Activation of protein-tyrosine kinase pathways in human platelets stimulated with the A1 domain of von Willebrand factor.
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.
Department of Clinical and Laboratory Medicine, Yamanashi Medical University, Japan.
K
K
Satoh
N
N
Asazuma
Y
Y
Yatomi
Y
Y
Fujimura
S
S
Miura
K
K
Titani
Y
Y
Ozaki
D001792:Blood Platelets / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D015153:Blotting, Western; D020013:Calcium Signaling / Q000187:drug effects; D003435:Crotalid Venoms / Q000494:pharmacology; D003599:Cytoskeleton / Q000378:metabolism; D004789:Enzyme Activation; D004792:Enzyme Precursors / Q000187:drug effects / Q000378:metabolism; D006388:Hemagglutinins / Q000494:pharmacology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D010974:Platelet Aggregation / Q000187:drug effects; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011505:Protein-Tyrosine Kinases / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D000072377:Syk Kinase; D019061:src-Family Kinases; D014841:von Willebrand Factor / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*
D003435:Crotalid Venoms; D004792:Enzyme Precursors; D006388:Hemagglutinins; D047908:Intracellular Signaling Peptides and Proteins; D014841:von Willebrand Factor; C030961:botrocetin; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase; D019061:src-Family Kinases