Tyrosine-phosphorylated galectin-3 protein is resistant to prostate-specific antigen (PSA) cleavage.

Abstract

Galectin-3 is a chimeric carbohydrate-binding protein, which interacts with cell surface carbohydrate-containing molecules and extracellular matrix glycoproteins and has been implicated in various biological processes such as cell growth, angiogenesis, motility, and metastasis. It is expressed in a wide range of tumor cells and is associated with tumor progression. The functions of galectin-3 are dependent on its localization and post-translational modifications such as cleavage and phosphorylation. Recently, we showed that galectin-3 Tyr-107 is phosphorylated by c-Abl; concomitantly, it was also shown that galectin-3 can be cleaved at this site by prostate-specific antigen (PSA), a chymotrypsin-like serine protease, after Tyr-107, resulting in loss of galectin-3 multivalency while preserving its carbohydrate binding activity. Galectin-3 is largely a monomer in solution but may form a homodimer by self-association through its carbohydrate recognition domain, whereas, in the presence of a ligand, galectin-3 polymerizes up to pentamers utilizing its N-terminal domain. Oligomerization is a unique feature of secreted galectin-3, which allows its function by forming ordered galectin-glycan structures, i.e. lattices, on the cell surface or through direct engagement of specific cell surface glycoconjugates by traditional ligand-receptor binding. We questioned whether Tyr-107 phosphorylation by c-Abl affects galectin-3 cleavage by PSA. The data suggest a role for galectin-3 in prostate cells associated with increased activity of c-Abl kinase and loss of phosphatase and tensin homologue deleted on chromosome 10 (PTEN) activity. In addition, the ratio of phosphorylated/dephosphorylated galectin-3 might be used as a complementary value to that of PSA for prognosis of prostate cancer and a novel therapeutic target for the treatment of prostate cancer.

• Authors: Vitaly Balan, Pratima Nangia-Makker, Dhong Hyo Kho, Yi Wang, Avraham Raz
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 287 Issue 8 Pg. 5192-8 (Feb 17 2012) ISSN: 1083-351X [Electronic] United States
• PMID: 22232548 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Galectin 3
• Tyrosine
• Proto-Oncogene Proteins c-abl
• Phosphoric Monoester Hydrolases
• PTEN Phosphohydrolase
• Prostate-Specific Antigen

Topics

• Cell Line, Tumor
• Chemotaxis
• Extracellular Space (metabolism)
• Galectin 3 (chemistry, metabolism)
• Humans
• Models, Molecular
• Neovascularization, Pathologic (metabolism)
• PTEN Phosphohydrolase (metabolism)
• Phosphoric Monoester Hydrolases (metabolism)
• Phosphorylation
• Prostate-Specific Antigen (metabolism)
• Protein Conformation
• Proteolysis
• Proto-Oncogene Proteins c-abl (metabolism)
• Tyrosine (metabolism)