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Blood, 15 August 2008, Vol. 112, No. 4, pp. 1139-1146. Prepublished online as a Blood First Edition Paper on June 11, 2008; DOI 10.1182/blood-2008-02-140970. This Article Full Text (PDF) All Versions of this Article: blood-2008-02-140970v1 112/4/1139    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 Yin, H. Articles by Du, X. Search for Related Content PubMed PubMed Citation Articles by Yin, H. Articles by Du, X. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted February 22, 2008 Accepted June 2, 2008 Src family tyrosine kinase Lyn mediates VWF/GPIb-IX-induced platelet activation via the cGMP signaling pathway Hong Yin, Junling Liu, Zhenyu Li, Michael C Berndt, Clifford A Lowell, and Xiaoping Du* Department of Pharmacology, University of Illinois at Chicago, Chicago, IL, United States Department of Immunology, Monash University, Melbourne, VIC, Australia Department of Laboratory Medicine, University of California, San Francisco, San Francisco, CA, United States * Corresponding author; email: xdu{at}uic.edu. The platelet receptor for von Willebrand factor (VWF), glycoprotein (GP) Ib-IX, mediates initial platelet adhesion and transmits signals leading to platelet activation. Src family tyrosine kinases (SFK) play an important role in VWF-induced GPIb-IX signaling. However, the SFK-dependent downstream signaling pathway is unclear, but is thought to involve thromboxane A2 (TXA2) synthesis. Here we show that while platelets deficient in SFK members, Lyn or Fyn, were defective in the TXA2-dependent second wave of platelet aggregation induced by botrocetin/VWF, only Lyn-knockout platelets were also defective in stable platelet adhesion to VWF under shear stress that is independent of the TXA2 pathway. Lyn-knockout platelets also spread poorly on VWF, but spread normally on fibrinogen, indicating an important role for Lyn in VWF-mediated GPIb signaling but not in integrin outside-in signaling. Importantly, Lyn knockout abrogated VWF-induced cGMP elevation. Addition of low concentrations of 8-Bromo-cGMP, however, corrected the defective stable adhesion of Lyn-knockout platelets or PP2-treated platelets on VWF. These results demonstrate an important role for Lyn in VWF/GPIb-IX-induced integrin activation mediated via the cGMP signaling pathway independently of TXA2 synthesis and also indicate that Lyn is critically important in GPIb-IX-mediated activation of the cGMP pathway. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M.-P. Gratacap, V. Martin, M.-C. Valera, S. Allart, C. Garcia, P. Sie, C. Recher, and B. Payrastre The new tyrosine-kinase inhibitor and anticancer drug dasatinib reversibly affects platelet activation in vitro and in vivo Blood, August 27, 2009; 114(9): 1884 - 1892. [Abstract] [Full Text] [PDF]

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