Role of serine-threonine phosphoprotein phosphatases in smooth muscle contractility

Trent Butler, Jonathan Paúl, Jonathan Paul, Nick Europe-Finner, Nick Europe‐Finner, Roger Smith, Eng‐Cheng Chan, Eng-Cheng Chan
American journal of physiology. Cell physiology · 2013 · vol. 304(6) , pp. C485–C504 · doi:10.1152/ajpcell.00161.2012 · PMID:23325405 · W2144371871
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This review discusses the role of serine-threonine phosphoprotein phosphatases, particularly MYPT1, in uterine smooth muscle contractility to understand myometrial physiology and develop therapeutics for disorders like dysmenorrhea.

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Abstract

The degree of phosphorylation of myosin light chain 20 (MLC20) is a major determinant of force generation in smooth muscle. Myosin phosphatases (MPs) contain protein phosphatase (PP) 1 as catalytic subunits and are the major enzymes that dephosphorylate MLC20. MP regulatory targeting subunit 1 (MYPT1), the main regulatory subunit of MP in all smooth muscles, is a key convergence point of contractile and relaxatory pathways. Combinations of regulatory mechanisms, including isoform splicing, multiple phosphorylation sites, and scaffolding proteins, modulate MYPT1 activity with tissue and agonist specificities to affect contraction and relaxation. Other members of the PP1 family that do not target myosin, as well as PP2A and PP2B, dephosphorylate a range of proteins that affect smooth muscle contraction. This review discusses the role of phosphatases in smooth muscle contractility with a focus on MYPT1 in uterine smooth muscle. Myometrium shares characteristics of vascular and other visceral smooth muscles yet, during healthy pregnancy, undergoes hypertrophy, hyperplasia, quiescence, and labor as physiological processes. Myometrium presents an accessible model for the study of normal and pathological smooth muscle function, and a better understanding of myometrial physiology may allow the development of novel therapeutics for the many disorders of myometrial physiology from preterm labor to dysmenorrhea.

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Condition tags

dysmenorrhea

MeSH descriptors

Muscle Contraction Muscle, Smooth Myometrium Myosin-Light-Chain Phosphatase Animals Female Humans Ion Channels Ion Channels Mice Muscle, Smooth Muscle, Smooth Myometrium Myometrium Myosin-Light-Chain Phosphatase Myosin Light Chains Myosin Light Chains Myosins Myosins Phosphorylation

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