MODULATION OF THE BIOLOGICAL FUNCTIONS OF GALECTIN-3 BY MATRIX METALLOPROTEINASES

Galectin-3 is an important intracellular and extracellular lectin whic h is presumed to interact with extracellular matrix proteins and cell surface glycoproteins in normal and pathophysiological conditions. The exact physiological role of the protein is presently not known. We ha ve previously demonstrated that recombinant human galectin-3 is a nove l substrate for metalloproteinases, particularly MMP-2 and MMP-9. Thes e enzymes are capable of efficiently cleaving the Ala(62)-Tyr(63) bond of the ca. 30 kDa galectin-3, generating a 22 kDa fragment with intac t carbohydrate recognition domain and a ca. 9 kDa polypeptide comprisi ng the amino terminal end of the intact galectin-3. in this study, we analyzed interactions of the 22 kDa fragment of galectin-3 with immobi lized laminins. We have also compared the hemagglutination as well as homodimerization potentials of this fragment with that of intact galec tin-3. Our data suggest that cleavage of galectin-3 by metalloproteina ses; (a) alters the carbohydrate recognition domain of the lectin so t hat it binds more tightly to the glycoconjugates and, (b) reduces self association of the galectin molecules thereby abrogating the biologica l properties dependent on such associations or homodimerization. (C) 1 998 Elsevier Science B.V.