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Prepublished online as a Blood First Edition Paper on August 29, 2002; DOI 10.1182/blood-2002-03-0806. This Article Full Text Full Text (PDF) All Versions of this Article: 2002-03-0806v1 101/9/3469    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 Wu, Y. Articles by Ozaki, Y. Search for Related Content PubMed PubMed Citation Articles by Wu, Y. Articles by Ozaki, Y. Related Collections Hematopoiesis and Stem Cells Cell Adhesion and Motility Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 May 2003, Vol. 101, No. 9, pp. 3469-3476 HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Interaction between von Willebrand factor and glycoprotein Ib activates Src kinase in human platelets: role of phosphoinositide 3-kinase Yi Wu, Naoki Asazuma, Kaneo Satoh, Yutaka Yatomi, Toshiro Takafuta, Michael C. Berndt, and Yukio Ozaki From the Department of Clinical and Laboratory Medicine, Faculty of Medicine, University of Yamanashi, Tamaho, Nakakoma, Yamanashi, Japan, and the Department of Biochemistry and Molecular Biology, Monash University, Victoria, Australia. The binding of von Willebrand factor (VWF) to glycoprotein (GP) Ib-IX-V stimulates transmembrane signaling events that lead to platelet adhesion and aggregation. Recent studies have implied that activation of Src family kinases is involved in GPIb-mediated platelet activation, although the related signal transduction pathway remains poorly defined. This study presents evidence for an important role of Src and GPIb association. In platelet lysates containing Complete, a broad-spectrum protease inhibitor mixture, Src and Lyn dynamically associated with GPIb on VWF-botrocetin stimulation. Cytochalasin D, which inhibits translocation of Src kinases to the cytoskeleton, further increased Src and GPIb association. Similar results were obtained with botrocetin and monomeric A1 domain, instead of intact VWF, with induction of both Src activation and association between GPIb and Src. These findings suggest that ligand binding of GPIb, without receptor clustering, is sufficient to activate Src. Immunoprecipitation studies demonstrated that Src, phosphoinositide 3- kinase (PI 3-kinase), and GPIb form a complex in GPIb-stimulated platelets. When the p85 subunit of PI 3-kinase was immunodepleted, association of Src with GPIb was abrogated. However, wortmannin, a specific PI 3-kinase inhibitor, failed to block complex formation between Src and GPIb. The Src-SH3 domain as a glutathione S-transferase (GST)-fusion protein coprecipitated the p85 subunit of PI 3-kinase and GPIb. These findings taken together suggest that the p85 subunit of PI 3-kinase mediates GPIb-related activation signals and activates Src independently of the enzymatic activity of PI 3- kinase. © 2003 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: Y. Li, J. Lu, and E. V. Prochownik Modularity of the Oncoprotein-like Properties of Platelet Glycoprotein Ib{alpha} J. Biol. Chem., January 16, 2009; 284(3): 1410 - 1418. [Abstract] [Full Text] [PDF] B. Boylan, C. Gao, V. Rathore, J. C. Gill, D. K. Newman, and P. J. 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