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Science 19 November 1999: Vol. 286. no. 5444, pp. 1583 - 1587 DOI: 10.1126/science.286.5444.1583
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Reports
Regulation of Myosin Phosphatase by a Specific Interaction with cGMP- Dependent Protein Kinase I
Howard K. Surks,
1
Naoki Mochizuki,
12
Yasuyo Kasai,
1
Serban P. Georgescu,
1
K. Mary Tang,
1
Masaaki Ito,
3
Thomas M. Lincoln,
4
Michael E. Mendelsohn
1*
Contraction and relaxation of smooth muscle are
regulated by myosin light-chain kinase and myosin phosphatase through
phosphorylation and dephosphorylation of myosin
light chains. Cyclic guanosine monophosphate (cGMP)-dependent protein
kinase I (cGKI ) mediates physiologic relaxation of vascular
smooth muscle in response to nitric oxide and cGMP. It is shown here
that cGKI is targeted to the smooth muscle cell contractile
apparatus by a leucine zipper interaction with the myosin-binding
subunit (MBS) of myosin phosphatase. Uncoupling of the cGKI -MBS
interaction prevents cGMP-dependent dephosphorylation of
myosin light chain, demonstrating that this interaction is essential to
the regulation of vascular smooth muscle cell tone.
1 Molecular Cardiology Research Institute and
Cardiology Division, Department of Medicine, Tufts University School of
Medicine and New England Medical Center, Boston, MA 02111, USA.
2 Department of Pathology, Research Institute,
International Medical Center of Japan, Tokyo 162-8655, Japan.
3 First Department of Internal Medicine, Mie
University School of Medicine, Tsu 514, Japan.
4 Department of Pathology, Division of Molecular and
Cellular Pathology, University of Alabama, Birmingham, AL 35294-0019,
USA.
*
To whom correspondence should be addressed. E-mail:
mmendelsohn{at}lifespan.org
Read the Full Text
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- Differential relaxing responses to particulate or soluble guanylyl cyclase activation on endothelial cells: a mechanism dependent on PKG-I{alpha} activation by NO/cGMP.
- F. J. Rivero-Vilches, S De Frutos, M Saura, D Rodriguez-Puyol, and M Rodriguez-Puyol (2003)
Am J Physiol Cell Physiol
285, C891-C898
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- Cyclic GMP Phosphodiesterases and Regulation of Smooth Muscle Function.
- S. D. Rybalkin, C. Yan, K. E. Bornfeldt, and J. A. Beavo (2003)
Circ. Res.
93, 280-291
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- Invited Review: Do inflammatory mediators influence the contribution of airway smooth muscle contraction to airway hyperresponsiveness in asthma?.
- D. J. Fernandes, R. W. Mitchell, O. Lakser, M. Dowell, A. G. Stewart, and J. Solway (2003)
J Appl Physiol
95, 844-853
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- Hypoxia enhances a cGMP-independent nitric oxide relaxing mechanism in pulmonary arteries.
- C. J. Mingone, S. A. Gupte, T. Iesaki, and M. S. Wolin (2003)
Am J Physiol Lung Cell Mol Physiol
285, L296-L304
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- Nitric Oxide-Induced Decrease in Calcium Sensitivity of Resistance Arteries Is Attributable to Activation of the Myosin Light Chain Phosphatase and Antagonized by the RhoA/Rho Kinase Pathway.
- S.-S. Bolz, L. Vogel, D. Sollinger, R. Derwand, C. de Wit, G. Loirand, and U. Pohl (2003)
Circulation
107, 3081-3087
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- Inhibition of sustained smooth muscle contraction by PKA and PKG preferentially mediated by phosphorylation of RhoA.
- K. S. Murthy, H. Zhou, J. R. Grider, and G. M. Makhlouf (2003)
Am J Physiol Gastrointest Liver Physiol
284, G1006-G1016
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- ERK and RhoA Differentially Regulate Pseudopodia Growth and Retraction during Chemotaxis.
- A. A. Brahmbhatt and R. L. Klemke (2003)
J. Biol. Chem.
278, 13016-13025
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- Regulation of Estrogen Receptor alpha -mediated Transcription by a Direct Interaction with Protein Phosphatase 2A.
- Q. Lu, H. K. Surks, H. Ebling, W. E. Baur, D. Brown, D. C. Pallas, and R. H. Karas (2003)
J. Biol. Chem.
278, 4639-4645
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- Selective phosphorylation of the IP3R-I in vivo by cGMP-dependent protein kinase in smooth muscle.
- K. S. Murthy and H. Zhou (2003)
Am J Physiol Gastrointest Liver Physiol
284, G221-G230
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- Quinine Inhibits Vascular Contraction Independent of Effects on Calcium or Myosin Phosphorylation.
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J. Pharmacol. Exp. Ther.
304, 294-300
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- Functional Interplay Between Angiotensin II and Nitric Oxide: Cyclic GMP as a Key Mediator.
- C. Yan, D. Kim, T. Aizawa, and B. C. Berk (2003)
Arterioscler Thromb Vasc Biol
23, 26-36
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- cGMP-mediated signaling via cGKI{alpha} is required for the guidance and connectivity of sensory axons.
- H. Schmidt, M. Werner, P. A. Heppenstall, M. Henning, M. I. More, S. Kuhbandner, G. R. Lewin, F. Hofmann, R. Feil, and F. G. Rathjen (2002)
J. Cell Biol.
159, 489-498
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- Activation of the Mitogen Activated Protein Kinase Extracellular Signal-Regulated Kinase 1 and 2 by the Nitric Oxide-cGMP-cGMP-Dependent Protein Kinase Axis Regulates the Expression of Matrix Metalloproteinase 13 in Vascular Endothelial Cells.
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Mol. Pharmacol.
62, 927-935
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- Nitric Oxide-Induced Motility in Aortic Smooth Muscle Cells: Role of Protein Tyrosine Phosphatase SHP-2 and GTP-Binding Protein Rho.
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Circ. Res.
91, 390-397
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- cGMP-dependent Protein Kinase Ibeta Physically and Functionally Interacts with the Transcriptional Regulator TFII-I.
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277, 32003-32014
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- Regulation of Structural Plasticity by Different Channel Types in Rod and Cone Photoreceptors.
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J. Neurosci.
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- The pathophysiology of erectile dysfunction related to endothelial dysfunction and mediators of vascular function.
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Vascular Medicine
7, 213-225
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- Functional Reconstitution of Vascular Smooth Muscle Cells With cGMP-Dependent Protein Kinase I Isoforms.
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Circ. Res.
90, 1080-1086
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- Active Rho Kinase (ROK-alpha ) Associates with Insulin Receptor Substrate-1 and Inhibits Insulin Signaling in Vascular Smooth Muscle Cells.
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- A Novel Leucine Zipper Targets AKAP15 and Cyclic AMP-dependent Protein Kinase to the C Terminus of the Skeletal Muscle Ca2+ Channel and Modulates Its Function.
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- Regulation of cGMP-specific Phosphodiesterase (PDE5) Phosphorylation in Smooth Muscle Cells.
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- Gene Transfer of cGMP-Dependent Protein Kinase I Enhances the Antihypertrophic Effects of Nitric Oxide in Cardiomyocytes.
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Hypertension
39, 87-92
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- cAMP inhibits IP3-dependent Ca2+ release by preferential activation of cGMP-primed PKG.
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Am J Physiol Gastrointest Liver Physiol
281, G1238-G1245
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