Regulation of Myosin Phosphatase by Rho and Rho-Associated Kinase (Rho-Kinase)

Kimura, Kei; M, Ito; Amano, Mutsuki; Chihara, Kazuyasu; Fukata, Yuko; Nakafuku, Masato; Yamamori, Bunpei; Feng, Jianhua; Nakano, Takeshi; Okawa, Katsuya; Iwamatsu, Akihiro; Kaibuchi, Kozo

doi:10.1126/science.273.5272.245

Cited by 2,647 publications

(2,199 citation statements)

References 28 publications

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“…ROCK activates myosin light-chain kinase by phosphorylation of the myosin-binding subunit in myosin light-chain phosphatase, leading to contraction of vascular smooth muscle cells. 97,98 Indeed, the RhoA/ROCK pathway has been shown to be involved in the formation of atherosclerotic lesions, vasoconstriction and myocardial hypertrophy and to be activated in patients with hypertension and in patients with coronary artery disease. [99][100][101][102][103][104] Recently, we have shown that FMD is an independent predictor of leukocyte ROCK activity in healthy men and men with cardiovascular risk factors but without established cardiovascular or cerebrovascular diseases, suggesting that cumulative cardiovascular risk, including aging and hypertension, may enhance ROCK activity and endothelial dysfunction.…”

Section: Tetrahydrobiopterin (Bh 4 )mentioning

confidence: 99%

Endothelial dysfunction and hypertension in aging

2012

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Hypertension is one of the common diseases in the elderly. The prevalence of hypertension markedly increases with advancing age. Both aging and hypertension have a critical role in cardiovascular and cerebrovascular complications. Although aging and hypertension, either independently or collectively, impair endothelial function, aging and hypertension may have similar cascades for the pathogenesis and development of endothelial dysfunction. Nitric oxide (NO) has an important role in regulation of vascular tone. Decrease in NO bioavailability by endothelial dysfunction would lead to elevation of blood pressure. An imbalance of reduced production of NO or increased production of reactive oxygen species, mainly superoxide, may promote endothelial dysfunction. One possible mechanism by which the prevalence of hypertension is increased in relation to aging may be advancing endothelial dysfunction associated with aging through an increase in oxidative stress. In addition, endothelial cell senescence is also involved in aging-related endothelial dysfunction. In this review, we focus on recent findings and interactions between endothelial function, oxidative stress and hypertension in aging.

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Section: Tetrahydrobiopterin (Bh 4 )mentioning

confidence: 99%

Endothelial dysfunction and hypertension in aging

2012

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“…Signaling through its effectors Rho kinase (ROCK) and mDia, Rho stimulates actin stress fiber formation by stimulating the monomeric actin binding protein profilin, and stabilizes stress fibers by inhibiting the activity of the actin depolymerizing protein, cofilin [35][36][37][38][39][40]. Bundling of actin filaments with myosin to form stress fibers, itself stimulated by ROCK and myosin light chain kinase, stimulates cell contraction and stabilization of focal adhesions [41][42][43][44], points of integrin-extracellular matrix contact between the ventral surface of the cell and the underlying substrate. Rho-mediated contractility is important for retraction of the cell rear and translocation of the cell body [26].…”

Section: Rho Family Gtpases Regulate Actin Dynamicsmentioning

confidence: 99%

“…Activation of Rho stimulates contractility and focal adhesion formation by promoting bundling of actin filaments and associated myosin motors into stress fibers [44]. Rho-ROCK signaling influences contraction through effects on both the myosin and actin: ROCK elevates myosin light chain phosphorylation by inhibiting myosin phosphatase and/or by directly phosphorylating myosin light chain (MLC) [41][42][43]. ROCK also phosphorylates and activates LIM kinase [64], which in turn phosphorylates and inactivates the actin severing protein, cofilin [36,65].…”

Section: Focal Adhesion Dynamicsmentioning

confidence: 99%

Scaffold mediated regulation of MAPK signaling and cytoskeletal dynamics: A perspective

Pullikuth

Catling

2007

Cellular Signalling

135

107

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Cell migration is critical for many physiological processes and is often misregulated in developmental disorders and pathological conditions including cancer and neurodegeneration. MAPK signaling and the Rho family of proteins are known regulators of cell migration that exert their influence on cellular cytoskeleton during cell adhesion and migration. Here we review data supporting the view that localized ERK signaling mediated through recently identified scaffold proteins may regulate cell migration.

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“…ROCK phosphorylates and inactivates myosin phosphatase, linking rho to effects on smooth muscle contraction (Kimura et al 1996). ROCK is also involved in the regulation of stress fibers by rho, as microinjection of the catalytic domain of ROCK causes stress fiber formation (Amano et al 1997).…”

Section: Rho Gtpases: Organizers Of Actin Structuresmentioning

confidence: 99%

Signaling mechanisms that regulate actin‐based motility processes in the nervous system

Meyer

Feldman

2002

Journal of Neurochemistry

170

108

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Actin-based motility is critical for nervous system development. Both the migration of neurons and the extension of neurites require organized actin polymerization to push the cell membrane forward. Numerous extracellular stimulants of motility and axon guidance cues regulate actin-based motility through the rho GTPases (rho, rac, and cdc42). The rho GTPases reorganize the actin cytoskeleton, leading to stress fiber, filopodium, or lamellipodium formation. The activity of the rho GTPases is regulated by a variety of proteins that either stimulate GTP uptake (activation) or hydrolysis (inactivation). These proteins potentially link extracellular signals to the activation state of rho GTPases. Effectors downstream of the rho GTPases that directly influence actin polymerization have been identified and are involved in neurite development.The Arp2/3 complex nucleates the formation of new actin branches that extend the membrane forward. Ena/VASP proteins can cause the formation of longer actin filaments, characteristic of growth cone actin morphology, by preventing the capping of barbed ends. Actin-depolymerizing factor (ADF)/cofilin depolymerizes and severs actin branches in older parts of the actin meshwork, freeing monomers to be re-incorporated into actively growing filaments. The signaling mechanisms by which extracellular cues that guide axons to their targets lead to direct effects on actin filament dynamics are becoming better understood. Keywords: actin-depolymerizing factor (ADF)/cofilin, actinrelated protein Arp2/3, ena/VASP, LIM kinase, rho GTPase.

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Regulation of Myosin Phosphatase by Rho and Rho-Associated Kinase (Rho-Kinase)

Cited by 2,647 publications

References 28 publications

Endothelial dysfunction and hypertension in aging

Endothelial dysfunction and hypertension in aging

Scaffold mediated regulation of MAPK signaling and cytoskeletal dynamics: A perspective

Signaling mechanisms that regulate actin‐based motility processes in the nervous system

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