GALECTIN-3 IS A NOVEL SUBSTRATE FOR HUMAN MATRIX METALLOPROTEINASE-2 AND METALLOPROTEINASE-9

The primary structure of galectin-3, a similar to 30 kDa galactoside-b inding protein (aka CBP-35, mL-34, hL-31, L-29, Mac-2, and epsilon BP) , reveals two structural domains: an amino-terminal domain consists of a Pro-Gly-rich motif, and a globular carboxyl-terminal domain contain ing a carbohydrate-binding site. In this study, we report that the ami no-terminal domain of galectin-3 contains a cleavage site for two memb ers of the matrix metalloproteinase family of enzymes: the 72 kDa (gel atinase A, MMP-2) and the 92 kDa (gelatinase B, MMP-9) proteinases. Th e major cleavage site for the gelatinases in galectin-3 is at the Ala( 62)-Tyr(63) bond, and its hydrolysis by these enzymes was inhibited by TIMP-2. Cell-surface expression of galectin-3 was reduced following t reatment of viable T47D human breast carcinoma cells with gelatinase A . These results suggest that galectin-3 may be a substrate for gelatin ases and that its degradation may play a role in modulating the biolog ical activities of galectin-3.