SEARCH:   Advanced

Blood, 15 January 2008, Vol. 111, No. 2, pp. 651-657. Prepublished online as a Blood First Edition Paper on September 27, 2007; DOI 10.1182/blood-2007-05-093021. This Article Full Text (PDF) All Versions of this Article: blood-2007-05-093021v1 111/2/651    most recent Alert me when this article is cited Alert me if a correction is posted 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 Shim, K. Articles by Sadler, J E. Search for Related Content PubMed PubMed Citation Articles by Shim, K. Articles by Sadler, J E. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted May 30, 2007 Accepted September 25, 2007 Platelet-VWF complexes are preferred substrates of ADAMTS13 under fluid shear stress Kyuhwan Shim, Patricia J. Anderson, Elodee A. Tuley, Erin Wiswall, and J Evan Sadler* Dept of Med, Dept of Biochemistry & Molecular Biophysics, & Howard Hughes Medical Institute, Washington University School of Medicine, St. Louis, MO Wyeth Biotech, Andover, MA * Corresponding author; email: esadler{at}im.wustl.edu. Endothelial cells secrete prothrombotic ultralarge von Willebrand factor (VWF) multimers, and the metalloprotease ADAMTS13 cleaves them into smaller, less dangerous multimers. This reaction is stimulated by tensile force applied to the VWF substrate, which may occur on cell surfaces or in the circulating blood. The cleavage of soluble VWF by ADAMTS13 was accelerated dramatically by a combination of platelets and fluid shear stress applied in a cone-plate viscometer. Platelet-dependent cleavage of VWF was blocked by an anti GPIb monoclonal antibody or by a recombinant soluble fragment of GPIb that prevents platelet-VWF binding. Multimeric gel analysis showed that shear and platelet-dependent cleavage consumed large VWF multimers. Therefore, ADAMTS13 preferentially acts on platelet-VWF complexes under fluid shear stress. This reaction is likely to account for a majority of VWF proteolysis after secretion and to determine the steady state size distribution of circulating VWF multimers in vivo. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Platelet-VWF complexes get the chop Michael C. Berndt and Robert K. Andrews Blood 2008 111: 475. [Full Text] [PDF] This article has been cited by other articles: A. N. Vomund and E. M. Majerus ADAMTS13 Bound to Endothelial Cells Exhibits Enhanced Cleavage of von Willebrand Factor J. Biol. Chem., November 6, 2009; 284(45): 30925 - 30932. [Abstract] [Full Text] [PDF] S. Zanardelli, A. C. K. Chion, E. Groot, P. J. Lenting, T. A. J. McKinnon, M. A. Laffan, M. Tseng, and D. A. Lane A novel binding site for ADAMTS13 constitutively exposed on the surface of globular VWF Blood, September 24, 2009; 114(13): 2819 - 2828. [Abstract] [Full Text] [PDF] X. Zhang, K. Halvorsen, C.-Z. Zhang, W. P. Wong, and T. A. Springer Mechanoenzymatic Cleavage of the Ultralarge Vascular Protein von Willebrand Factor Science, June 5, 2009; 324(5932): 1330 - 1334. [Abstract] [Full Text] [PDF] F. Banno, A. K. Chauhan, K. Kokame, J. Yang, S. Miyata, D. D. Wagner, and T. Miyata The distal carboxyl-terminal domains of ADAMTS13 are required for regulation of in vivo thrombus formation Blood, May 21, 2009; 113(21): 5323 - 5329. [Abstract] [Full Text] [PDF] M. W. Massyn and S. A. Khan Heyde syndrome: a common diagnosis in older patients with severe aortic stenosis Age Ageing, May 1, 2009; 38(3): 267 - 270. [Abstract] [Full Text] [PDF] P. Nurden The VWD2B saga continues to Montreal Blood, April 2, 2009; 113(14): 3134 - 3135. [Full Text] [PDF] D. F. Cutler Fishing for platelets Blood, February 12, 2009; 113(7): 1397 - 1398. [Full Text] [PDF] J. Huang, R. Roth, J. E. Heuser, and J. E. Sadler Integrin {alpha}v{beta}3 on human endothelial cells binds von Willebrand factor strings under fluid shear stress Blood, February 12, 2009; 113(7): 1589 - 1597. [Abstract] [Full Text] [PDF] C. G. Skipwith, W. Cao, and X. L. Zheng Factor VIII and Platelets Cooperatively Accelerate Proteolytic Cleavage of Von Willebrand Factor by ADAMTS13 Under Shear Stress Blood (ASH Annual Meeting Abstracts), November 16, 2008; 112(11): 590 - 590. [Abstract] W. Gao, P. J. Anderson, and J. E. Sadler Extensive contacts between ADAMTS13 exosites and von Willebrand factor domain A2 contribute to substrate specificity Blood, September 1, 2008; 112(5): 1713 - 1719. [Abstract] [Full Text] [PDF]

	Copyright © 2007 by American Society of Hematology         Online ISSN: 1528-0020