SEARCH:   Advanced

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Suzuki, Y. Articles by Nishikawa, M. Search for Related Content PubMed PubMed Citation Articles by Suzuki, Y. Articles by Nishikawa, M. Related Collections Hemostasis, Thrombosis, and Vascular Biology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, Vol. 93 No. 10 (May 15), 1999: pp. 3408-3417 Agonist-Induced Regulation of Myosin Phosphatase Activity in Human Platelets Through Activation of Rho-Kinase Yoshinori Suzuki, Masatoshi Yamamoto, Hideo Wada, Masaaki Ito, Takeshi Nakano, Yasuharu Sasaki, Shuh Narumiya, Hiroshi Shiku, and Masakatsu Nishikawa From the 2nd and the 1st Departments of Internal Medicine, Mie University School of Medicine, Tsu, Mie, Japan; Frontier 21, Life Science Research Center, Asahi Chemical Industry Co, Ltd, Fuji, Shizuoka; and the Department of Pharmacology, Kyoto University Faculty of Medicine, Kyoto, Japan. Human platelets contained about 15 times lower amounts of Rho-kinase than Ca2+/calmodulin-dependent myosin light chain (MLC) kinase. Anti-myosin-binding subunit (MBS) antibody coimmunoprecipitated Rho-kinase of human platelets, and addition of GTPS-RhoA stimulated phosphorylation of the 130-kD MBS of myosin phosphatase and consequently inactivated myosin phosphatase. Two kinds of selective Rho-kinase inhibitors, HA1077 and Y-27632, reduced both GTPS-RhoA-dependent MBS phosphorylation and inactivation of the phosphatase activity. Activation of human platelets with thrombin, a stable thromboxane A2 analog STA2, epinephrine, and serotonin resulted in an increase in MBS phosphorylation, and the agonist-induced MBS phosphorylation was prevented by pretreatment with the respective receptor antagonist. HA1077 and Y-27632 inhibited MBS phosphorylation in platelets stimulated with these agonists. These compounds also blocked agonist-induced inactivation of myosin phosphatase in intact platelets. In addition, HA1077 and Y-27632 inhibited 20-kD MLC phosphorylation at Ser19 and ATP secretion of platelets stimulated with STA2, thrombin (0.05 U/mL), and simultaneous addition of serotonin and epinephrine, whereas these compounds did not affect MLC phosphorylation or ATP secretion when platelets were stimulated with more than 0.1 U/mL thrombin. Thus, activation of Rho-kinase and the resultant phosphorylation of MBS is likely to be the common pathway for platelet activation induced by various agonists. These results also suggest that Rho-kinase-mediated MLC phosphorylation contributes to a greater extent to the platelet secretion induced by relatively weak agonists. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: L. Lian, Y. Wang, M. Flick, J. Choi, E. W. Scott, J. Degen, M. A. Lemmon, and C. S. Abrams Loss of pleckstrin defines a novel pathway for PKC-mediated exocytosis Blood, April 9, 2009; 113(15): 3577 - 3584. [Abstract] [Full Text] [PDF] C. Leon, A. Eckly, B. Hechler, B. Aleil, M. Freund, C. Ravanat, M. Jourdain, C. Nonne, J. Weber, R. Tiedt, et al. Megakaryocyte-restricted MYH9 inactivation dramatically affects hemostasis while preserving platelet aggregation and secretion Blood, November 1, 2007; 110(9): 3183 - 3191. [Abstract] [Full Text] [PDF] Y. Chang, F. Aurade, F. Larbret, Y. Zhang, J.-P. Le Couedic, L. Momeux, J. Larghero, J. Bertoglio, F. Louache, E. Cramer, et al. Proplatelet formation is regulated by the Rho/ROCK pathway Blood, May 15, 2007; 109(10): 4229 - 4236. [Abstract] [Full Text] [PDF] J.