Rho‐kinase/ROCK: A key regulator of the cytoskeleton and cell polarity

Abstract

Rho‐associated kinase (Rho‐kinase/ROCK/ROK) is an effector of the small GTPase Rho and belongs to the AGC family of kinases. Rho‐kinase has pleiotropic functions including the regulation of cellular contraction, motility, morphology, polarity, cell division, and gene expression. Pharmacological analyses have revealed that Rho‐kinase is involved in a wide range of diseases such as vasospasm, pulmonary hypertension, nerve injury, and glaucoma, and is therefore considered to be a potential therapeutic target. This review focuses on the structure, function, and modes of activation and action of Rho‐kinase. © 2010 Wiley‐Liss, Inc.

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    Not in our library10.1097/00005344-200312001-00011

89. 89.

    Shimizu T, Ihara K, Maesaki R, Amano M, Kaibuchi K, Hakoshima T. Parallel coiled-coil association of the RhoA-binding domain in Rho-kinase. J Biol Chem. 2003;278:46046-46051.

    Not in our library10.1074/jbc.m306458200

90. 90.

    Shimizu Y, Thumkeo D, Keel J, Ishizaki T, Oshima H, Oshima M, Noda Y, Matsumura F, Taketo MM, Narumiya S. ROCK-I regulates closure of the eyelids and ventral body wall by inducing assembly of actomyosin bundles. J Cell Biol. 2005;168:941-953.

    Not in our library10.1083/jcb.200411179

91. 91.

    Shimokawa H, Rashid M. Development of Rho-kinase inhibitors for cardiovascular medicine. Trends Pharmacol Sci. 2007;28:296-302.

    Not in our library10.1016/j.tips.2007.04.006

92. 92.

    Sugimoto M, Nakayama M, Goto TM, Amano M, Komori K, Kaibuchi K. Rho-kinase phosphorylates eNOS at threonine 495 in endothelial cells. Biochemi Biophys Res Commun. 2007;361:462-467.

    Not in our library10.1016/j.bbrc.2007.07.030

93. 93.

    Svoboda KK, Moessner P, Field T, Acevedo J. ROCK inhibitor (Y27632) increases apoptosis and disrupts the actin cortical mat in embryonic avian corneal epithelium. Dev Dyn. 2004;229:579-590.

    Not in our library10.1002/dvdy.20008

94. 94.

    Takefuji M, Mori K, Morita Y, Arimura N, Nishimura T, Nakayama M, Hoshino M, Iwamatsu A, Murohara T, Kaibuchi K, Amano M. Rho-kinase modulates the function of STEF, a Rac GEF, through its phosphorylation. Biochem Biophys Res Commun. 2007;355:788-794.

    Not in our library10.1016/j.bbrc.2007.02.028

95. 95.

    Tanaka T, Nishimura D, Wu RC, Amano M, Iso T, Kedes L, Nishida H, Kaibuchi K, Hamamori Y. Nuclear Rho kinase, ROCK2, targets p300 acetyltransferase. J Biol Chem. 2006;281:15320-15329.

    Not in our library10.1074/jbc.m510954200

96. 96.

    Tang BL, Liou YC. Novel modulators of amyloid-beta precursor protein processing. J Neurochem. 2007;100:314-323.

    Not in our library10.1111/j.1471-4159.2006.04215.x

97. 97.

    Thumkeo D, Keel J, Ishizaki T, Hirose M, Nonomura K, Oshima H, Oshima M, Taketo MM, Narumiya S. Targeted disruption of the mouse rho-associated kinase 2 gene results in intrauterine growth retardation and fetal death. Mol Cell Biol. 2003;23:5043-5055.

    Not in our library10.1128/mcb.23.14.5043-5055.2003

98. 98.

    Thumkeo D, Shimizu Y, Sakamoto S, Yamada S, Narumiya S. ROCK-I and ROCK-II cooperatively regulate closure of eyelid and ventral body wall in mouse embryo. Genes Cells. 2005;10:825-834.

    Not in our library10.1111/j.1365-2443.2005.00882.x

99. 99.

    Tominaga T, Barber DL. Na-H exchange acts downstream of RhoA to regulate integrin-induced cell adhesion and spreading. Mol Biol Cell. 1998;9:2287-2303.

    Not in our library10.1091/mbc.9.8.2287

100. 100.

     Totsukawa G, Wu Y, Sasaki Y, Hartshorne DJ, Yamakita Y, Yamashiro S, Matsumura F. Distinct roles of MLCK and ROCK in the regulation of membrane protrusions and focal adhesion dynamics during cell migration of fibroblasts. J Cell Biol. 2004;164:427-439.

     Not in our library10.1083/jcb.200306172

101. 101.

     Uehata M, Ishizaki T, Satoh H, Ono T, Kawahara T, Morishita T, Tamakawa H, Yamagami K, Inui J, Maekawa M, Narumiya S. Calcium sensitization of smooth muscle mediated by a Rho-associated protein kinase in hypertension. Nature. 1997;389:990-994.

     Not in our library10.1038/40187

102. 102.

     Vahebi S, Kobayashi T, Warren CM, de Tombe PP, Solaro RJ. Functional effects of rho-kinase-dependent phosphorylation of specific sites on cardiac troponin. Circ Res. 2005;96:740-747.

     Not in our library10.1161/01.res.0000162457.56568.7d

103. 103.

     Wang Y, Zheng XR, Riddick N, Bryden M, Baur W, Zhang X, Surks HK. ROCK isoform regulation of myosin phosphatase and contractility in vascular smooth muscle cells. Circ Res. 2009;104:531-540.

     Not in our library10.1161/circresaha.108.188524

104. 104.

