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:	Takako Kaneko-Kawano, Fugo Takasu, Honda Naoki, Yuichi Sakumura, Shin Ishii, Takahiro Ueba, Akinori Eiyama, Aiko Okada, Yoji Kawano, Kenji Suzuki
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9965a0951df04d17b50db4c9784ddbcf
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spelling	oai:doaj.org-article:9965a0951df04d17b50db4c9784ddbcf2021-11-18T07:14:58ZDynamic regulation of myosin light chain phosphorylation by Rho-kinase.1932-620310.1371/journal.pone.0039269https://doaj.org/article/9965a0951df04d17b50db4c9784ddbcf2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22723981/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Myosin 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.Takako Kaneko-KawanoFugo TakasuHonda NaokiYuichi SakumuraShin IshiiTakahiro UebaAkinori EiyamaAiko OkadaYoji KawanoKenji SuzukiPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 6, p e39269 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Takako Kaneko-Kawano Fugo Takasu Honda Naoki Yuichi Sakumura Shin Ishii Takahiro Ueba Akinori Eiyama Aiko Okada Yoji Kawano Kenji Suzuki Dynamic regulation of myosin light chain phosphorylation by Rho-kinase.
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.
format	article
author	Takako Kaneko-Kawano Fugo Takasu Honda Naoki Yuichi Sakumura Shin Ishii Takahiro Ueba Akinori Eiyama Aiko Okada Yoji Kawano Kenji Suzuki
author_facet	Takako Kaneko-Kawano Fugo Takasu Honda Naoki Yuichi Sakumura Shin Ishii Takahiro Ueba Akinori Eiyama Aiko Okada Yoji Kawano Kenji Suzuki
author_sort	Takako Kaneko-Kawano
title	Dynamic regulation of myosin light chain phosphorylation by Rho-kinase.
title_short	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_sort	dynamic regulation of myosin light chain phosphorylation by rho-kinase.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/9965a0951df04d17b50db4c9784ddbcf
work_keys_str_mv	AT takakokanekokawano dynamicregulationofmyosinlightchainphosphorylationbyrhokinase AT fugotakasu dynamicregulationofmyosinlightchainphosphorylationbyrhokinase AT hondanaoki dynamicregulationofmyosinlightchainphosphorylationbyrhokinase AT yuichisakumura dynamicregulationofmyosinlightchainphosphorylationbyrhokinase AT shinishii dynamicregulationofmyosinlightchainphosphorylationbyrhokinase AT takahiroueba dynamicregulationofmyosinlightchainphosphorylationbyrhokinase AT akinorieiyama dynamicregulationofmyosinlightchainphosphorylationbyrhokinase AT aikookada dynamicregulationofmyosinlightchainphosphorylationbyrhokinase AT yojikawano dynamicregulationofmyosinlightchainphosphorylationbyrhokinase AT kenjisuzuki dynamicregulationofmyosinlightchainphosphorylationbyrhokinase
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Dynamic regulation of myosin light chain phosphorylation by Rho-kinase.

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