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Dynamic Regulation of Myosin Light Chain Phosphorylation by Rho-kinase

Myosin light chain (MLC) phosphorylation plays important roles in various cellular functions such as cellular morphogenesis, motility, and smooth muscle contraction. MLC phosphorylation is determined by the balance between activities of Rho-associated kinase (Rho-kinase) and myosin phosphatase. An i...

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Autores principales: Kaneko-Kawano, Takako, Takasu, Fugo, Naoki, Honda, Sakumura, Yuichi, Ishii, Shin, Ueba, Takahiro, Eiyama, Akinori, Okada, Aiko, Kawano, Yoji, Suzuki, Kenji
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3378528/
https://www.ncbi.nlm.nih.gov/pubmed/22723981
http://dx.doi.org/10.1371/journal.pone.0039269
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author Kaneko-Kawano, Takako
Takasu, Fugo
Naoki, Honda
Sakumura, Yuichi
Ishii, Shin
Ueba, Takahiro
Eiyama, Akinori
Okada, Aiko
Kawano, Yoji
Suzuki, Kenji
author_facet Kaneko-Kawano, Takako
Takasu, Fugo
Naoki, Honda
Sakumura, Yuichi
Ishii, Shin
Ueba, Takahiro
Eiyama, Akinori
Okada, Aiko
Kawano, Yoji
Suzuki, Kenji
author_sort Kaneko-Kawano, Takako
collection PubMed
description Myosin light chain (MLC) phosphorylation plays important roles in various cellular functions such as cellular morphogenesis, motility, and smooth muscle contraction. MLC phosphorylation is determined by the balance between activities of Rho-associated kinase (Rho-kinase) and myosin phosphatase. An impaired balance between Rho-kinase and myosin phosphatase activities induces the abnormal sustained phosphorylation of MLC, which contributes to the pathogenesis of certain vascular diseases, such as vasospasm and hypertension. However, the dynamic principle of the system underlying the regulation of MLC phosphorylation remains to be clarified. Here, to elucidate this dynamic principle whereby Rho-kinase regulates MLC phosphorylation, we developed a mathematical model based on the behavior of thrombin-dependent MLC phosphorylation, which is regulated by the Rho-kinase signaling network. Through analyzing our mathematical model, we predict that MLC phosphorylation and myosin phosphatase activity exhibit bistability, and that a novel signaling pathway leading to the auto-activation of myosin phosphatase is required for the regulatory system of MLC phosphorylation. In addition, on the basis of experimental data, we propose that the auto-activation pathway of myosin phosphatase occurs in vivo. These results indicate that bistability of myosin phosphatase activity is responsible for the bistability of MLC phosphorylation, and the sustained phosphorylation of MLC is attributed to this feature of bistability.
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spelling pubmed-33785282012-06-21 Dynamic Regulation of Myosin Light Chain Phosphorylation by Rho-kinase Kaneko-Kawano, Takako Takasu, Fugo Naoki, Honda Sakumura, Yuichi Ishii, Shin Ueba, Takahiro Eiyama, Akinori Okada, Aiko Kawano, Yoji Suzuki, Kenji PLoS One Research Article Myosin light chain (MLC) phosphorylation plays important roles in various cellular functions such as cellular morphogenesis, motility, and smooth muscle contraction. MLC phosphorylation is determined by the balance between activities of Rho-associated kinase (Rho-kinase) and myosin phosphatase. An impaired balance between Rho-kinase and myosin phosphatase activities induces the abnormal sustained phosphorylation of MLC, which contributes to the pathogenesis of certain vascular diseases, such as vasospasm and hypertension. However, the dynamic principle of the system underlying the regulation of MLC phosphorylation remains to be clarified. Here, to elucidate this dynamic principle whereby Rho-kinase regulates MLC phosphorylation, we developed a mathematical model based on the behavior of thrombin-dependent MLC phosphorylation, which is regulated by the Rho-kinase signaling network. Through analyzing our mathematical model, we predict that MLC phosphorylation and myosin phosphatase activity exhibit bistability, and that a novel signaling pathway leading to the auto-activation of myosin phosphatase is required for the regulatory system of MLC phosphorylation. In addition, on the basis of experimental data, we propose that the auto-activation pathway of myosin phosphatase occurs in vivo. These results indicate that bistability of myosin phosphatase activity is responsible for the bistability of MLC phosphorylation, and the sustained phosphorylation of MLC is attributed to this feature of bistability. Public Library of Science 2012-06-19 /pmc/articles/PMC3378528/ /pubmed/22723981 http://dx.doi.org/10.1371/journal.pone.0039269 Text en Kaneko-Kawano et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Kaneko-Kawano, Takako
Takasu, Fugo
Naoki, Honda
Sakumura, Yuichi
Ishii, Shin
Ueba, Takahiro
Eiyama, Akinori
Okada, Aiko
Kawano, Yoji
Suzuki, Kenji
Dynamic Regulation of Myosin Light Chain Phosphorylation by Rho-kinase
title Dynamic Regulation of Myosin Light Chain Phosphorylation by Rho-kinase
title_full Dynamic Regulation of Myosin Light Chain Phosphorylation by Rho-kinase
title_fullStr Dynamic Regulation of Myosin Light Chain Phosphorylation by Rho-kinase
title_full_unstemmed Dynamic Regulation of Myosin Light Chain Phosphorylation by Rho-kinase
title_short Dynamic Regulation of Myosin Light Chain Phosphorylation by Rho-kinase
title_sort dynamic regulation of myosin light chain phosphorylation by rho-kinase
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3378528/
https://www.ncbi.nlm.nih.gov/pubmed/22723981
http://dx.doi.org/10.1371/journal.pone.0039269
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