Modulation of the biological functions of galectin-3 by matrix metalloproteinases

Biochim Biophys Acta. 1998 Jan 8;1379(1):97-106. doi: 10.1016/s0304-4165(97)00086-x.

Abstract

Galectin-3 is an important intracellular and extracellular lectin which 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 have previously demonstrated that recombinant human galectin-3 is a novel substrate for metalloproteinases, particularly MMP-2 and MMP-9. These enzymes are capable of efficiently cleaving the Ala62-Tyr63 bond of the ca. 30 kDa galectin-3, generating a 22 kDa fragment with intact carbohydrate recognition domain and a ca. 9 kDa polypeptide comprising the amino terminal end of the intact galectin-3. In this study, we analyzed interactions of the 22 kDa fragment of galectin-3 with immobilized laminins. We have also compared the hemagglutination as well as homodimerization potentials of this fragment with that of intact galectin-3. Our data suggest that cleavage of galectin-3 by metalloproteinases; (a) alters the carbohydrate recognition domain of the lectin so that it binds more tightly to the glycoconjugates and, (b) reduces selfassociation of the galectin molecules thereby abrogating the biological properties dependent on such associations or homodimerization.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigens, Differentiation / chemistry
  • Antigens, Differentiation / metabolism*
  • Binding Sites
  • Cell Line
  • Collagenases / metabolism
  • Dimerization
  • Electrophoresis, Polyacrylamide Gel
  • Galectin 3
  • Gelatinases / metabolism
  • Hemagglutination
  • Humans
  • Immunoblotting
  • Laminin / metabolism
  • Lectins / metabolism
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9
  • Metalloendopeptidases / metabolism*
  • Mice
  • Peptide Fragments / metabolism
  • Peptide Fragments / pharmacology
  • Protein Binding
  • Recombinant Proteins / metabolism

Substances

  • Antigens, Differentiation
  • Galectin 3
  • Laminin
  • Lectins
  • Peptide Fragments
  • Recombinant Proteins
  • Collagenases
  • Gelatinases
  • Metalloendopeptidases
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9