Activation of protein-tyrosine kinase pathways in human platelets stimulated with the A1 domain of von Willebrand factor.

Abstract	The binding of multimeric von Willebrand Factor (vWF) to its specific receptor on platelets, glycoprotein (GP)Ib, is a critical event, allowing platelet activation and subsequent thrombus formation in the vessels. In this study, the effects of the monomeric A1 domain, which contains the GPIb-binding site of the vWF molecule, on platelet activation were examined. The binding of the A1 domain to GPIb resulted in Syk activation and association with Src, as is the case with intact vWF. However, the A1 domain, in contrast to vWF, did not induce platelet cytoskeletal association of tyrosine kinases, Src and Lyn. When platelet functional responses, such as aggregation and intracellular Ca2+ mobilization, were monitored, the A1 domain failed to induce the responses by itself and blocked the responses induced by the multimeric vWF molecule. These results suggested that the A1 domain triggers at least some of tyrosine kinase-related signals via GPIb and may be a partial agonist as well as a competitive antagonist for the vWF-GPIb interaction.
Authors	K Satoh, N Asazuma, Y Yatomi, Y Fujimura, S Miura, K Titani, Y Ozaki
Journal	Platelets (Platelets) Vol. 11 Issue 3 Pg. 171-6 (May 2000) ISSN: 0953-7104 [Print] England
PMID	10938894 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Crotalid Venoms Enzyme Precursors Hemagglutinins Intracellular Signaling Peptides and Proteins von Willebrand Factor botrocetin Protein-Tyrosine Kinases SYK protein, human Syk Kinase src-Family Kinases
Topics	Blood Platelets (drug effects, enzymology, metabolism) Blotting, Western Calcium Signaling (drug effects) Crotalid Venoms (pharmacology) Cytoskeleton (metabolism) Enzyme Activation Enzyme Precursors (drug effects, metabolism) Hemagglutinins (pharmacology) Humans Intracellular Signaling Peptides and Proteins Platelet Aggregation (drug effects) Protein Binding Protein Structure, Tertiary Protein-Tyrosine Kinases (drug effects, metabolism) Signal Transduction (drug effects) Syk Kinase src-Family Kinases von Willebrand Factor (chemistry, metabolism, pharmacology)

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