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Related Collections Hemostasis, Thrombosis, and Vascular Biology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, Vol. 94 No. 5 (September 1), 1999: pp. 1648-1656 Glycoprotein Ib-V-IX, a Receptor for von Willebrand Factor, Couples Physically and Functionally to the Fc Receptor -Chain, Fyn, and Lyn to Activate Human Platelets Shahrokh Falati, Christine E. Edmead, and Alastair W. Poole From the Department of Pharmacology, University of Bristol, School of Medical Sciences, Bristol, UK. The adhesion molecule von Willebrand factor (vWF) activates platelets upon binding 2 surface receptors, glycoprotein (GP) Ib-V-IX and integrin IIb3. We have used 2 approaches to selectively activate GP Ib using either the snake venom lectin alboaggregin-A or mutant recombinant forms of vWF (A1-vWF and RGGS-vWF) with selective binding properties to its 2 receptors. We show that activation of GP Ib induces platelet aggregation, secretion of 5-hydroxy tryptamine (5-HT), and an increase in cytosolic calcium. Syk becomes tyrosine phosphorylated and activated downstream of GP Ib, and associates with several tyrosine-phosphorylated proteins including the Fc receptor -chain through interaction with Syk SH2 domains. GP Ib physically associates with the -chain in GST-Syk-SH2 precipitates from platelets stimulated through GP Ib, and 2 Src family kinases, Lyn and Fyn, also associate with this signaling complex. In addition, GP Ib stimulation couples to tyrosine phosphorylation of phospholipase C2. The Src family-specific inhibitor PP1 dose-dependently inhibits phosphorylation of Syk, its association with tyrosine-phosphorylated -chain, phosphorylation of PLC2, platelet aggregation, and 5-HT release. The results indicate that, upon activation, GP Ib is physically associated with FcR -chain and members of the Src family kinases, leading to phosphorylation of the -chain, recruitment, and activation of Syk. Phosphorylation of PLC2 also lies downstream of Src kinase activation and may critically couple early signaling events to functional platelet responses. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: F. Mancini, S. Rigacci, A. Berti, C. Balduini, and M. Torti The low-molecular-weight phosphotyrosine phosphatase is a negative regulator of Fc{gamma}RIIA-mediated cell activation Blood, September 15, 2007; 110(6): 1871 - 1878. [Abstract] [Full Text] [PDF] F. A. Lee, M. van Lier, I. A. M. Relou, L. Foley, J.-W. N. Akkerman, H. F. G. Heijnen, and R. W. Farndale Lipid Rafts Facilitate the Interaction of PECAM-1 with the Glycoprotein VI-FcR {gamma}-Chain Complex in Human Platelets J. Biol. 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