Published online before print February 14, 2002, doi: 10.1161/01.RES.0000012822.23273.EC
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
© 2002 American Heart Association, Inc.
Molecular Medicine |
Differential Association and Localization of Myosin Phosphatase Subunits During Agonist-Induced Signal Transduction in Smooth Muscle
From the Boston Biomedical Research Institute (H.-M.S., H.-D.J., C.G., T.C.T., K.G.M.), Watertown, Mass; the Department of Physiology (H.-M.S.), Dongguk University College of Oriental Medicine, Kyongju, Kyongbuk, Korea; the Department of Chemistry (T.C.T.), Tufts University School of Medicine, Boston, Mass; the Department of Neurology (T.C.T), and Department of Medicine, Beth Israel Deaconess Medical Center (K.G.M.), Harvard Medical School, Boston, Mass; the Muscle Biology Group (D.J.H.), University of Arizona, Tucson, Ariz; and the First Department of Internal Medicine (M.I.), Mie University School of Medicine, Tsu, Mie, Japan.
Correspondence to Kathleen G. Morgan, PhD, Boston Biomedical Research Institute, 64 Grove St, Watertown, MA 02472. E-mail morgan{at}BBRI.org
It has been known for some time that agonist-induced contractions of vascular smooth muscle are often associated with a sensitization of the contractile apparatus to intracellular Ca2+. One mechanism that has been suggested to explain Ca2+ sensitization is inhibition of myosin phosphatase activity. In the present study, we tested the hypothesis that differential localization of the phosphatase might be associated with its inhibition. Quantitative confocal microscopy of freshly dissociated, fully contractile smooth muscle cells was used in parallel with measurements of myosin light chain and myosin phosphatase phosphorylation. The results indicate that, in the smooth muscle cells, the catalytic and targeting subunits of the phosphatase are dissociated from each other in an agonist-specific manner and that the dissociation is accompanied by a slower rate of myosin phosphorylation. Targeting of myosin phosphatase to the cell membrane precedes the dissociation of subunits and is associated with phosphorylation of the targeting subunit at a Rho-associated kinase (ROK) phosphorylation site. The phosphorylation and membrane translocation of the targeting subunit are inhibited by a ROK inhibitor. This dissociation of subunits may provide a mechanism for the decreased phosphatase activity of phosphorylated myosin phosphatase.
Key Words: myosin phosphatase • smooth muscle • Rho-associated kinase • contractility • myosin phosphorylation
This article has been cited by other articles:
 |
|
 |
|
  S. Puetz, L. T. Lubomirov, and G. Pfitzer Regulation of Smooth Muscle Contraction by Small GTPases Physiology, December 1, 2009; 24(6): 342 - 356. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Wang, D. M. Kendig, E. M. Smolock, and R. S. Moreland Carbachol-induced rabbit bladder smooth muscle contraction: roles of protein kinase C and Rho kinase Am J Physiol Renal Physiol, December 1, 2009; 297(6): F1534 - F1542. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Khromov, N. Choudhury, A. S. Stevenson, A. V. Somlyo, and M. Eto Phosphorylation-dependent Autoinhibition of Myosin Light Chain Phosphatase Accounts for Ca2+ Sensitization Force of Smooth Muscle Contraction J. Biol. Chem., August 7, 2009; 284(32): 21569 - 21579. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. P. Johnson, A. F. El-Yazbi, K. Takeya, E. J. Walsh, M. P. Walsh, and W. C. Cole Ca2+ sensitization via phosphorylation of myosin phosphatase targeting subunit at threonine-855 by Rho kinase contributes to the arterial myogenic response J. Physiol., June 1, 2009; 587(11): 2537 - 2553. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. L. Neppl, L. T. Lubomirov, K. Momotani, G. Pfitzer, M. Eto, and A. V. Somlyo Thromboxane A2-induced Bi-directional Regulation of Cerebral Arterial Tone J. Biol. Chem., March 6, 2009; 284(10): 6348 - 6360. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Mizuno, E. Isotani, J. Huang, H. Ding, J. T. Stull, and K. E. Kamm Myosin light chain kinase activation and calcium sensitization in smooth muscle in vivo Am J Physiol Cell Physiol, August 1, 2008; 295(2): C358 - C364. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Li, K. Kozlowski, B. Wegner, T. Rashid, T. Yeung, C. Holmes, and B. J. Ballermann Phosphorylation of TIMAP by Glycogen Synthase Kinase-3beta Activates Its Associated Protein Phosphatase 1 J. Biol. Chem., August 31, 2007; 282(35): 25960 - 25969. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F.V. Hartel, C.W. Rodewald, M. Aslam, D. Gunduz, L. Hafer, J. Neumann, H.M. Piper, and T. Noll Extracellular ATP induces assembly and activation of the myosin light chain phosphatase complex in endothelial cells Cardiovasc Res, June 1, 2007; 74(3): 487 - 496. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Hagerty, D. H. Weitzel, J. Chambers, C. N. Fortner, M. H. Brush, D. Loiselle, H. Hosoya, and T. A. J. Haystead ROCK1 Phosphorylates and Activates Zipper-interacting Protein Kinase J. Biol. Chem., February 16, 2007; 282(7): 4884 - 4893. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. K. Mehta and K. K. Griendling Angiotensin II cell signaling: physiological and pathological effects in the cardiovascular system Am J Physiol Cell Physiol, January 1, 2007; 292(1): C82 - C97. