Alboaggregin A activates platelets by a mechanism involving glycoprotein VI as well as glycoprotein Ib

The snake venom C-type lectin alboaggregin A (or 50-kd alboaggregin) from T rimeresurus albolabris was previously shown to be a platelet glycoprotein ( GP) Ib agonist. However, investigations of the signal transduction induced in platelets showed patterns of tyrosine phosphorylation that were differen t from those of other GPIb agonists and suggested the presence of an additi onal receptor. In this study, the binding of biotinylated alboaggregin A to platelet lysates, as well as affinity chromatography evaluations of platel et lysates on an alboaggregin A-coated column, indicated that this other re ceptor is GPVI. Additional experiments with reagents that inhibit either GP Ib or GPVI specifically supported this finding. These experiments also show ed that both GPIb and GPVI have a role in the combined signaling and that t he overall direction this takes can be influenced by inhibitors of one or t he other receptor pathway. (C) 2001 by The American Society of Hematology.