Platelet receptors activated via mulitmerization: glycoprotein VI, GPIb-IX-V, and CLEC-2.

While very different in structure, GPVI - the major collagen receptor on platelet membranes, the GPIb-IX-V complex - the receptor for von Willebrand factor, and CLEC-2, a novel platelet activation receptor for podoplanin, share several common features in terms of function and platelet activation signal transduction pathways. All employ Src family kinases (SFK), Syk, and other signaling molecules involving tyrosine phosphorylation, similar to those of immunoreceptors for T and B cells. There appear to be overlapping functional roles for these glycoproteins, and in some cases, they can compensate for each other, suggesting a degree of redundancy. New ligands for these receptors are being identified, which broadens their functional relevancy. This is particularly true for CLEC-2, whose functions beyond hemostasis are being explored. The common mode of signaling, clustering, and localization to glycosphingolipid-enriched microdomains (GEMs) suggest that GEMs are central to signaling function by ligand-dependent association of these receptors, SFK, Syk, phosphotyrosine phosphatases, and other signaling molecules.