Accessibility navigation


CLEC-2 activates Syk through dimerization

Hughes, C. E., Pollitt, A. Y., Mori, J., Eble, J. A., Tomlinson, M. G., Hartwig, J. H., O'Callaghan, C. A., Fütterer, K. and Watson, S. P. (2010) CLEC-2 activates Syk through dimerization. Blood, 115 (14). pp. 2947-2955. ISSN 1528-0020

[img] Text
· Restricted to Repository staff only
· The Copyright of this document has not been checked yet. This may affect its availability.

1MB

It is advisable to refer to the publisher's version if you intend to cite from this work. See Guidance on citing.

To link to this item DOI: 10.1182/blood-2009-08-237834

Abstract/Summary

The C-type lectin receptor CLEC-2 activates platelets through Src and Syk tyrosine kinases, leading to tyrosine phosphorylation of downstream adapter proteins and effector enzymes, including phospholipase-C gamma2. Signaling is initiated through phosphorylation of a single conserved tyrosine located in a YxxL sequence in the CLEC-2 cytosolic tail. The signaling pathway used by CLEC-2 shares many similarities with that used by receptors that have 1 or more copies of an immunoreceptor tyrosine-based activation motif, defined by the sequence Yxx(L/I)x(6-12)Yxx(L/I), in their cytosolic tails or associated receptor chains. Phosphorylation of the conserved immunoreceptor tyrosine-based activation motif tyrosines promotes Syk binding and activation through binding of the Syk tandem SH2 domains. In this report, we present evidence using peptide pull-down studies, surface plasmon resonance, quantitative Western blotting, tryptophan fluorescence measurements, and competition experiments that Syk activation by CLEC-2 is mediated by the cross-linking through the tandem SH2 domains with a stoichiometry of 2:1. In support of this model, cross-linking and electron microscopy demonstrate that CLEC-2 is present as a dimer in resting platelets and converted to larger complexes on activation. This is a unique mode of activation of Syk by a single YxxL-containing receptor.

Item Type:Article
Refereed:Yes
Divisions:Faculty of Life Sciences > School of Biological Sciences > Biomedical Sciences
ID Code:44577
Publisher:American Society of Hematology

University Staff: Request a correction | Centaur Editors: Update this record

Page navigation