The platelet receptor CLEC-2 is active as a dimer
MetadataShow full item record
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. © 2009 American Chemical Society.
Showing items related by title, author, creator and subject.
Cipolla, L.; Consonni, A.; Guidetti, G.; Canobbio, I.; Okigaki, M.; Falasca, Marco; Ciraolo, E.; Hirsch, E.; Balduini, C.; Torti, M. (2013)Background: The proline-rich tyrosine kinase Pyk2 is a focal adhesion kinase expressed in blood platelets, and is activated downstream of G-protein coupled receptors as well as integrin a2ß1. Objective: In this study we ...
The focal adhesion kinase Pyk2 links Ca2+ signalling to Src family kinase activation and protein tyrosine phosphorylation in thrombin-stimulated plateletsCanobbio, I.; Cipolla, L.; Guidetti, G.; Manganaro, D.; Visconte, C.; Kim, S.; Okigaki, M.; Falasca, Marco; Kunapuli, S.; Torti, M. (2015)In blood platelets, stimulation of G protein-coupled receptors (GPCRs) by thrombin triggers the activation of Src family kinases (SFKs), resulting in the tyrosine-phosphorylation of multiple substrates, but the mechanism ...
Dave, R.; Hume, D.; Elsegood, Caryn; Kellie, S. (2009)In macrophages, tyrosine phosphorylation regulates many signalling pathways leading to growth, differentiation, activation, phagocytosis and adhesion. Protein tyrosine phosphatases (PTPs) represent a biochemical counterbalance ...