Abstract
Previous work has demonstrated the ability of the NG2 proteoglycan, a component of microvascular pericytes, to stimulate endothelial cell motility and morphogenesis. This function of NG2 depends on formation of a complex with galectin-3 and α3β1 integrin to stimulate integrin-mediated transmembrane signaling. In addition, the co-expression of galectin-3 and NG2 in A375 melanoma cells suggests that the malignant properties of these cells may be affected by interaction between the two molecules. Here, we extend the theme of co-expression and interaction of NG2 and galectin-3 to human glioma cells. We also establish a molecular basis for the NG2/galectin-3 interaction. The C-terminal carbohydrate recognition domain of galectin-3 is responsible for binding to the NG2 core protein. Within the NG2 extracellular domain, the membrane-proximal D3 segment of the proteoglycan contains the primary binding site for interaction with galectin-3. The interaction between galectin-3 and NG2 is a carbohydrate-dependent one mediated by N-linked rather than O-linked oligosaccharides within the D3 domain of the NG2 core protein. These studies establish a foundation for attempts to reduce the aggressive properties of tumor cells by disrupting the NG2/galectin-3 interaction.
Original language | English (US) |
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Pages (from-to) | 115-127 |
Number of pages | 13 |
Journal | Journal of cellular biochemistry |
Volume | 98 |
Issue number | 1 |
DOIs | |
State | Published - May 1 2006 |
Externally published | Yes |
Keywords
- Carbohydrate-dependent protein-protein interaction
- Galectin-3
- Glioma
- Glycosylation
- NG2
ASJC Scopus subject areas
- Biochemistry
- Molecular Biology
- Cell Biology