ArticleMolecular human reproduction2012
Phasic contractions of isolated human myometrium are associated with Rho-kinase (ROCK)-dependent phosphorylation of myosin phosphatase-targeting subunit (MYPT1).
Article in Molecular human reproduction, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 45 citations in OpenAlex.
- Failed induction of human labour is associated with an altered myometrial phosphoproteome.Scientific reports · 2025Article
- Assessing Tocolytic Potency: Variability and Accuracy of AUC Versus Amplitude-Based Assessment of Pregnant Human Myometrial Contractions Ex Vivo.Reproductive sciences (Thousand Oaks, Calif.) · 2025Article
- The role of the RHOA/ROCK pathway in the regulation of myometrial stages throughout pregnancy.AJOG global reports · 2024Article
- Assessing the Potency of the Novel Tocolytics 2-APB, Glycyl-H-1152, and HC-067047 in Pregnant Human Myometrium.Reproductive sciences (Thousand Oaks, Calif.) · 2023Article
- Implications of the RhoA/Rho associated kinase pathway and leptin in primary uterine inertia in the dog.The Journal of reproduction and development · 2021Article
- Repurposing simvastatin as a therapy for preterm labor: evidence from preclinical models.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- Misleading Westerns: Common Quantification Mistakes in Western Blot Densitometry and Proposed Corrective Measures.BioMed research international · 2019Article
- Retracted Article: MiR-182-5p and miR-96-5p increased hepatocellular carcinoma cell mobility, proliferation and cisplatin resistance partially by targeting RND3.RSC advances · 2018Article
- Overexpression of Myosin Phosphatase Target Subunit 1 (MYPT1) Inhibits Tumor Progression and Metastasis of Gastric Cancer.Medical science monitor : international medical journal of experimental and clinical research · 2018Article
- Petri net-based prediction of therapeutic targets that recover abnormally phosphorylated proteins in muscle atrophy.BMC systems biology · 2018Article
- Relaxant and anti-inflammatory effect of two thalidomide analogs as PDE-4 inhibitors in pregnant rat uterus.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2017Article
- Vascular smooth muscle cell glycocalyx mediates shear stress-induced contractile responses via a Rho kinase (ROCK)-myosin light chain phosphatase (MLCP) pathway.Scientific reports · 2017Article
- Modulation of Progesterone Receptor Isoform Expression in Pregnant Human Myometrium.BioMed research international · 2017Article
- The expression of genes involved in myometrial contractility changes during ex situ culture of pregnant human uterine smooth muscle tissue.Journal of smooth muscle research = Nihon Heikatsukin Gakkai kikanshi · 2017Article
- Differential impact of acute and prolonged cAMP agonist exposure on protein kinase A activation and human myometrium contractile activity.The Journal of physiology · 2016Article
- Inhibition of Uterine Contractility by Thalidomide Analogs via Phosphodiesterase-4 Inhibition and Calcium Entry Blockade.Molecules (Basel, Switzerland) · 2016Article
- Altered Expression of Human Smooth Muscle Myosin Phosphatase Targeting (MYPT) Isovariants with Pregnancy and Labor.PloS one · 2016Article
- In vivo roles for myosin phosphatase targeting subunit-1 phosphorylation sites T694 and T852 in bladder smooth muscle contraction.The Journal of physiology · 2015Article
- Article
- Lesions from patients with sporadic cerebral cavernous malformations harbor somatic mutations in the CCM genes: evidence for a common biochemical pathway for CCM pathogenesis.Human molecular genetics · 2014Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Force generation in smooth muscle is driven by phosphorylation of myosin light chains (MYL), which is regulated by the equilibrium between the activities of myosin light chain kinase (MYLK) and myosin phosphatase (MYLP). MYLK is activated by Ca(2+)-calmodulin whereas MYLP is inhibited by phosphorylation of its myosin-binding subunit (MYPT1) by Ca(2+)-independent mechanisms, leading to generation of increased MYL phosphorylation and force for a given intracellular Ca(2+) concentration, a phenomenon known as 'calcium-sensitization'. The regulation of MYPT1 phosphorylation in human myometrium, which shows increasing phasic contractility at the onset of labour, has yet to be fully investigated. Here, we explore phosphorylation of MYPT1 at Thr696 and Thr853, alongside phosphorylation of MYL, in fresh human myometrial tissue and cultured myometrial cells. We report that pMYPT1 (Thr853) levels are dependent on the activity of Rho-associated kinase (ROCK), determined using the ROCK inhibitor g-H-1152 and siRNA-mediated knockdown of ROCK1/2, and are highly correlated to ppMYL (Thr18/Ser19) levels. Pharmacological inhibition of ROCK was associated with a decrease in oxytocin (OXT)-stimulated contractility of myometrial strips in vitro. Moreover, we have measured pMYPT1 and pMYL levels between and during spontaneous and OXT-stimulated phasic contractions by rapidly freezing contracting muscle, and demonstrate for the first time functional coupling between increases in pMYPT1 (Thr853), ppMYL (Thr18/Ser19) and phasic contractility that is ROCK-dependent. The combined approach of measuring contractility and phosphorylation has demonstrated that the phosphorylation of MYPT1 (Thr853) changes dynamically with each contraction and has elucidated a defined role for ROCK in regulating myometrial contractility through MYLP, providing new insights into uterine physiology which will stimulate further research into treatments for preterm labour.
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