Galectin-3 is a novel substrate for human matrix metalloproteinases-2 and -9.
The primary structure of galectin-3, a approximately 30 kDa galactoside-binding 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 containing a carbohydrate-binding site. In this study, we report that the amino-terminal domain of galectin-3 contains a cleavage site for two members of the matrix metalloproteinase family of enzymes: the 72 kDa (gelatinase A, MMP-2) and the 92 kDa (gelatinase B, MMP-9) proteinases. The major cleavage site for the gelatinases in galectin-3 is at the Ala62-Tyr63 bond, and its hydrolysis by these enzymes was inhibited by TIMP-2. Cell-surface expression of galectin-3 was reduced following treatment of viable T47D human breast carcinoma cells with gelatinase A. These results suggest that galectin-3 may be a substrate for gelatinases and that its degradation may play a role in modulating the biological activities of galectin-3.
Ochieng
J
J
Metastasis Research Program, Michigan Cancer Foundation, Detroit 48201.
Fridman
R
R
Nangia-Makker
P
P
Kleiner
D E
DE
Liotta
L A
LA
Stetler-Stevenson
W G
WG
Raz
A
A
D000595:Amino Acid Sequence; D000943:Antigens, Differentiation / Q000737:chemistry / Q000378:metabolism*; D001665:Binding Sites; D001943:Breast Neoplasms / Q000378:metabolism; D050260:Carbohydrate Metabolism; D017364:Collagenases / Q000378:metabolism*; D037502:Galectin 3; D018093:Gelatinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006801:Humans; D006868:Hydrolysis; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D061965:Matrix Metalloproteinase Inhibitors; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008969:Molecular Sequence Data; D011506:Proteins / Q000494:pharmacology; D013379:Substrate Specificity; D019716:Tissue Inhibitor of Metalloproteinase-2; D014407:Tumor Cells, Cultured
D000943:Antigens, Differentiation; D037502:Galectin 3; D061965:Matrix Metalloproteinase Inhibitors; D011506:Proteins; D019716:Tissue Inhibitor of Metalloproteinase-2; D017364:Collagenases; D018093:Gelatinases; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9