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 Trimeresurus 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 different from those of other GPIb agonists and suggested the presence of an additional receptor. In this study, the binding of biotinylated alboaggregin A to platelet lysates, as well as affinity chromatography evaluations of platelet lysates on an alboaggregin A-coated column, indicated that this other receptor is GPVI. Additional experiments with reagents that inhibit either GPIb or GPVI specifically supported this finding. These experiments also showed that both GPIb and GPVI have a role in the combined signaling and that the overall direction this takes can be influenced by inhibitors of one or the other receptor pathway.
Dörmann
D
D
Theodor Kocher Institute, University of Berne, Berne, Switzerland.
Clemetson
J M
JM
Navdaev
A
A
Kehrel
B E
BE
Clemetson
K J
KJ
D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D017304:Annexin A5 / Q000378:metabolism; D019921:Biotinylation; D001777:Blood Coagulation / Q000187:drug effects; D001792:Blood Platelets / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D002846:Chromatography, Affinity; D003435:Crotalid Venoms / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*; D003594:Cytoplasmic Granules / Q000378:metabolism; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000494:pharmacology; D007527:Isoenzymes / Q000378:metabolism; D037181:Lectins, C-Type; D008565:Membrane Proteins; D051966:Phospholipase C gamma; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D015539:Platelet Activation / Q000187:drug effects* / Q000502:physiology; D010973:Platelet Adhesiveness / Q000187:drug effects; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000819:agonists*; D010980:Platelet Membrane Glycoproteins / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D011485:Protein Binding; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D011506:Proteins / Q000494:pharmacology; D017452:Receptors, IgG / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D010738:Type C Phospholipases / Q000378:metabolism; D014757:Viper Venoms / Q000737:chemistry
D048868:Adaptor Proteins, Signal Transducing; D017304:Annexin A5; D002352:Carrier Proteins; D003435:Crotalid Venoms; D007140:Immunoglobulin Fab Fragments; D007527:Isoenzymes; C110810:LAT protein, human; D037181:Lectins, C-Type; D008565:Membrane Proteins; D010750:Phosphoproteins; D019038:Platelet Glycoprotein GPIb-IX Complex; D010980:Platelet Membrane Glycoproteins; D011506:Proteins; D017452:Receptors, IgG; D014757:Viper Venoms; C112003:alboaggregin A; C098341:platelet membrane glycoprotein VI; C080995:echicetin; C028890:convulxin; D010738:Type C Phospholipases; D051966:Phospholipase C gamma