     Ward Y, Yap SF, Ravichandran V, Matsumura F, Ito M, Spinelli B, Kelly K. The GTP binding proteins Gem and Rad are negative regulators of the Rho-Rho kinase pathway. J Cell Biol. 2002;157:291-302.

     Not in our library10.1083/jcb.200111026

105. 105.

     Watanabe N, Kato T, Fujita A, Ishizaki T, Narumiya S. Cooperation between mDia1 and ROCK in Rho-induced actin reorganization. Nat Cell Biol. 1999;1:136-143.

     Not in our library10.1038/11056

106. 106.

     Watanabe K, Ueno M, Kamiya D, Nishiyama A, Matsumura M, Wataya T, Takahashi JB, Nishikawa S, Nishikawa S, Muguruma K, Sasai Y. A ROCK inhibitor permits survival of dissociated human embryonic stem cells. Nat Biotechnol. 2007;25:681-686.

     Not in our library10.1038/nbt1310

107. 107.

     Winter CG, Wang B, Ballew A, Royou A, Karess R, Axelrod JD, Luo L. Drosophila Rho-associated kinase (Drok) links Frizzled-mediated planar cell polarity signaling to the actin cytoskeleton. Cell. 2001;105:81-91.

     Not in our library10.1016/s0092-8674(01)00298-7

108. 108.

     Worthylake RA, Lemoine S, Watson JM, Burridge K. RhoA is required for monocyte tail retraction during transendothelial migration. J Cell Biol. 2001;154:147-160.

     Not in our library10.1083/jcb.200103048

109. 109.

     Xu J, Wang F, Van Keymeulen A, Herzmark P, Straight A, Kelly K, Takuwa Y, Sugimoto N, Mitchison T, Bourne HR. Divergent signals and cytoskeletal assemblies regulate self-organizing polarity in neutrophils. Cell. 2003;114:201-214.

     Not in our library10.1016/s0092-8674(03)00555-5

110. 110.

     Yamaguchi H, Kasa M, Amano M, Kaibuchi K, Hakoshima T. Molecular mechanism for the regulation of rho-kinase by dimerization and its inhibition by fasudil. Structure. 2006a;14:589-600.

     Not in our library10.1016/j.str.2005.11.024

111. 111.

     Yamaguchi H, Miwa Y, Kasa M, Kitano K, Amano M, Kaibuchi K, Hakoshima T. Structural basis for induced-fit binding of Rho-kinase to the inhibitor Y-27632. J Biochem. 2006b;140:305-311.

     Not in our library10.1093/jb/mvj172

112. 112.

     Yasui Y, Amano M, Nagata K, Inagaki N, Nakamura H, Saya H, Kaibuchi K, Inagaki M. Roles of Rho-associated kinase in cytokinesis; mutations in Rho-associated kinase phosphorylation sites impair cytokinetic segregation of glial filaments. J Cell Biol. 1998;143:1249-1258.

     Not in our library10.1083/jcb.143.5.1249

113. 113.

     Yoneda A, Multhaupt HA, Couchman JR. The Rho kinases I and II regulate different aspects of myosin II activity. J Cell Biol. 2005;170:443-453.

     Not in our library10.1083/jcb.200412043

114. 114.

     Zhou Y, Su Y, Li B, Liu F, Ryder JW, Wu X, Gonzalez-DeWhitt PA, Gelfanova V, Hale JE, May PC, Paul SM, Ni B. Nonsteroidal anti-inflammatory drugs can lower amyloidogenic Abeta42 by inhibiting Rho. Science. 2003;302:1215-1217.

     Not in our library10.1126/science.1090154

Cited by papers we hold 23

• Microglia Mediated Neuroinflammation in Parkinson’s Disease · 2023
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• Cellular mechanotransduction in health and diseases: from molecular mechanism to therapeutic targets · 2023
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• Collagen I triggers directional migration, invasion and matrix remodeling of stroma cells in a 3D spheroid model of endometriosis · 2021
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• Microglia jointly degrade fibrillar alpha-synuclein cargo by distribution through tunneling nanotubes · 2021
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• RhoA-ROCK Signaling as a Therapeutic Target in Traumatic Brain Injury · 2020
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• Mechanical tumor microenvironment and transduction: cytoskeleton mediates cancer cell invasion and metastasis · 2020
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• Sterol regulatory element binding protein 1 couples mechanical cues and lipid metabolism · 2019
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• LncRNAs regulate the cytoskeleton and related Rho/ROCK signaling in cancer metastasis · 2018
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• Mechanotransduction and cell biomechanics of the intervertebral disc · 2018
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• Aberrant T Cell Signaling and Subsets in Systemic Lupus Erythematosus · 2018
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• YAP regulates cell mechanics by controlling focal adhesion assembly · 2017
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• YAP is essential for mechanical force production and epithelial cell proliferation during lung branching morphogenesis · 2017
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• Long non-coding RNA MALAT1 for promoting metastasis and proliferation by acting as a ceRNA of miR-144-3p in osteosarcoma cells · 2017
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• Effect of shear stress on iPSC-derived human brain microvascular endothelial cells (dhBMECs) · 2017
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• The Soft- and Hard-Heartedness of Cardiac Fibroblasts: Mechanotransduction Signaling Pathways in Fibrosis of the Heart · 2017
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• Mechanical cell competition kills cells via induction of lethal p53 levels · 2016
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• Novel Insights into the Roles of Rho Kinase in Cancer · 2016
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• Mechanical stress regulates gene expression via Rho/Rho-kinase signaling pathway · 2015
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• Gene expression profiling reveals potential prognostic biomarkers associated with the progression of heart failure · 2015
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• Rho GTPases and regulation of cell migration and polarization in human corneal epithelial cells. · 2013
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and 3 more

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