The platelet receptor CLEC-2 is active as a dimer
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 ini...
| Main Authors: | , , , , , , , , , |
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| Format: | Journal Article |
| Published: |
American Chemical Society
2009
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| Online Access: | http://hdl.handle.net/20.500.11937/4827 |
| _version_ | 1848744625743855616 |
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| author | Watson, A. Christou, C. James, J. Fenton-May, A. Moncayo, G. Mistry, A. Davis, S. Gilbert, R. Chakera, Aron O'Callaghan, C. |
| author_facet | Watson, A. Christou, C. James, J. Fenton-May, A. Moncayo, G. Mistry, A. Davis, S. Gilbert, R. Chakera, Aron O'Callaghan, C. |
| author_sort | Watson, A. |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | 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. |
| first_indexed | 2025-11-14T06:04:27Z |
| format | Journal Article |
| id | curtin-20.500.11937-4827 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T06:04:27Z |
| publishDate | 2009 |
| publisher | American Chemical Society |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-48272017-09-13T14:46:23Z The platelet receptor CLEC-2 is active as a dimer Watson, A. Christou, C. James, J. Fenton-May, A. Moncayo, G. Mistry, A. Davis, S. Gilbert, R. Chakera, Aron O'Callaghan, C. 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. 2009 Journal Article http://hdl.handle.net/20.500.11937/4827 10.1021/bi901427d American Chemical Society restricted |
| spellingShingle | Watson, A. Christou, C. James, J. Fenton-May, A. Moncayo, G. Mistry, A. Davis, S. Gilbert, R. Chakera, Aron O'Callaghan, C. The platelet receptor CLEC-2 is active as a dimer |
| title | The platelet receptor CLEC-2 is active as a dimer |
| title_full | The platelet receptor CLEC-2 is active as a dimer |
| title_fullStr | The platelet receptor CLEC-2 is active as a dimer |
| title_full_unstemmed | The platelet receptor CLEC-2 is active as a dimer |
| title_short | The platelet receptor CLEC-2 is active as a dimer |
| title_sort | platelet receptor clec-2 is active as a dimer |
| url | http://hdl.handle.net/20.500.11937/4827 |