Please use this identifier to cite or link to this item: https://hdl.handle.net/2440/39083
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Type: Journal article
Title: The role of RhoA and Rho-associated kinase in vascular smooth muscle contraction
Author: Sward, K.
Mita, M.
Wilson, D.
Deng, J.
Susnjar, M.
Walsh, M.
Citation: Current Hypertension Reports, 2003; 5(1):66-72
Publisher: Current Science Inc.
Issue Date: 2003
ISSN: 1522-6417
1534-3111
Statement of
Responsibility: 
Karl Swärd, Mitsuo Mita, David P. Wilson, Jing Ti Deng, Marija Susnjar and Michael P. Walsh
Abstract: A variety of contractile agonists trigger activation of the small GTPase RhoA. An important target of activated RhoA in smooth muscle is Rho-associated kinase (ROK), one of the downstream targets that is the myosin binding subunit (MYPT1) of myosin light chain phosphatase (MLCP). Phosphorylation of MYPT1 at T695 by activated ROK results in a decrease in phosphatase activity of MLCP and an increase in myosin light chain (LC(20)) phosphorylation catalyzed by Ca(2)(+)/calmodulin-dependent myosin light chain kinase and/or a distinct Ca(2)(+)-independent kinase. LC(20) phosphorylation in turn triggers cross-bridge cycling and force development. ROK also phosphorylates the cytosolic protein CPI-17 (at T38), which thereby becomes a potent inhibitor of MLCP. The RhoA/ROK pathway has been implicated in the tonic phase of force maintenance in response to various agonists, with no evident role in the phasic response, suggesting this pathway as a potential target for antihypertensive therapy. Indeed, ROK inhibitors restore normal blood pressure in several rat hypertensive models.
Keywords: Muscle, Smooth, Vascular
Animals
Humans
Hypertension
Calcium
rhoA GTP-Binding Protein
Myosin-Light-Chain Phosphatase
Protein-Serine-Threonine Kinases
Intracellular Signaling Peptides and Proteins
Signal Transduction
Phosphorylation
Muscle Contraction
Phosphoprotein Phosphatases
rho-Associated Kinases
Rights: © 2003 by Current Science Inc.
DOI: 10.1007/s11906-003-0013-1
Published version: http://www.springerlink.com/content/t62180n084222268/
Appears in Collections:Aurora harvest
Molecular and Biomedical Science publications

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