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J. Biol. Chem., Vol. 283, Issue 15, 10109-10123, April 11, 2008

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Galectin-1, -2, and -3 Exhibit Differential Recognition of Sialylated Glycans and Blood Group Antigens^*

Sean R. Stowell, Connie M. Arthur, Padmaja Mehta, Kristen A. Slanina, Ola Blixt^¶, Hakon Leffler^||, David F. Smith, and Richard D. Cummings¹

From the Department of Biochemistry, Emory University School of Medicine, Atlanta, Georgia 30322, Cardiovascular Biology, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma 73104, ^¶Carbohydrate Synthesis and Protein Expression Core Resource, Consortium for Functional Glycomics, Department of Molecular Biology, Scripps Research Institute, La Jolla, California 92037, and the ^||Section of Microbiology Immunology and Glycobiology, Lund University, 223 62 Lund, Sweden

Human galectins have functionally divergent roles, although most of the members of the galectin family bind weakly to the simple disaccharide lactose (Galβ1-4Glc). To assess the specificity of galectin-glycan interactions in more detail, we explored the binding of several important galectins (Gal-1, Gal-2, and Gal-3) using a dose-response approach toward a glycan microarray containing hundreds of structurally diverse glycans, and we compared these results to binding determinants on cells. All three galectins exhibited differences in glycan binding characteristics. On both the microarray and on cells, Gal-2 and Gal-3 exhibited higher binding than Gal-1 to fucose-containing A and B blood group antigens. Gal-2 exhibited significantly reduced binding to all sialylated glycans, whereas Gal-1 bound 2-3- but not 2-6-sialylated glycans, and Gal-3 bound to some glycans terminating in either 2-3- or 2-6-sialic acid. The effects of sialylation on Gal-1, Gal-2, and Gal-3 binding to cells also reflected differences in cellular sensitivity to Gal-1-, Gal-2-, and Gal-3-induced phosphatidylserine exposure. Each galectin exhibited higher binding for glycans with poly-N-acetyllactosamine (poly(LacNAc)) sequences (Galβ1-4GlcNAc)_n when compared with N-acetyllactosamine (LacNAc) glycans (Galβ1-4GlcNAc). However, only Gal-3 bound internal LacNAc within poly(LacNAc). These results demonstrate that each of these galectins mechanistically differ in their binding to glycans on the microarrays and that these differences are reflected in the determinants required for cell binding and signaling. The specific glycan recognition by each galectin underscores the basis for differences in their biological activities.

Received for publication, November 21, 2007 , and in revised form, January 22, 2008.

^* This work was supported by National of Institutes of Health Grant HL085607, by resources from the Consortium for Functional Glycomics (Core D and Core H) funded by NIGMS Grant GM62116 from the National Institutes of Health, and by Swedish Research Council Grant 15390 (to H. L.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ To whom correspondence should be addressed. Tel.: 404-727-5962; Fax: 404-727-2738; E-mail: rdcummi{at}emory.edu.

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