RRC ID 43034
Author Suzuki-Inoue K, Kato Y, Inoue O, Kaneko MK, Mishima K, Yatomi Y, Yamazaki Y, Narimatsu H, Ozaki Y.
Title Involvement of the snake toxin receptor CLEC-2, in podoplanin-mediated platelet activation, by cancer cells.
Journal J Biol Chem
Abstract Podoplanin (aggrus), a transmembrane sialoglycoprotein, is involved in tumor cell-induced platelet aggregation, tumor metastasis, and lymphatic vessel formation. However, the mechanism by which podoplanin induces these cellular processes including its receptor has not been elucidated to date. Podoplanin induced platelet aggregation with a long lag phase, which is dependent upon Src and phospholipase Cgamma2 activation. However, it does not bind to glycoprotein VI. This mode of platelet activation was reminiscent of the snake toxin rhodocytin, the receptor of which has been identified by us as a novel platelet activation receptor, C-type lectin-like receptor 2 (CLEC-2) (Suzuki-Inoue, K., Fuller, G. L., Garcia, A., Eble, J. A., Pohlmann, S., Inoue, O., Gartner, T. K., Hughan, S. C., Pearce, A. C., Laing, G. D., Theakston, R. D., Schweighoffer, E., Zitzmann, N., Morita, T., Tybulewicz, V. L., Ozaki, Y., and Watson, S. P. (2006) Blood 107, 542-549). Therefore, we sought to evaluate whether CLEC-2 serves as a physiological counterpart for podoplanin. Association between CLEC-2 and podoplanin was confirmed by flow cytometry. Furthermore, their association was dependent on sialic acid on O-glycans of podoplanin. Recombinant CLEC-2 inhibited platelet aggregation induced by podoplanin-expressing tumor cells or lymphatic endothelial cells, suggesting that CLEC-2 is responsible for platelet aggregation induced by endogenously expressed podoplanin on the cell surfaces. These findings suggest that CLEC-2 is a physiological target protein of podoplanin and imply that it is involved in podoplanin-induced platelet aggregation, tumor metastasis, and other cellular responses related to podoplanin.
Volume 282(36)
Pages 25993-6001
Published 2007-9-7
DOI 10.1074/jbc.M702327200
PII M702327200
PMID 17616532
MeSH Animals CHO Cells Cell Line, Tumor Cricetinae Cricetulus Endothelial Cells / metabolism Enzyme Activation / drug effects Gene Expression Regulation, Neoplastic / drug effects Humans Lectins, C-Type / metabolism* Membrane Glycoproteins / metabolism* Membrane Glycoproteins / pharmacology Mice Mice, Transgenic N-Acetylneuraminic Acid / metabolism Neoplasm Metastasis Neoplasms / metabolism* Phospholipase C gamma / metabolism Platelet Aggregation* / drug effects Polysaccharides / metabolism Recombinant Proteins Viper Venoms / metabolism Viper Venoms / pharmacology src-Family Kinases / metabolism
IF 4.238
Times Cited 271
Human and Animal Cells