J. Ochieng et al., MODULATION OF THE BIOLOGICAL FUNCTIONS OF GALECTIN-3 BY MATRIX METALLOPROTEINASES, Biochimica et biophysica acta (G). General subjects, 1379(1), 1998, pp. 97-106
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.