensitization in Gastrointestinal Smooth Muscles: Pathways, Interstitial Cells, and Disease.Journal of neurogastroenterology and motility · 2026Review
- The sphingosine-1-phosphate pathway is differentially activated in human gestational tissues.Journal of the Endocrine Society · 2026Article
- Steady-state epithelial apical flatness is characterized by MLCK morphodynamics and asynchronous CaMolecular biology of the cell · 2026Article
- HuangE Capsules Improve Bladder Function in BOO-induced Overactive Bladder Rats: Network Pharmacology and Experimental Validation.Combinatorial chemistry & high throughput screening · 2026Article
- Unresolved mechanisms: a hypothesized spatial regulation of myosin light chain phosphorylation within the walls of resistance arteries.Frontiers in physiology · 2026Article
- Soy isoflavone yeast fermented extract inhibits contraction of rat ileal smooth muscle via opening of KThe Journal of veterinary medical science · 2025Article
- LUZP1 regulates the maturation of contractile actomyosin bundles.Cellular and molecular life sciences : CMLS · 2024Article
- Pulses of RhoA signaling stimulate actin polymerization and flow in protrusions to drive collective cell migration.Current biology : CB · 2024Article
- Pulses of RhoA Signaling Stimulate Actin Polymerization and Flow in Protrusions to Drive Collective Cell Migration.bioRxiv : the preprint server for biology · 2023Article
- Serine/Threonine Protein Phosphatases 1 and 2A in Lung Endothelial Barrier Regulation.Biomedicines · 2023Review
- Phosphorylated Peptide Derived from the Myosin Phosphatase Target Subunit Is a Novel Inhibitor of Protein Phosphatase-1.International journal of molecular sciences · 2023Article
- Dual thick and thin filament linked regulation of stretch- and L-NAME-induced tone in young and senescent murine basilar artery.Frontiers in physiology · 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
- MARK2 regulates directed cell migration through modulation of myosin II contractility and focal adhesion organization.Current biology : CB · 2022Article
- Identification of the Kinase-Substrate Recognition Interface between MYPT1 and Rho-Kinase.Biomolecules · 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
- The lipid phosphatase-like protein PLPPR1 associates with RhoGDI1 to modulate RhoA activation in response to axon growth inhibitory molecules.Journal of neurochemistry · 2021Article
- The mechanism of electroacupuncture for treating spinal cord injury rats by mediating Rho/Rho-associated kinase signaling pathway.The journal of spinal cord medicine · 2021Article
- EPAC in Vascular Smooth Muscle Cells.International journal of molecular sciences · 2020Review
12 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
The reversible regulation of myosin light chain phosphatase (MLCP) in response to agonist stimulation and cAMP/cGMP signals plays an important role in the regulation of smooth muscle (SM) tone. Here, we investigated the mechanism underlying the inhibition of MLCP induced by the phosphorylation of myosin phosphatase targeting subunit (MYPT1), a regulatory subunit of MLCP, at Thr-696 and Thr-853 using glutathione S-transferase (GST)-MYPT1 fragments having the inhibitory phosphorylation sites. GST-MYPT1 fragments, including only Thr-696 and only Thr-853, inhibited purified MLCP (IC(50) = 1.6 and 60 nm, respectively) when they were phosphorylated with RhoA-dependent kinase (ROCK). The activities of isolated catalytic subunits of type 1 and type 2A phosphatases (PP1 and PP2A) were insensitive to either fragment. Phospho-GST-MYPT1 fragments docked directly at the active site of MLCP, and this was blocked by a PP1/PP2A inhibitor microcystin (MC)-LR or by mutation of the active sites in PP1. GST-MYPT1 fragments induced a contraction of beta-escin-permeabilized ileum SM at constant pCa 6.3 (EC(50) = 2 microm), which was eliminated by Ala substitution of the fragment at Thr-696 or by ROCK inhibitors or 8Br-cGMP. GST-MYPT1-(697-880) was 5-times less potent than fragments including Thr-696. Relaxation induced by 8Br-cGMP was not affected by Ala substitution at Ser-695, a known phosphorylation site for protein kinase A/G. Thus, GST-MYPT1 fragments are phosphorylated by ROCK in permeabilized SM and mimic agonist-induced inhibition and cGMP-induced activation of MLCP. We propose a model in which MYPT1 phosphorylation at Thr-696 and Thr-853 causes an autoinhibition of MLCP that accounts for Ca(2+) sensitization of smooth muscle force.
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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.