The platelet receptor CLEC-2 is active as a dimer

Aleksandra A. Watson, Charita M. Christou, John R. James, Angharad E. Fenton-May, Gerald E. Moncayo, Anita R. Mistry, Simon J. Davis, Robert J C Gilbert, Aron Chakera, Chris A. O'Callaghan

Research output: Contribution to journalArticlepeer-review


The platelet receptor CLEC-2 binds to the snake venom toxin rhodocytin and the tumor cell surface protein podoplanin. Binding of either of these ligands promotes phosphorylation of a single tyrosine residue in the YXXL motif in the intracellular domain of CLEC-2. Phosphorylation of this tyrosine initiates binding of spleen tyrosine kinase (Syk) and triggers further downstream signaling events and ultimately potent platelet activation and aggregation. However, it is unclear how a single YXXL motif can interact efficiently with Syk, which usually recognizes two tandem YXXL repeats presented as an immunoreceptor tyrosine-based activation motif (ITAM). Using bioluminescence resonance energy transfer, coimmuno-preciptitation, recombinant protein expression and analytical gel filtration chromatography, surface plasmon resonance, Western blotting, multiangle light scattering (MALS), and analytical ultracentrifugation, we show that CLEC-2 exists as a non-disulfide-linked homodimer which could alloweach Syk molecule to interact with two YXXL motifs, one from each CLEC-2 monomer.

Original languageEnglish
Pages (from-to)10988-10996
Number of pages9
Issue number46
Publication statusPublished - 24 Nov 2009


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