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Glycobiology Advance Access originally published online on July 25, 2006
Glycobiology 2006 16(11):15C-20C; doi:10.1093/glycob/cwl028
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© The Author 2006. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

COMMUNICATION

Galectin-8 and galectin-9 are novel substrates for thrombin

Nozomu Nishi1,2, Aiko Itoh4, Hiroki Shoji2, Hiroshi Miyanaka3 and Takanori Nakamura2

2 Department of Endocrinology, 3 Life Science Research Center, Kagawa University, 1750–1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761–0793, Japan; and 4 GalPharma Co., Ltd., 2217–44 Hayashimachi, Takamatsu, Kagawa 761–0301, Japan


1 To whom correspondence should be addressed; e-mail: nnishi{at}med.kagawa-u.ac.jp

Received on June 5, 2006; revised on July 19, 2006; accepted on July 23, 2006

Galectin-8 and galectin-9, which each consist of two carbohydrate recognition domains (CRDs) joined by a linker peptide, belong to the tandem-repeat-type subclass of the galectin family. Alternative splicing leads to the formation of at least two and three distinct splice variants (isoforms) of galectin-8 and galectin-9, respectively, with tandem-repeat-type structures. The isoforms share identical CRDs and differ only in the linker region. In a search for differences in biological activity among the isoforms, we found that their isoforms with the longest linker peptide, that is, galectin-8L and galectin-9L (G8L and G9L), are highly susceptible to thrombin cleavage, whereas the predominant isoforms, galectin-8M and galectin-9M (G8M and G9M), and other members of human galectin family so far examined were resistant to thrombin. Amino acid sequence analysis of proteolytic fragments and site-directed mutagenesis showed that the thrombin cleavage sites (-IAPRT- and –PRPRG- for G8L and G9L, respectively) resided within the linker peptides. Although intact G8L stimulated neutrophil adhesion to substrate more efficiently than G8M, the activity of G8L but not that of G8M decreased on thrombin digestion. Similarly, thrombin treatment almost completely abolished eosinophil chemoattractant (ECA) activity of G9L. These observations suggest that G8L and G9L play unique roles in relation to coagulation and inflammation.

Key words: galectin / linker peptide / proteolysis / thrombin


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