SEARCH:   Advanced

Blood, 15 January 2006, Vol. 107, No. 2, pp. 575-583. Prepublished online as a Blood First Edition Paper on October 11, 2005; DOI 10.1182/blood-2004-11-4377. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-11-4377v1 107/2/575    most recent 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 Pandey, D. Articles by Siess, W. Search for Related Content PubMed PubMed Citation Articles by Pandey, D. Articles by Siess, W. Related Collections Hemostasis, Thrombosis, and Vascular Biology Cytoskeleton Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Regulation of LIM-kinase 1 and cofilin in thrombin-stimulated platelets Dharmendra Pandey, Pankaj Goyal, James R. Bamburg, and Wolfgang Siess From the Institute for Prevention of Cardiovascular Diseases, University of Munich, Munich, Germany; and the Department of Biochemistry and Molecular Biology, Colorado State University, Fort Collins. Cofilin is a regulator of actin filament dynamics. We studied whether during platelet activation Rho kinase stimulates LIM kinase (LIMK) leading to subsequent phosphorylation and inactivation of cofilin. Platelet shape change and aggregation/secretion were induced by low and high concentrations of thrombin, respectively. We found that during these platelet responses Rho kinase activation was responsible for mediating rapid Thr508 phosphorylation and activation of LIMK-1 and for the F-actin increase during shape change and, in part, during secretion. Surprisingly, during shape change cofilin phosphorylation was unaltered, and during aggregation/secretion cofilin was first rapidly dephosphorylated by an okadaic acid–insensitive phosphatase and then slowly rephosphorylated by LIMK-1. LIMK-1 phosphorylation and cofilin dephosphorylation and rephosphorylation during aggregation were independent of integrin IIb3 engagement. Cofilin phosphorylation did not regulate cofilin association with F-actin and was unrelated to the F-actin increase in thrombin-activated platelets. Our study identifies LIMK-1 as being activated by Rho kinase in thrombin-stimulated platelets. Two counteracting pathways, a cofilin phosphatase and LIMK-1, are activated during platelet aggregation/secretion regulating cofilin phosphorylation sequentially and independently of integrin IIb3 engagement. Rho kinase–mediated F-actin increase during platelet shape change and secretion involves a mechanism other than LIMK-1–mediated cofilin phosphorylation, raising the possibility of another LIMK substrate regulating platelet actin assembly. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: F. Fazal, K. M. Bijli, M. Minhajuddin, T. Rein, J. N. Finkelstein, and A. Rahman Essential Role of Cofilin-1 in Regulating Thrombin-induced RelA/p65 Nuclear Translocation and Intercellular Adhesion Molecule 1 (ICAM-1) Expression in Endothelial Cells J. Biol. Chem., July 31, 2009; 284(31): 21047 - 21056. [Abstract] [Full Text] [PDF] D. Pandey, P. Goyal, S. Dwivedi, and W. Siess Unraveling a novel Rac1-mediated signaling pathway that regulates cofilin dephosphorylation and secretion in thrombin-stimulated platelets Blood, July 9, 2009; 114(2): 415 - 424. [Abstract] [Full Text] [PDF] Y. Ding, T. Milosavljevic, and S. K. Alahari Nischarin Inhibits LIM Kinase To Regulate Cofilin Phosphorylation and Cell Invasion Mol. Cell. Biol., June 1, 2008; 28(11): 3742 - 3756. [Abstract] [Full Text] [PDF] B. T. Kile, A. D. Panopoulos, R. A. Stirzaker, D. F. Hacking, L. H. Tahtamouni, T. A. Willson, L. A. Mielke, K. J. Henley, J.-G. Zhang, I. P. Wicks, et al. Mutations in the cofilin partner Aip1/Wdr1 cause autoinflammatory disease and macrothrombocytopenia Blood, October 1, 2007; 110(7): 2371 - 2380. [Abstract] [Full Text] [PDF] C. D'hondt, S. P. Srinivas, J. Vereecke, and B. Himpens Adenosine Opposes Thrombin-Induced Inhibition of Intercellular Calcium Wave in Corneal Endothelial Cells Invest. Ophthalmol. Vis. Sci., April 1, 2007; 48(4): 1518 - 1527. [Abstract] [Full Text] [PDF]

	Copyright © 2006 by American Society of Hematology         Online ISSN: 1528-0020