-S. Huang, L. Dong, T. Kozasa, and G. C. Le Breton Signaling through G{alpha}13 Switch Region I Is Essential for Protease-activated Receptor 1-mediated Human Platelet Shape Change, Aggregation, and Secretion J. Biol. Chem., April 6, 2007; 282(14): 10210 - 10222. [Abstract] [Full Text] [PDF] S. Offermanns Activation of Platelet Function Through G Protein-Coupled Receptors Circ. Res., December 8, 2006; 99(12): 1293 - 1304. [Abstract] [Full Text] [PDF] R. M. Vicari, B. Chaitman, D. Keefe, W. B. Smith, S. G. Chrysant, M. J. Tonkon, N. Bittar, R. J. Weiss, H. Morales-Ballejo, U. Thadani, et al. Efficacy and Safety of Fasudil in Patients With Stable Angina: A Double-Blind, Placebo-Controlled, Phase 2 Trial J. Am. Coll. Cardiol., November 15, 2005; 46(10): 1803 - 1811. [Abstract] [Full Text] [PDF] M. L. Vitale and M. E. Carbajal Involvement of Myosin II in Dopamine-induced Reorganization of the Lactotroph Cell's Actin Cytoskeleton J. Histochem. Cytochem., April 1, 2004; 52(4): 517 - 527. [Abstract] [Full Text] [PDF] G. R. John, L. Chen, M. A. Rivieccio, C. V. Melendez-Vasquez, A. Hartley, and C. F. Brosnan Interleukin-1{beta} Induces a Reactive Astroglial Phenotype via Deactivation of the Rho GTPase-Rock Axis J. Neurosci., March 17, 2004; 24(11): 2837 - 2845. [Abstract] [Full Text] [PDF] H. CEULEMANS and M. BOLLEN Functional Diversity of Protein Phosphatase-1, a Cellular Economizer and Reset Button Physiol Rev, January 1, 2004; 84(1): 1 - 39. [Abstract] [Full Text] [PDF] Z. Wang, M. C. Lanner, N. Jin, D. Swartz, L. Li, and R. A. Rhoades Hypoxia Inhibits Myosin Phosphatase in Pulmonary Arterial Smooth Muscle Cells: Role of Rho-Kinase Am. J. Respir. Cell Mol. Biol., October 1, 2003; 29(4): 465 - 471. [Abstract] [Full Text] [PDF] R. Flaumenhaft Molecular Basis of Platelet Granule Secretion Arterioscler. Thromb. Vasc. Biol., July 1, 2003; 23(7): 1152 - 1160. [Abstract] [Full Text] [PDF] E. Butt, S. Gambaryan, N. Gottfert, A. Galler, K. Marcus, and H. E. Meyer Actin Binding of Human LIM and SH3 Protein Is Regulated by cGMP- and cAMP-dependent Protein Kinase Phosphorylation on Serine 146 J. Biol. Chem., April 25, 2003; 278(18): 15601 - 15607. [Abstract] [Full Text] [PDF] S. M. Schoenwaelder, S. C. Hughan, K. Boniface, S. Fernando, M. Holdsworth, P. E. Thompson, H. H. Salem, and S. P. Jackson RhoA Sustains Integrin alpha IIbbeta 3 Adhesion Contacts under High Shear J. Biol. Chem., April 19, 2002; 277(17): 14738 - 14746. [Abstract] [Full Text] [PDF] Y. Watanabe, M. Ito, Y. Kataoka, H. Wada, M. Koyama, J. Feng, H. Shiku, and M. Nishikawa Protein kinase C-catalyzed phosphorylation of an inhibitory phosphoprotein of myosin phosphatase is involved in human platelet secretion Blood, June 15, 2001; 97(12): 3798 - 3805. [Abstract] [Full Text] [PDF] G. P. van Nieuw Amerongen and V. W.M. van Hinsbergh Cytoskeletal Effects of Rho-Like Small Guanine Nucleotide-Binding Proteins in the Vascular System Arterioscler. Thromb. Vasc. Biol., March 1, 2001; 21(3): 300 - 311. [Abstract] [Full Text] [PDF] G. P. v. N. Amerongen, S. v. Delft, M. A. Vermeer, J. G. Collard, and V. W. M. van Hinsbergh Activation of RhoA by Thrombin in Endothelial Hyperpermeability : Role of Rho Kinase and Protein Tyrosine Kinases Circ. Res., August 18, 2000; 87(4): 335 - 340. [Abstract] [Full Text] [PDF] T. Ishizaki, M. Uehata, I. Tamechika, J. Keel, K. Nonomura, M. Maekawa, and S. Narumiya Pharmacological Properties of Y-27632, a Specific Inhibitor of Rho-Associated Kinases Mol. Pharmacol., May 1, 2000; 57(5): 976 - 983. [Abstract] [Full Text] A. P Somlyo and A. V Somlyo Signal transduction by G-proteins, Rho-kinase and protein phosphatase to smooth muscle and non-muscle myosin II J. Physiol., January 15, 2000; 522(2): 177 - 185. [Abstract] [Full Text] [PDF] J. Feng, M. Ito, K. Ichikawa, N. Isaka, M. Nishikawa, D. J. Hartshorne, and T. Nakano Inhibitory Phosphorylation Site for Rho-associated Kinase on Smooth Muscle Myosin Phosphatase J. Biol. Chem., December 24, 1999; 274(52): 37385 - 37390. [Abstract] [Full Text] [PDF]

	Copyright © 1999 by American Society of Hematology         Online ISSN: 1528-0020