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Yong, I. Tan, L. Lim, and T. Leung Phosphorylation of Myosin Phosphatase Targeting Subunit 3 (MYPT3) and Regulation of Protein Phosphatase 1 by Protein Kinase A J. Biol. Chem., October 20, 2006; 281(42): 31202 - 31211. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. B. Patil and K. N. Bitar RhoA- and PKC-{alpha}-mediated phosphorylation of MYPT and its association with HSP27 in colonic smooth muscle cells. Am J Physiol Gastrointest Liver Physiol, January 1, 2006; 290(1): G83 - G95. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. K. Surks, N. Riddick, and K.-i. Ohtani M-RIP Targets Myosin Phosphatase to Stress Fibers to Regulate Myosin Light Chain Phosphorylation in Vascular Smooth Muscle Cells J. Biol. Chem., December 30, 2005; 280(52): 42543 - 42551. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. H. P. Hilgers and R. C. Webb Molecular Aspects of Arterial Smooth Muscle Contraction: Focus on Rho Exp Biol Med, December 1, 2005; 230(11): 829 - 835. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Sakai, T. Hirano, Y. Chiba, and M. Misawa Acetylcholine-induced phosphorylation and membrane translocation of CPI-17 in bronchial smooth muscle of rats Am J Physiol Lung Cell Mol Physiol, December 1, 2005; 289(6): L925 - L930. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Sakai, Y. Chiba, T. Hirano, and M. Misawa Possible Involvement of CPI-17 in Augmented Bronchial Smooth Muscle Contraction in Antigen-Induced Airway Hyper-Responsive Rats Mol. Pharmacol., July 1, 2005; 68(1): 145 - 151. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Watanabe, F. M. Faraci, and D. D. Heistad Activation of Rho-associated kinase during augmented contraction of the basilar artery to serotonin after subarachnoid hemorrhage Am J Physiol Heart Circ Physiol, June 1, 2005; 288(6): H2653 - H2658. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Xiao, L. D. Longo, and L. Zhang {alpha}1-Adrenoceptor-mediated phosphorylation of MYPT-1 and CPI-17 in the uterine artery: role of ERK/PKC Am J Physiol Heart Circ Physiol, June 1, 2005; 288(6): H2828 - H2835. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. L. Jernigan, B. R. Walker, and T. C. Resta Chronic hypoxia augments protein kinase G-mediated Ca2+ desensitization in pulmonary vascular smooth muscle through inhibition of RhoA/Rho kinase signaling Am J Physiol Lung Cell Mol Physiol, December 1, 2004; 287(6): L1220 - L1229. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Zaugg and M. C. Schaub Cellular mechanisms in sympatho-modulation of the heart Br. J. Anaesth., July 1, 2004; 93(1): 34 - 52. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. L. O. Buxton Regulation of Uterine Function: a Biochemical Conundrum in the Regulation of Smooth Muscle Relaxation Mol. Pharmacol., May 1, 2004; 65(5): 1051 - 1059. [Abstract] [Full Text]
|
|
|
|
 |
|
 K. Hirano, D. N. Derkach, M. Hirano, J. Nishimura, S. Takahashi, and H. Kanaide Transduction of the N-Terminal Fragments of MYPT1 Enhances Myofilament Ca2+ Sensitivity in an Intact Coronary Artery Arterioscler Thromb Vasc Biol, March 1, 2004; 24(3): 464 - 469. [Abstract] [Full Text]
|
|
|
|
 |
|
 A. J. Piekny, J.-L. F. Johnson, G. D. Cham, and P. E. Mains The Caenorhabditis elegans nonmuscle myosin genes nmy-1 and nmy-2 function as redundant components of the let-502/Rho-binding kinase and mel-11/myosin phosphatase pathway during embryonic morphogenesis Development, December 1, 2003; 130(23): 5695 - 5704. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Durier, C. Fassot, S. Laurent, P. Boutouyrie, J.-P. Couetil, E. Fine, P. Lacolley, V. J. Dzau, and R. E. Pratt Physiological Genomics of Human Arteries: Quantitative Relationship Between Gene Expression and Arterial Stiffness Circulation, October 14, 2003; 108(15): 1845 - 1851. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. P. SOMLYO and A. V. SOMLYO Ca2+ Sensitivity of Smooth Muscle and Nonmuscle Myosin II: Modulated by G Proteins, Kinases, and Myosin Phosphatase Physiol Rev, October 1, 2003; 83(4): 1325 - 1358. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. V. Brozovich Rho Signaling: Agonist Stimulation and Depolarization Come Together Circ. Res., September 19, 2003; 93(6): 481 - 483. [Full Text] [PDF]
|
|
|
|
|
|
S.-S. Bolz, L. Vogel, D. Sollinger, R. Derwand, C. de Wit, G. Loirand, and U. Pohl 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 Circulation, June 24, 2003; 107(24): 3081 - 3087. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Teoh, M. Zacour, A. D. Wener, L. Gunaratnam, and M. E. Ward Increased myofibrillar protein phosphatase-1 activity impairs rat aortic smooth muscle activation after hypoxia Am J Physiol Heart Circ Physiol, April 1, 2003; 284(4): H1182 - H1189. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Ito, E. Shimomura, T. Iwanaga, M. Shiraishi, K. Shindo, J. Nakamura, H. Nagumo, M. Seto, Y. Sasaki, and Y. Takuwa Essential role of rho kinase in the ca2+ sensitization of prostaglandin F2{alpha}-induced contraction of rabbit aortae J. Physiol., February 1, 2003; 546(3): 823 - 836. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Guo, W. Su, Z. Ma, G. M. Smith, and M. C. Gong Ca2+-independent Phospholipase A2 Is Required for Agonist-induced Ca2+ Sensitization of Contraction in Vascular Smooth Muscle J. Biol. Chem., January 10, 2003; 278(3): 1856 - 1863. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. V. Brozovich Myosin Light Chain Phosphatase: It Gets Around Circ. Res., March 22, 2002; 90(5): 500 - 502. [Full Text] [PDF]
|
|