title: Echicetin, a GPIb-binding snake C-type lectin from Echis carinatus, also contains a binding site for IgMkappa responsible for platelet agglutination in plasma and inducing signal transduction.
abstract: Echicetin, a heterodimeric snake C-type lectin from Echis carinatus, is known to bind specifically to platelet glycoprotein (GP)Ib. We now show that, in addition, it agglutinates platelets in plasma and induces platelet signal transduction. The agglutination is caused by binding to a specific protein in plasma. The protein was isolated from plasma and shown to cause platelet agglutination when added to washed platelets in the presence of echicetin. It was identified as immunoglobulin Mkappa (IgMkappa) by peptide sequencing and dot blotting with specific heavy and light chain anti-immunoglobulin reagents. Platelet agglutination by clustering echicetin with IgMkappa induced P-selectin expression and activation of GPIIb/IIIa as well as tyrosine phosphorylation of several signal transduction molecules, including p53/56(LYN), p64, p72(SYK), p70 to p90, and p120. However, neither ethylenediaminetetraacetic acid nor specific inhibition of GPIIb/IIIa affected platelet agglutination or activation by echicetin. Platelet agglutination and induction of signal transduction could also be produced by cross-linking biotinylated echicetin with avidin. These data indicate that clustering of GPIb alone is sufficient to activate platelets. In vivo, echicetin probably activates platelets rather than inhibits platelet activation, as previously proposed, accounting for the observed induction of thrombocytopenia.
authors: Theodor Kocher Institute, University of Berne, Switzerland.
authors: A
authors: A
authors: Navdaev
authors: D
authors: D
authors: Dörmann
authors: J M
authors: JM
authors: Clemetson
authors: K J
authors: KJ
authors: Clemetson
mesh_terms: D000085:Acetates / Q000494:pharmacology; D000818:Animals; D001241:Aspirin / Q000494:pharmacology; D001360:Avidin / Q000494:pharmacology; D001665:Binding Sites; D019921:Biotinylation; D001798:Blood Proteins / Q000378:metabolism; D002352:Carrier Proteins; D002614:Chelating Agents / Q000494:pharmacology; D004492:Edetic Acid / Q000494:pharmacology; D005340:Fibrinogen / Q000378:metabolism; D007075:Immunoglobulin M / Q000378:metabolism*; D007145:Immunoglobulin kappa-Chains / Q000378:metabolism*; D037102:Lectins / Q000737:chemistry / Q000494:pharmacology; D046911:Macromolecular Substances; D019007:P-Selectin / Q000096:biosynthesis; D010766:Phosphorylation / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000378:metabolism; D011485:Protein Binding; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011506:Proteins / Q000737:chemistry* / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects*; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D014757:Viper Venoms / Q000737:chemistry*
chemical_list: D000085:Acetates; D001798:Blood Proteins; D002352:Carrier Proteins; D002614:Chelating Agents; D007075:Immunoglobulin M; D007145:Immunoglobulin kappa-Chains; D037102:Lectins; D046911:Macromolecular Substances; D019007:P-Selectin; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D011506:Proteins; D014757:Viper Venoms; D001360:Avidin; C080995:echicetin; D014443:Tyrosine; D005340:Fibrinogen; D004492:Edetic Acid; C084062:lamifiban; D011505:Protein-Tyrosine Kinases; D001241:Aspirin