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Science 19 November 1999:
Vol. 286. no. 5444, pp. 1583 - 1587
DOI: 10.1126/science.286.5444.1583

Reports

Regulation of Myosin Phosphatase by a Specific Interaction with cGMP- Dependent Protein Kinase Ialpha

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 Ialpha (cGKIalpha ) mediates physiologic relaxation of vascular smooth muscle in response to nitric oxide and cGMP. It is shown here that cGKIalpha 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 cGKIalpha -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


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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
   Abstract »    Full Text »    PDF »
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
   Abstract »    Full Text »    PDF »
Quinine Inhibits Vascular Contraction Independent of Effects on Calcium or Myosin Phosphorylation.
B. Adegunloye, E. Lamarre, and R. S. Moreland (2003)
J. Pharmacol. Exp. Ther. 304, 294-300
   Abstract »    Full Text »    PDF »
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
   Abstract »    Full Text »    PDF »
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
   Abstract »    Full Text »    PDF »
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.
C. Zaragoza, E. Soria, E. Lopez, D. Browning, M. Balbin, C. Lopez-Otin, and S. Lamas (2002)
Mol. Pharmacol. 62, 927-935
   Abstract »    Full Text »    PDF »
Nitric Oxide-Induced Motility in Aortic Smooth Muscle Cells: Role of Protein Tyrosine Phosphatase SHP-2 and GTP-Binding Protein Rho.
Y. Chang, B. Ceacareanu, M. Dixit, N. Sreejayan, and A. Hassid (2002)
Circ. Res. 91, 390-397
   Abstract »    Full Text »    PDF »
cGMP-dependent Protein Kinase Ibeta Physically and Functionally Interacts with the Transcriptional Regulator TFII-I.
D. E. Casteel, S. Zhuang, T. Gudi, J. Tang, M. Vuica, S. Desiderio, and R. B. Pilz (2002)
J. Biol. Chem. 277, 32003-32014
   Abstract »    Full Text »    PDF »
Regulation of Structural Plasticity by Different Channel Types in Rod and Cone Photoreceptors.
N. Zhang and E. Townes-Anderson (2002)
J. Neurosci. 22, 7065-7079
   Abstract »    Full Text »    PDF »
The pathophysiology of erectile dysfunction related to endothelial dysfunction and mediators of vascular function.
R. Maas, E. Schwedhelm, J. Albsmeier, and R. H Boger (2002)
Vascular Medicine 7, 213-225
   Abstract »    PDF »
Functional Reconstitution of Vascular Smooth Muscle Cells With cGMP-Dependent Protein Kinase I Isoforms.
R. Feil, N. Gappa, M. Rutz, J. Schlossmann, C. R. Rose, A. Konnerth, S. Brummer, S. Kuhbandner, and F. Hofmann (2002)
Circ. Res. 90, 1080-1086
   Abstract »    Full Text »    PDF »
Active Rho Kinase (ROK-alpha ) Associates with Insulin Receptor Substrate-1 and Inhibits Insulin Signaling in Vascular Smooth Muscle Cells.
N. Begum, O. A. Sandu, M. Ito, S. M. Lohmann, and A. Smolenski (2002)
J. Biol. Chem. 277, 6214-6222
   Abstract »    Full Text »    PDF »
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.
J. T. Hulme, M. Ahn, S. D. Hauschka, T. Scheuer, and W. A. Catterall (2002)
J. Biol. Chem. 277, 4079-4087
   Abstract »    Full Text »    PDF »
Regulation of cGMP-specific Phosphodiesterase (PDE5) Phosphorylation in Smooth Muscle Cells.
S. D. Rybalkin, I. G. Rybalkina, R. Feil, F. Hofmann, and J. A. Beavo (2002)
J. Biol. Chem. 277, 3310-3317
   Abstract »    Full Text »    PDF »
Gene Transfer of cGMP-Dependent Protein Kinase I Enhances the Antihypertrophic Effects of Nitric Oxide in Cardiomyocytes.
K. C. Wollert, B. Fiedler, S. Gambaryan, A. Smolenski, J. Heineke, E. Butt, C. Trautwein, S. M. Lohmann, and H. Drexler (2002)
Hypertension 39, 87-92
   Abstract »    Full Text »    PDF »
cAMP inhibits IP3-dependent Ca2+ release by preferential activation of cGMP-primed PKG.
K. S. Murthy (2001)
Am J Physiol Gastrointest Liver Physiol 281, G1238-G1245
   Abstract »    Full Text »    PDF »



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