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The role of RhoA and Rho-associated kinase in vascular smooth muscle contraction

Swärd, Karl LU ; Mita, Mitsuo ; Wilson, David P ; Deng, Jing Ti ; Susnjar, Marija and Walsh, Michael P (2003) In Current Hypertension Reports 5(1). p.66-72
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... (More)
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. (Less)
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author
; ; ; ; and
publishing date
type
Contribution to journal
publication status
published
subject
in
Current Hypertension Reports
volume
5
issue
1
pages
66 - 72
publisher
Current Medicine Group
external identifiers
  • pmid:12530938
  • scopus:0038351123
ISSN
1534-3111
DOI
10.1007/s11906-003-0013-1
language
English
LU publication?
no
id
636463cf-f01e-4bf3-8b7c-fe82bd182f34 (old id 1126767)
date added to LUP
2016-04-01 12:26:45
date last changed
2022-04-21 07:32:23
@article{636463cf-f01e-4bf3-8b7c-fe82bd182f34,
  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.}},
  author       = {{Swärd, Karl and Mita, Mitsuo and Wilson, David P and Deng, Jing Ti and Susnjar, Marija and Walsh, Michael P}},
  issn         = {{1534-3111}},
  language     = {{eng}},
  number       = {{1}},
  pages        = {{66--72}},
  publisher    = {{Current Medicine Group}},
  series       = {{Current Hypertension Reports}},
  title        = {{The role of RhoA and Rho-associated kinase in vascular smooth muscle contraction}},
  url          = {{http://dx.doi.org/10.1007/s11906-003-0013-1}},
  doi          = {{10.1007/s11906-003-0013-1}},
  volume       = {{5}},
  year         = {{2003}},
}