Thrombomodulation via CLEC-2 targeting.
CLEC-2 is a C-type lectin-like molecule that has recently been identified as a receptor on the surface of platelets. Ligand binding by CLEC-2 promotes phosphorylation of a tyrosine in the cytoplasmic domain YXXL motif of CLEC-2 by Src kinases and further downstream signalling events trigger platelet activation and aggregation. The snake venom protein rhodocytin and the endogenous protein podoplanin have been identified as ligands. The structures of CLEC-2 and rhodocytin suggest that ligand binding could cluster CLEC-2 molecules at the platelet surface, so initiating signalling. CLEC-2 is a promising target for therapeutic strategies to inhibit platelet activity in thrombotic vascular disease.
O'Callaghan
Chris A
CA
Henry Wellcome Building for Molecular Physiology, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK. chris.ocallaghan@ndm.ox.ac.uk
D000818:Animals; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology; D016503:Drug Delivery Systems; D006801:Humans; D037181:Lectins, C-Type / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology; D008958:Models, Molecular; D015539:Platelet Activation / Q000187:drug effects / Q000502:physiology; D013927:Thrombosis / Q000188:drug therapy*; D014757:Viper Venoms / Q000737:chemistry / Q000494:pharmacology; D000098853:Podoplanin
D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D014757:Viper Venoms; C104778:CLEC2B protein, human; C117468:PDPN protein, human; D000098853:Podoplanin; C112292:rhodocytin protein, Calloselasma rhodostoma